Physiological responses of dairy animals to recombinant bovine somatotropin : A review

Recombinant bovine somatotropins (rbST) have been synthesized and manufactured using recombinant DNA (rDNA) techniques. The rbST has increased milk production in dairy animals, including cow, sheep and goats. There are management factors including dosage of rbST, injection interval, genetic potential and environmental conditions which affect the magnitude of the animal-response to rbST. For dairy cows, the optimal dose of rbST treatment is between 25 and 50 mg/day. Daily injection of rbST may produce better response, but sustained-release formulations of rbST are more practical. The magnitude of milk production response to rbST range from 10 to 35% in dairy cows. The rbST has no or little effects on the milk composition, processing properties and taste. The rbST did not affect digestion of feeds or the efficiency of utilizing absorbed nutrients for milk synthesis, and it has no or little effect on rumen fermentation, flow of nutrients to the small intestine and total tract digestibility, but it improves the feed efficiency in dairy cows. The rbST induced significant increase in serum bST. It has a galactopoietic effect, since it increase the metabolic activity of mammary cells or slow their involution, thereby allowing more secretory cells to persist over time and contribute to increasing milk synthesis and yield. It has a great impact on mammary gland development and subsequently milk-producing capacity in dairy heifers. The rbST increase the hypothyroid status of lactating cows and maintain euthyroid condition in the mammry gland, thus enhancing its metabloic priority. The rbST did not adversely affect reproduction, and the observed decreases in reproductive performance in rbST-treated cows may be attributed more to the increases in milk yield than to direct effect of rbST. The increased production responses to rbST in heat-stressed dairy cows is less than that under more moderate conditions. The incidence of mastitis in rbST-treated cows is due more to increased milk yield than to any direct effects of rbST. The rbST was efficacious in increasing milk yields in sheep and goats without adverse effects.


INTRODUCTION
Bovine somatotropin (bST) is naturally-occuring protein produced by the pituitary gland in all cattle.Recombinant bovine somatotropins (rbST), which differ from their native form by several amino acids, have been synthesized and manufactured using recombinant DNA techniques to increase milk production in dairy cows.The Food and Drug Administration (FDA) approved rbST product in 1993 after determining that its use would be safe and effective.Part of FDA's safety evaluation was to ensure that milk from treated cows was safe for human food.U.S. commercial use began in 1994, and adoption has been extensive.The safety of rbST was evaluated by the American Medical Association, American Academy of Pediatrics, American Cancer Society, Council on Agricultural Science and Technology, Food and Nutrition Science Alliance, Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO).Without exception, all of the medical associations and scientific societies concluded that use of rbST represented no health or safety concerns for consumers or cows.Biomarker-based screening for rbST can be considered a very promising start for detecting rbST abuse in dairy cows.Development of a flow cytometric immunoassay for rbSTinduced antibodies in serum of dairy cows is considered as an important biomarker for pinpointing at rbST abuse in cattle (Smits et al., 2012).In addition, the osteocalcinanti-rbST antibodies combination represents fit-forpurpose biomarkers for screening of rbST abuse in dairy cattle.This screening method can be incorporated in routine veterinary monitoring programmes in the European Union for detection of rbST abuse and in the control of rbST-free dairy farms in the United States of America and other countries (Ludwig et al., 2012).The hormonal induction of lactation in barren high-yielding cows is a reliable, practical and affordable technique in countries where rbST treatment of dairy cows is legally permitted (Mellado et al., 2011).Use of rbST in dairy cows is an excellent example of the development and integration of basic research derived from several fields into a new management practice that can influence the efficiency and profitability of milk production without adversely affecting milk quality or animal health (Phillips, 1996), and have less negative effects on the environment than conventional dairying (Capper et al., 2008).Most research has been with Holsteins, but milk production responses have been reported for all dairy breeds examined including North American and Eurpean breeds (Bauman, 1992), South American breeds (Mattos et al., 1989) and African breeds (Madakaze et al., 1990).In this review article, the mechanistic aspects involved in the physiological responses of dairy animals to rbST in relation to their productive and reproductive performances was focused on and discussed.

Effect of rbST on milk production
Use of rbST treatments has increased milk production in all dairy breeds examined, including Bos indicus cows (Phipps et al., 1991).Most of studies were conducted for one lactation or less, however, an important consideration for the commercial application of rbST is the milk yield response over multiple lactations (Phillips, 1996).So, many studies have evaluated the response to rbST for 2 or more lactations.The rbST-induced increases in milk yield were reported to be maintained for two consecutive lactations (Phipps et al., 1990) or over four lactations (Huber et al., 1991).Management factors have been identified as major source of variation in the magnitude of dairy cows responses to rbST (Bauman, 1992).These factors include dosage of rbST, injection interval, genetic potential and environmental conditions.According to Phillips (1996), cows that are better managed are known to have a greater response to rbST than poorly managed, and producers that manage their operation to maximize milk production have the greatest potential to maximize milk yield response to rbST.For dairy cows, the optimal dose of rbST treatment as a galactopoietic agent is between 25 and 50 mg/day (Downer et al., 1993;Phillips, 1996).Given an adequate dosage, increasing the milk yield in response to rbST was maintained by following the rbST administration daily and every 7, 14 or 28 days (Zinn et al., 1993;Chalupa et al., 1996).Low doses of rbST (10.2 mg/day) in the transition period resulted in higher postpartum body weight, quicker recovery of body condition during lactation, and significantly more milk during treatment (Gulay et al., 2003).
Although, rbST daily injection may produce better response (Bauman, 1992), administration of sustainedrelease formulations of rbST are more practical (Fernandez et al., 1995).However, the increase in milk yield with sustained-release formulations of rbST within a single injection interval will vary (Zinn et al., 1993).That is, following each injection, the milk yield will increase to a peak, approximately at the mid-point of the injection interval, and then decline until the next injection (Phillips, 1996).
Some studies indicated that the rbST-induced milk production was accompanied by altering plasma factors.For example, Gallo and Bloke (1990) working on multiparous cows receiving rbST 350 mg/14 days from 98 to 305 days postpartum, found that milk yield was increased by 20.4 and 3.5% FCM yield by 16.7%.Also, rbST decreased blood pH and buffer capacity by decreasing bicarbonate without affecting blood pressures of O 2 and CO 2 .Plasma albumin was decreased while plasma glucose, insulin and non-etherified fatty acids (NEFA), were increased with rbST treatment at 500 mg/14 days (Flores et al., 2007).However, Abdel-Rahman et al. (2010) found a non-significant increase in serum insulin accompanied by a remarkable drop in serum glucose in primiparous cows that received 250 and 500 mg rbST and multiparous cows injected with 500 mg rbST/14 days.A possible explanation of such hyperinsulinemia accompanied by hypoglycemia is claimed by Gong et al. (1997) who stated that the action of bST may be mediated by increase synthesis and secretion of IGF-1 and insulin.They also showed no significant change in the activity of aspartate aminotrans-ferase (AST) and alanine aminotransferase (ALT) and the level of creatinine in all rbST-treated groups.The activities of serum ALT and AST which are commonly used as indicator of liver cell damage and death were not affected by treatment with rbST.Plasma total protein, cortisol, total lipids, triacylglycerol contents, AST, hemoglobin and packed cell volume were not affected by rbST, but the percentage of triacylglycerol in total lipids was increased with rbST.However, serum total lipids, triglycerides and cholesterol showed a non significant increase in multiparous cows given 500 mg rbST/14 days (Abdel-Rahman et al., 2010).It was claimed that somatotropin mobilizes large quantities of free fatty acids from adipose tissues to be used to supply most of the energy of the body, thus somatotropin acts as a potent carbohydrate and protein sparer (Kannan, 1987).Gallo and Bloke (1990) suggested that rbST had lipolytic and diabetogenic activities and those effects may be important for the increase in nutrient partitioning towards the mammary glands elicited by rbST.
As far as stage of lactation is concerned, studies that compared the effect of rbST at various periods of lactation showed that milk production responses to rbST is proportionately greater later in lactation than earlier (prior to day 60) (Phillips, 1996).In addition, Chalupa et al. (1996), working on dairy cows during weeks 5 through 43 of lactation, showed that the FCM production increased (P<0.05) with 10.3, 20.6 or 41.2 mg/day during week 4 to 36 of rbST treatment.During the final 4 weeks of lactation, 10.3 and 41.2 mg/day of rbST, but not 20.6 mg/day, promoted increase in FCM production (P<0.05).Administration of rbST prior to peak production in cows that are well fed, prevents the number of mammary cells from decreasing, and increases the amount of nutrients directed away from fat and toward the mammary cells, leading to an extension of peak milk production (Bauman, 1999).
Since there is a correlation between blood bST concentrations and genetic potential for milk production and/or actual milk production (Kazmar et al., 1990), there may be differences in rbST-induced milk production in cows of different genetic merit (Phillip, 1996).Cows with greater genetic merit may have a greater potential to respond to rbST (Gibson et al., 1992).However, in a study on dairy cows from 2 genetic groups (mated for 20 years to bulls of high or low transmitting ability for milk yield) and given 0, 10.3, 20.6 or 30.9 mg/day rbST from 14 th week after parturition for 30 weeks, the increase in milk, fat and protein yields due to rbST did not differ between genetic groups.Higher, doses of rbST increased milk yield, 4% FCM in a linear fashion (Nytes et al., 1990).

Effect of rbST on milk composition
Several investigators worked on dairy cows and showed that overall milk composition was not affected by rbST Soliman and EL-Barody 3 treatments at 100-780 mg/14 days (Burchard et al., 1990), 29 mg/day (Binelli et al., 1995) or 10.3-41.2mg/day (Chalupa et al., 1996).Also, Phipps et al. (1996) showed no effect of prolonged-release formulation of rbST on milk composition of Holstein cows.Additionally, in early lactating cows that received rbST for 90 days, milk composition was not affected by rbST treatment (Santos et al., 1999).According to Chalupa et al. (1996), the unaffected milk fat, protein and total solids to rbST reflected the high nutrient densities of the diets, because effects of rbST on milk composition seemed to be related to nutritional status.The rbST did not affect milk composition when cows were fed diets containing positive balances of energy and protein (Bauman, 1992).In general, effects of dietary energy and protein on milk fat and protein from rbSTtreated cows were similar to alterations when high producing cows are fed diets that do not provide adequate energy or protein (Chalupa et al., 1996).On the other hand, many studies indicated variable responses in milk composition to rbST treatments.In dairy cows that received rbST at 640 mg/28 days, yields of fat, protein and lactose increased by 21, 18 and 16%, respectively, but there were no significant changes in protein, lactose, Ca, Mg and P in milk (Oldenbroek and Garssen, 1988).
In addition, cows injected with 30 mg of bST/day increased milk fat and lactose concentrations, but protein and fatty acid composition of milk were not affected (French et al., 1990).Also, McGuire et al. (1992) showed an increase in milk fat and total solids due to rbST at dose of 25 mg/day.But, percentage milk fat was not affected by rbST at 10.3 mg/day, while percentage protein was reduced (Austin et al., 1990).Response of milk composition in 10.3, 20.6 or 30.9 mg rbST-treated cows with different genetic merit indicated that yields of milk fat and protein were increased, but fat and protein percentages were unaffected (Nytes et al., 1990).
The increase in milk fat due to rbST treatment could be attributed to the increase in long chain fatty acids from body reserves mobilized when dairy animals were in negative energy balance (McDowell et al., 1988).The reduction in milk protein content with rbST dosages could be due to the increase in milk yields (Fernandez et al., 1995).Given little change in milk composition together with an increase in milk yield, yield of milk components was increased in the same proportion as the yield (Barbano et al., 1992).Evidences indicate that use of rbST in dairy animals has no or little effects on the milk composition, processing properties and taste (Phillips, 1996).

Effects of rbST on feed intake, nutrients digestibility, body weight, milk production efficiency and energy balance
Productive and nutritional performances of dairy cows have been monitored in milk production studies with rbST.Some studies showed no change in feed intakes (FI) of dairy cows in response to rbST at 56-700 mg/14 days (Downer et al., 1993) or at 29 mg/day (Binelli et al., 1995); thereby resulting in increased feed efficiency (FE).Also, Windsryg et al. (1991) working on ruminally fistulated cows at 60 days postpartum injected with 25 mg of rbST/day for 6 weeks, showed that 3.5% FCM and milk production efficiency were increased with rbST treatment while DM intake, ruminal percentages of crude protein (CP), alpha-amino-N, volatile fatty acids (VFA), pH, total tract apparent digestibility of nutrients and cellulolytic bacteria (%) were not affected by rbST, but the total number of rumen protozoa tended to be higher with rbST.However, Santos et al. (1999) observed that early lactating cows that received rbST for 90 days had lower dry matter intake (DMI) during the first 45 days of experiment, but efficiency of feed utilization was increased with rbST while nutrients digestibility was unaffected.Similar observations were reported by Schwab and Kirchgessner (1990) who found that apparent digestibilities of DM, CP, crude fibers (CF), nitrogen-free extract and energy were not altered in dairy cows that received rbST at 640 mg / 28 days for 168 days.Also, efficiency of milk production was improved in cows treated with rbST at 640 or 960 mg /28 days during 3 successive lactations (Oldenbroek and Garssen, 1990).Since, the above-metioned responses to rbST coincided with increased milk production, extra nutrients required for this increased milk yield are thought to come from mobilization of body tissues (Phillips, 1996).
On the other hand, an increase in DMI by 46% due to rbST (500 mg /14 days), and the commencement of the DMI decrease was correlated with the beginning of the decrease in milk production (Moallem et al., 2000).It was apparent that rbST-treated dairy cows gradually increased feed intake to meet increased metabolic demand (Bauman, 1992).According to Chalupa et al. (1996), DMI were increased (P<0.05) by 5.4 and 8.4% for dairy cows injected with 20.6 and 41.2 mg bST/day respectively, in which cows began to increase DMI after 4 weeks of rbST treatment.This increase in DMI coincided with increased milk production.Also, increased FCM production showed that most of the increased DMI accounted for higher milk production.Thus, rbST-treated cows increased DMI in response to increased production in a predictable manner.
When rbST is administered to cows, more nutrients are needed for increased synthesis of milk protein, fat and lactose (Chalupa et al., 1996).Initially, body stores of protein, fatty acids and glycogen may provide additional nutrients, but nutrients for prolonged increases of production are derived from coordinated changes in the metabolism of many tissues and by increased FI (Bauman, 1992).Chapula et al. (1996) also observed that rbST-treated cows produced more (P<0.01)FCM per kg of feed consumed.This result showed an improvement (P<0.01) in apparent feed efficiency (3.5% FCM/DMI) by 10.4, 12.7 and 12.75% with 10.3, 20.6 and 41.2 mg/day of rbST treatments, respectively.
The mechanism by which rbST might improve FE in dairy cows could be discussed in the light of the following observations.Even though, FI increased with rbST treatment, more dietary nutrients were captured in milk (Bauman, 1992).Because rbST did not affect either digestion of feeds or the efficiency of utilizing absorbed nutrients for milk synthesis (Pillips, 1996), and it has no or little effect on rumen fermentation, flow of nutrients to the small intestine and total tract digestibility (Windsryg et al., 1991), there must be other reasons for the improved FE.When cows produce more milk, they usually consume more feed.The absolute maintenance requirements are not changed, but the relative proportion of intake nutrients needed for maintenance is less and the proportion available for milk synthesis is greater (Chapula et al., 1996).Thus, the relative maintenance requirements are diluted as milk production increases (Chapula et al., 1996).In addition, rbST partitions calories to milk production at the expense of body fat (McGuffy et al., 1991).So, rbST increases the capture of dietary nutrients in milk by decreasing the relative proportion of consumed nutrients needed for maintenance and by partitioning nutrients into milk rather than into body reserves (Chapula et al., 1996).Also, as rbST increased, the weight gain of cows decreased, therefore the main effect of rbST decreased body fat reflecting the partitioning of calories by rbST to milk at the expense of fat deposition (Chalupa et al., 1996).Furthermore, Binelli et al. (1995) using primiparous cows that received rbST (29 mg/day) showed no differences in FI and body weight due to rbST treatment.However, energy balance was lower (P<0.05)for rbST-treated than untreated cows.This study indicated that, in the overall process of nutrient partitioning, body weight was not impaired as a consequence of the greater demand for nutrients by the mammary gland in rbST-treated cows.This effect increased mobilization of adipose depots as reflected by decreased body fat and chronic elevation of serum non-estrified fatty acids (Binelli et al., 1995).These changes provide extra energy needed for increasing milk synthesis and lean tissue as observed in lactating primiparous cows (Binelli et al., 1995).In addition, weights of heart, intestine, kidney, liver and lung were greater (P<0.05) for rbST-treated than untreated cows (Binelli et al., 1995).Such increases in organ weights in response to rbST treatment probably play a role in increasing the availability of nutrients to the mammary gland and thereby contribute to the galactopoietic effects of rbST in dairy cows.Since the nutrients digestibility or the efficiency of energy utilization for maintenance or milk synthesis were not altered in rbST-treated dairy cows (Schwab and Kirchgessner, 1990), current nutritional standards for lactating cows remain applicable (Chalupa et al., 1996).The most important aspect of nutrition and rbST treatment is that cows must be fed to maximize milk yield in a given management situation (Pillips, 1996).So, increased dietary protein and energy augmented the milk production responses to rbST at 10.3 mg/day (Austin et al., 1990).

Effect of rbST on somatotropic secretion and axis
The effect of rbST administration on bST secretion from anterior pituitary was examined in dairy cows when compared with the effect of rbGRF (growth releasing factor).In this respect, primiparous Holstein dairy cows received rbGRF (12 mg/day) and rbST (29 mg/day) for 63 days (Binelli et al., 1995).Both rbGRF and rbST increased (P<0.01)serum bST to concentrations of similar magnitude.Somatotropin content (mg) of pituitary glands from rbGRF-or rbST-treated cows were not different but lower (P<0.01)than that of non-treated cows.This support the notion that release of bST from pituitary somatotrphs may have been increased.bST concentrations (mg/g) in pituitary glands and pituitary weight from rbST-treated cows and non-treated were similar.These similarities between rbST-treated and nontreated cows for pituitary weight and bST concentrations suggest that the exogenous bST (rbST) did not inhibit synthesis or release of endogenous bST from anterior pituitary.
Administration of rbST to dairy cows induces several coordinated metabolic changes that subsequently increase milk synthesis.Current believe suggests that insulin-like growth factor (IGF-I) partially mediates rbSTinduced increases in milk production (Vanderkool et al., 1995).The bST can act directly on tissues or act indirectly by causing the release of IGF-I (Chase et al., 1998).So, indirect growth-promoting actions of bST are mediated by IGF-I (Puchala et al., 2001).Indeed, IGF-I levels were increased during rbST administration to lactating cows (Molento et al., 2002).The IGF-I peptide is predominantly synthesized and secreted from the liver in response to bST binding with the hepatic bST receptors (Gluckman et al., 1987).The biological effects of IGF-I are further regulated by specific IGF-binding protein that control access of IGF-I to target tissues and by the abundance of the type-I IGF receptor at the target tissues (McGuire et al., 1992).This cascade of events is referred to as the somatotropic axis.In this respect, Vanderkool et al. (1995) showed that both rbST and bGRF similarly increased serum concentrations of ST in cows, and they also increased serum IGF-I, liver IGF-I mRNA and serum IGF-binding protein-3, but serum IGF-binding protein-2, number of free binding sites for IGF-I in mammary tissues were decreased.In liver, rbST did not alter the abundance of mRNA for ST receptors or the number of free binding sites for ST.So, these results suggest that exogenous bST (rbST) is more effective as an IGF-I secretagogue than endogenous bST.

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Both bGRF and rbST similarly increased milk yield, suggesting that both hormones stimulate milk synthesis mostly through the same mechanism (Vanderkool et al., 1995).Synthesis of IGF-I in liver is regulated, to a great extent, at the level of mRNA abundance.So, the increased synthesis of IGF-I in liver is largely responsible for the increased serum IGF-I in cows treated with rbST.Despite the fact that rbST stimulated the endocrine IGF-I-BP axis more than bGRF, both hormones stimulated milk synthesis similarly.However, Sharma et al. (1994) reported that serum IGF-I and liver IGF-I mRNA were not correlated with milk yield when cows were in early lactation when compared with those in late lactation.Thus, Vanderkool et al. (1995) concluded that the serum IGF-I is not good indicator for the galactopoietics potency of rbST and rbGRF.Otherwise, the galactopoietic's effects of these hormones are not mediated exclusively through the endocrine IGF-I BP axis.Weber et al. (2007) showed that selection for milk yield increased serum bST, prolonged the postpartum reduction in serum IGF-I.According to Collier et al. (2008), plasma IGF-I and IGF-II were increased in lactating cows treated with rbST (25 mg/d), while milk IGF-I and IGF-II was not affected by rbST treatment.They failed to detect an uncoupling of the somatotropin-IGF-I axis in summer despite an induced negative energy balance during thermal stress.

Effect of rbST on mammary gland
The effect of rbST on mammary function was investigated in dairy cattle when compared with the effect of rbGRF (Binelli et al., 1995).Results on dairy cows that received infusion of rbGRF (12 mg/day) or rbST (29 mg/day) for 63 days, showed that neither rGRF nor rbST affected mammary parenchymal weight or total mammary parenchymal DNA.Such observations are consistent with Capuco et al. (1989) who found no changes in mammary DNA of dairy cows in response to rbST.Binelli et al. (1995) also showed that the total RNA, RNA concentrations, RNA accretion and the RNA to DNA ratio increased in the mammary tissues of cows treated with rbGRF or rbST.Total RNA is an index of cell metabolic activity.Therefore, they suggested that rbGRF and rbST increased the secretory capacity of the mammary gland and their actions on galactopoiesis increased synthesis of milk per mammary cell.Gradual involution of the mammary gland, as reflected by decreasing milk yield, arises from the remodeling transition of mammary epithelial cells from secretory to nonsecretory cells.So, the bGRF and bST increase the metabolic activity of mammary cells or slow their involution without affecting mammary cell numbers or mammary remodeling, thereby allowing more secretory cells to persist over time and contribute to increasing milk synthesis and yield (Binelli et al., 1995).Such interpretation may explain in part the galactopoietic effects of bGRF and bST in dairy cows.Carstens et al. (1997) showed that treatment of rbST at 500 mg/14 days in dairy heifers increased (P<0.01) the proportional weight of fat-free mammary parenchymal tissue by 82%, suggesting that rbST had a great impact on mammary gland development and subsequently milkproducing capacity in dairy heifers.

Effect of rbST on thyroid status
Thyroid hormones are important for maintaining normal lactation.Thyroxine (T 4 ), the predominant thyroid hormone in blood circulation, has little inherent biological activity, while triiodothyronine (T 3 ), which is produced by enzymatic 5'-deiodination of T 4 within the thyroid gland, is the most biologically active thyroid hormone (Hadley, 1992).So, the extra-thyroidal activity of 5'-deiodinase (5'D) is an important control to regulate thyroid status of animal tissues in various physiological and pathological situations.Nevertheless, lactating cows are often in a functional hypothyroid state, which is characterized by lower concentrations of circulating iodothyronine and higher concentrations of thyroid-stimulating hormone than those of nonlactating cows.A positive relationship between 5'D activity in the mammary gland and milk yield was reported for rbST-treated cows (Capuco et al., 1989).Short-term administration of bST (40 mg/day) for 5 days to cows in late lactation increased milk yield was accompanied by increased 5'D activity in mammary tissues without changes in 5'D activity in liver and kidney or in the concentrations of serum T 3 and T 4 , suggesting that the regulation of extrathyroidal activity of 5'D is also important in lactating cows to permit or mediate the animal galactopoietic responses to rbST treatment (Capuco et al., 1989).
Although, responses of 5'D activity differed among the tissues in the study of Capuco et al. (1989) and Kahl et al. (1995), in both studies, the mammary to liver ratio of 5'D activity was increased for bST-treated cows.Thus, the metabolic priority of the mammary gland could be increased in treated cows either by enhancing general hypo-thyroid status of the cow maintaining euthyroid condition within the mammary tissues (Kahl et al., 1995), or by inducing hyper-thyroid condition in the mammary gland without altering the thyroid status of peripheral tissues or the concentrations of thyroid hormones in the circulation (Capuco et al., 1989).So, the organ-specific responses of 5'D to rbST could be influenced by stage of lactation, season, nutriotional staus, duration, dose and route of rbST administration.
Long-term treatment of lactating dairy cows with rbST influenced thyroid status.In this respect, Kahl et al. (1995) working on primiparous dairy cows received rGRF (12 mg/day) or rbST (29 mg/day) at 118 for 63 days, found that both rGRF and rbST decreased (P<0.001)serum concentrations of T 3 by 10% and the T 3 /T 4 ratio by 20%, while serum concentrations of T 4 were not altered due to rbST treatment.These changes in thyroid status were closely related to an increased concentration of serum ST and milk yield (Binelli et al., 1995).The decreased T 3 /T 4 ratio for cows treated with somatotropic hormones (rGRF and rbST) suggests that 5'D activity was reduced and was associated with the rapid increase in milk yield as a result of rbST treatment.The reduction in concentrations of circulating T 3 reflected a 30% decrease (P<0.001) in hepatic 5'-deiodinase activity in response to rGRF and rbST.Because the magnitude of changes in 5'D activities and in circulating concentrations of iodothyronines did not differ between bGRF and bST, which had similar concentrations of serum ST, all effects of bGRF on thyroid status can be attributed to effects of the endogenous ST or to ensuing effects of increased lactational intensity.These equivalent effects of bGRF and rbST on milk yield and thyroid hormone status suggest that the mechanisms by which bGRF and bST increase milk yield do not differ substantially.
According to Kahl et al. (1995), thyroid status of lactating cows is regulated by thyroidal secretion of T 4 and T 3 and by the enzymatic 5'-deiodination of T 4 to T 3 in extra-thyroidal tissues.Both rGRF and rbST decreased 5'D activity in liver but did not affect 5'D activity in mammary gland.Such observation indicated a decrease in T 3 generation in liver of rbST-treated cows which could be part of a mechanism whereby energy and nutrients are conserved for use by the stimulated mammary gland.Also, decreased extra-thyroidal conversion of T 4 to T 3 appears to serve as an adaptation to many physiological conditions in which overactive metabolism are undesirable.A reduction in circulating T 3 may induce alterations in nutritional flux such as increasing lipolysis in fat depots (Blennemann et al., 1992), which may provide additional nutrients for lactation.The constant generation of T 3 in mammary tissue, in response to rbST treatment, would provide T 3 to synergize with other galactopoietic hormones at the level of mammary gland.In the case of T 4 , Kahl et al. (1995) showed that rbST-treated cows tended to have higher concentrations of T 4 than control.They attributed these increases in T 4 to the decreased extrathyroidal deiodination of T 4 to T 3 .
On the other hand, Kahl et al. (1995) observed that bGRF and rbST treatments did not alter T 3 concentrations in milk.Because generation of T 3 by the mammary gland is a significant source of T 3 in bovine milk, the mammary gland of rbST-treated cows was able to maintain a euthyroid condition despite diminished availability of circulating T 3 .This indicates that secretion of T 3 into milk could not account for the lower serum T 3 in rbST-treated cows.So, the galactopoietic effects of rbST and rbGRF were due to increased metabolic activity of secretory cells rather than to an increase in the number of mammary cells (Binelli et al., 1995).Accordingly, stimulation of milk production by rbST (Binelli et al., 1995) is supported by changes in local thyroid status (Kahl et al., 1995).Taken together, it is suggested that bGRF and rbST increase the hypothyroid status of the lactating cows and maintain euthroid condition in the mammary gland, thus enhancing the metabloic priority of the mammary gland.A study carried on cows that received 29 mg/day rbST, indicated that increased substrate required for enhanced milk fatty acids yield may have been provided through redirection of nutrients to the mammary gland away from adipose tissue and through overall increased metabolism in the mammary gland (Beswick and Kennelly, 2000).

Effect of rbST on reproduction
Many studies have evaluated the effects of rbST on dairy animal reproduction.These effects of rbST on reproduction were related to rbST dose, time of initiation of treatment, time of initiation of breeding and control of other factors such as nutritional status and milk production of cows (Esteban et al., 1994).Phillips (1996) stated that reproductive variables have been focused on production studies including days to open (parturition to concenption interval), days to first service (interval from parturition to first insemination) and services per conception (number of inseminations required to achieve conception).In addition, rbST has effects on the function of the ovarian granulosa cells in vitro (Langhout et al., 1991) and on ovarian function in vivo (De la Sota et al., 1993).Rajamahendran et al. (1989) showed that using rbST (0, 10.3 or 20.6 mg) in Holstein cows from 35 days of lactation until 70 days prior to calving, based on milk progesterone, had no effects on reproductive variables such as days to first ovulation, number of cows with short first cycles, mean cycle length in days, mean peak luteal activity respectively due to rbST treatments.Also, mean days to first observed oestrus, average days open, number of pregnant at 200 days post-calving and incidences of reproductive disorders were not affected by rbST treatments.However, cows receiving 10.3 mg of rbST required fewer services per conception (1.30) than 0 (1.75) or 20.6 mg (1.81) cows.Meanwhile, Nytes et al. (1990) working on dairy cows given 0, 10.3, 20.6 or 30.9 mg bST/day from 14th week after parturition for 30 weeks, observed no noticeable effects on reproductive performance due to rbST.Similar response was found in cows given rbST (0, 100, 200, 300, 400 or 780 mg) commenced at 110 days postpartum and continued until cows dried off (Burchard et al., 1990).Esteban et al. (1994) focused on the reproductive performance of dairy cows treated with rbST (17.2, 51.6 and 86 mg/day) which started at 70 days postpartum and ended at dry-off for 2 consecutive lactations.During the first lactation, multiparous cows treated with rbST decreased (P<0.05)pregnancy rates, increased behavioral anestrus and anestrus confirmed by palpation.

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Such effect was not observed in primiparous cows or in multiparous cows in the second lactation.Meanwhile, rbST-treated primiparous cows had (P<0.05)shorter mean days to first standing estrus in the first lactation.In the second lactation, rbST-treated cows had an increased delayed uterine involution, cystic ovarian condition, behavioral anestrus and anestrus confirmed by palpation.However, no differences was detected in progeny from the treated cows of first lactation as evaluated for rates of growth, morbidity, mortality and for reproductive performance.At the same time, Esteban et al. (1994) reported that because rates of dystocia and retained fetal membranes increased in control and rbSTtreated cows, exposure to rbST was probably not directly related to those changes.The observation that rbST did not increase the risk for a cow developing cystic structures during the early postpartum period of the following lactation agreed with similar finding reported by Cole et al. (1992).Also, Lucy et al. (1991) noticed that rbST may have a direct effect on ovarian tissues.This effect was described as an increase in the number of primary follicles recruited with a subsequent inability of the mature Graafian follicle to show complete dominance as reported by Esteban et al. (1994), who concluded that before definite conclusions are made regarding reproductive performance, repercussions in milk production, energy balance, body condition score and blood metabolites that arise with the use of rbST should be considered.At this point, it has been concluded that rbST treatment at a level of 250 mg at 14-day interval for five successive times pre-puberty is strongly in relation to concentration of GH and IGF-I and in less extent to glucose and urea-N concentration to induce precocious puberty in Friesian heifers (Gabr, 2013).
Many studies have investigated the effects of rbST on ovarian function in dairy cattle.Spicer and Stewart (1996), in an in vitro study to determined whether rbST affect basal estradiol, progesterone and androstenedione produced by granulosa cells of small and large follicles, found that pharmacologic doses of rbST (300 ng/ml) inhibited (P<0.05)estradiol, but physiologic dose of rbST (50 ng/ml), bST had no effect on estradiol production by granulosa cells of small or large follicles.Also, rbST blocked the increase in estradiol production that had been induced by FSH, but it had no effect on progesterone production by granulosa cells or thecal cells of large follicles.Also, Gong et al. (1994) reported similar results, but they found that rbST stimulated basal progesterone and FSH-induced progesterone production by bovine ovarian granulosa cells from large follicles (>10 mm).The rbST, at physiologic doses, could either stimulate or inhibit androstenedione production by thecal cells of large follicles depending on whether thecal cells responded to luteinizing hormone.This finding indicated that rbST might have indirectly affected estradiol production by influencing aromatizable estrogen precursors.In addition to its inhibitory effects on steriod production, rbST also inhibited proliferation of granulosa and thecal cells from large follicles.This effect could be related to the observation that rbST inhibited incorporation of [ 3 H] thymidine, a measure of DNA synthesis, by bovine granulosa cells from large follicles (>10 mm) as repoted by Gong et al. (1993).
The foregoing discussion indicated that the magnitude of reproductive responses of dairy cows to rbST is variable (Phillips, 1996).High doses of rbST treatment (20.6 mg/day) decreased conception rates, increased days open by 28-30%, days to first estrus and twinning rates and there was a trend for increased services per conception (Burton et al., 1990b).However, several studies dealt with the rbST treatments which found no differences in days open, services per conception and days to first estrus at 500 mg/14 day (Weller et al., 1990;Pell et al., 1992) or at 56-700 mg/14 day (Downer et al., 1993).In addition, increases in days open were observed in cows in which rbST treatment was initiated early in lactation, but not when treatment started at mid or late lactation (McGuffey et al., 1991).In a more recent study, Abdel-Rahman et al. (2010), working on Holstein-Friesian cows, found that the days-open showed non-significant differences between subgroups for primiparous cows while there was apparent increase in multiparous cows receiving 250 and 500 mg bST/14 days.They also detected an improvement of conception rate (%) in all treated cows as compared to the control.Furthermore, Chalupa et al. (1996) working on dairy cows injected with rbST (10.3, 20.6 or 41.2 mg bST/d) at d 28 to 35 of lactation, observed that 41.2 mg/day of rbST reduced (P<0.05)pregnancy rate, but did not affect AI services, conception rate and days open.However, rbST at 10.3 or 20.6 mg/day did not adversely affect reproduction.Flores et al. (2007) reported that rbST at 500 mg/14 day in Brahman cows increased (P<0.05) the first-service conception rate during the first 30 days of breeding and pregnancy rates during the first 3 days of breeding.In addition, the success of embryo transfer in cattle can be compromised by low pregnancy rates.The use of rbST in lactating dairy cows increased pregnancy rates following the transfer of frozen-thawed embryos (Moreira et al., 2002), and this effect may be mediated directly by rbST or indirectly by IGF-I (de la Sota et al., 1993).
The observed decreases in reproductive performance of dairy cattle treated with rbST may be attributed more to the increases in milk yield and short-term negative energy balance than to direct effects of rbST (Weller et al., 1990).According to Phillips (1996), days open was more related to level of milk production than rbST.In addition, treatment with rbST increases milk energy output before there is a concomitant increase in feed intake and therefore, following initiation of rbST treatment, treated cows tend to be in more negative energy balance which is known to reduce reproductive performance.In the early post-partum period of dairy cows, the duration and intensity of negative energy balance, the level of body condition score loss and the milk yield are strongly associated with the timing of the first ovulation.In this respect, pre-partum administration of rbST (500 mg) in late pregnant Holstein heifers did not affect the milk production, plasma β-hydroxybutyrate and nonesterified fatty acids concentrations, the time of the first post-partum ovulation and the proportion of cows ovulating the first post-partum follicular wave showes that pre-partum rbST treatment in dairy heifers with high body condition score seems not to have any effect on markers of energy balance, milk production or development of the first follicular wave in the early post-partum period (Acosta et al., 2013).

Effect of environmental conditions on animal response to rbST
Several studies have documented the negative effects of hot or cold conditions on milk production.Responses of milk yield to rbST treatments during heat stress appear to be smaller than under more moderate conditions (Staples et al., 1988).
Working on Holstein lactating cows at 46-106 days postpartum, Zoa-Mboe et al. ( 1989) evaluated the effects of rbST injection (20.6 mg/d) and environment (shade and no shade systems) on milk production and physiological functions of dairy cows.The ambient temperature ranged between 21.2-32.3°Cand humidity between 50-90%.The rectal temperature (RT) and respiration rate (RR) of cows were higher (P<0.05) in no shade than in shade.The rbST-treated cows had slightly higher (P<0.05)RT and RR.This increase in RT and RR might have resulted from increased metabolic heat production, and this would increase slightly the need of rbST-treated cows to dissipate their body heat.However, comparable increases in RT and RR of rbST-treated cows were not observed under more moderate environmental conditions during full lactation (Soderholm et al., 1988).The rbST supplementation with 500 mg/14 day in crossbred Holstein cattle under hot and humid condition affected body acid-base homeostasis (Thammacharoen et al., 2011).
Zoa-Mboe et al. ( 1989) also observed that yields of milk and 3.5% FCM and DMI of cows in no shade were 9.5 and 16% less (P<0.05)than for cows in shade.Much of the effect of heat stress on milk production was associated with reduced DMI.The rbST injection increased (P<0.05)3.5% FCM and milk component yields, while milk yield was increased insignificantly by 4.5% (1.1 kg/d).DMI and gross efficiency (FCM/DMI) were unaffected by rbST treatment.The two environmental systems did not affect plasma metabolites and hormones (glucose, NEFA, insulin, prolactin, bST, T 3 and T 4 ).Also, rbST treatment had no significant effect on plasma constituents, except rbST-injected cows which had greater (P<0.001)concentrations of plasma bST.It seems apparent that cows in shade or no shade systems were impacted by heat stress, and this might explain why responses of cows to rbST were not different under the two environmental systems (Zoa-Mboe et al., 1989).
On the other hand, Becker et al. (1990) observed that short-term injection of rbST in cows kept under cold stress of ambient temperature ranging from -5 to 5°C increased their milk yield.Also, milk production was increased for rbST-treated Holstein and Jersey dairy cows exposed to hot conditions in which ambient temperature ranged 22-35°C and humidity 30 to 100% (West et al., 1990;Johnson et al., 1991).However, Zoa-Mboe et al. (1989) reported that increased production responses to rbST in heat-stressed dairy cows were less than in cows injected with rbST under more moderate conditions.Thus, just as milk yield is reduced in nontreated cows maintained under heat stress conditions, milk yield response to rbST is also reduced (Philips, 1996).Reasons may be related to need of dairy cows to maintain their body core temperature by decreasing heat production and increasing insensible heat loss.The rbST treatment (31 mg) increased milk production similarly during the thermoneutrality and heat-stress periods, ∼8.3% over the control and this increase occurred together with the elevation in core body temperature (Settivari et al., 2007).It has been suggested that exogenous rbST is efficacious in increasing milk yield without adverse effects on lactating crossbred Holstein cows in a tropical environment (Chaiyabutr et al., 2011).Under tropical conditions, it has been demonstrated that the rbST exerts its galactopoietic action, in part, through increases in total body water, empty body water and extracellular water in association with an increase in mammary blood flow, which partitions the distribution of nutrients to the mammary gland for milk synthesis in crossbred cattle (Chaiyabutr et al., 2007).Therefore, strategies to overcome heat stress of moderate and high producing dairy cows should permit greater benefits to be realized from use of rbST in tropical and subtropical environmental conditions (Zoa-Mboe et al., 1989).

Effects of rbST on animal health and immune system
Effects of rbST treatment on the health of dairy cows have been reviewed (Phillips, 1996).As observed by Soderholm et al. (1988), adminstration of rbST to cows did not influence their body temperature or respiration rate, but heart rate increased by 5-15%.Although, Burton et al. (1990b) observed no significant increase in leg or hoof problems in rbST-treated cows, Cole et al. (1992) and Zhao et al. (1992) reported increased incidence of of lameness in rbST-treated cows.Meanwhile, some metabolic diseases such as milk fever or ketosis did not affect rbST treatment (Bauman, 1992).Also, Nytes et al. (1990) observed no adverse affect on health or incidence of disease due to rbST.Chalupa et al. (1996) showed that the infertility was about 3 times greater for 41.2 mg, Soliman and EL-Barody 9 rbST treated-cows than for untreated, but there was no indication (P>0.10) of increases in pregnancy failure incidence of ketosis, abomasal displacement, feet and leg problems or clinical mastitis in 10.3 or 20.6 mg bSTtreated cows.However, 41.2 mg bST-treated cows tended to have more feet and leg problems and required antibiotic for mastitis and have higher somatic cell counts (SCCs) in milk.
According to Phillips (1996), the effects of rbST on udder health and the incidence of mastitis are important.So, many studies examined the number of clinical cases of mastitis that coincided with the treatment of rbST.Also, SCCs in milk have been evaluated as an indirect index of subclinical mastitis.However, the effect of rbST on SCC and mastitis is variable.Some studies indicated that SCC increased in rbST-treated cows (Oldenbroek and Garssen, 1990), but others found no differences in SCC in treated and non-treated cows (Zinn et al., 1993).In case of mastitis, no significant effect on incidence of mastitis and health problems was seen for cows given rbST at doses from 100 to 780 mg.However, increased incidence of mastitis appears to be more related to random effects than specifically to rbST (Pell et al., 1992).Thus, White et al. (1994) found no association between rbST treatment and the incidence or duration of clinical mastitis.They concluded that under normal conditions, there is a positive relationship between the incidence of mastitis and peak and total milk yield and that treatment with rbST did not alter this relationship.So, cows that produce more milk normally have a greater tendency to develop mastitis and this relationship exists regardless of the use of rbST (White et al., 1994).Accordingly, the incidence of mastitis in rbST-treated cows is due more to the increased milk yield than to any direct effects of rbST (Phillips, 1996).
Immune status of lactating cows given rbST (10.3 and 20.6 mg/day) for 38 weeks was studied by Burton et al. (1990a) who found that rbST treatment at 10.3 mg/day increased IgG and IgG2 by 12.4 and 18.4%, respectively than the control.At dosages that are efficacious for lactation, rbST is not detrimental to humeral immune or cell-mediated immune responses as determined by serum concentrations of IgG, IgG1, IgG2 and IgGA.Additionally, in primiparous and multiparous cows given rbST doses at 250 and 500 mg/14 days, the leucogram showed a non significant leucocytosis accompanied with neutrophilia and lymphocytosis (Abdel-Rahman et al., 2010).

EFFECT OF rbST ON LACTATING SHEEP AND GOATS
The galactopoietic effects of bST are well established in sheep (Stelwagen et al., 1993) and dairy goats (Knight, 1992).However, a few studies have investigated the effect of rbST on milk production in lactating dairy ewes and goats.The milk yield responses to rbST treatment in goats and sheep are more variable than that in cows (Davis et al., 1999).The rbST has been shown to be active in goats (Puchala et al., 2001).
In the case of sheep, Fernandez et al. (1995) used 74 lactating dairy ewes injected with rbST at 0, 80, 160 or 240 mg every 14 days from 3 to 8 weeks of lactation (part 1) and 0, 80 or 160 mg every 14 days from 11 to 23 weeks of lactation (part 2).They showed that rbST treatment increased milk yield (P<0.01) at all treatments over the control.The largest increase in milk yield was at 160 mg of bST by which milk yields increased by 34.1 and 53.2% and 6% FCM by 36.9 and 51.8% for parts 1 and 2, respectively.The rbST increased milk fat during part 1, but decreased milk fat during part 2. Protein content of milk was decreased while yield of milk constituents were increased.The rbST did not affect milk lactose during part 1, but increased milk lactose in part 2. Milk yield constituents were increased due to rbST treatments.Fernandez et al. (1995) also showed that neither mastitis incidence nor milk SCC was affected by bST treatment.Therefore, they concluded that bST is efficacious in increasing both actual milk yield and 6% FCM over the dose range of 80 to 240 mg/14 days without adverse effects on lactating ewes.Bassett et al. (1998), working on lactating sheep, confirmed the galactopoietic effects of rbST (0.1 mg/kg/day) and suggested that the mechanism of this action is not via increased hepatic growth hormone receptor number or gene expression.They added that the increase in hepatic but not mammary IGF-I mRNA with rbST treatment suggests an endocrine action of IGF-I on milk synthesis.In a recent study, Requena et al. (2010) determined the effect of administration of rbST (40, 80 and 120 mg/14 day) in lactating ewes.They found that the treatment 120 mg of bST yielded 39% more actual milk and 44 more 6% FCM; and increased actual milk fat percentage, but did not affect the other milk components or somatic cell count, concluding that rbST increased potential milk yield throughout lactation and actual milk yield only after weaning in dairy ewes, however it was not useful for reducing the milk yield loss that occurred at weaning.With rbST dose titration and treatment interval in lactating dairy ewes, Fernandez et al. (2001) concluded that the period between successive injections should be shorter, the dose employed lower; however, a 14-day period seemed to correspond correctly to the dosages and hormone formulation tested.Even though exogenous administration of rbST effectively increases milk yield, more permanent and profitable results can be achieved by enhancing technical practices, focusing on better genetic goals for dairy sheep, and taking care of udder health (Pulina et al., 2007).On the other hand, injection with 100 mg rbST/biweekly increased the average daily gain and improved the physiological status of growing post weaning growing Rahmani lambs (Nour El-Din et al., 2009).In addition, administration of 80 mg rbST/lamb, at 14-days interval starting at 2 month of age for both male and female lambs produced from crossbreed ewes (½ Finnish Landrace x ½ Rahmani) previously treated with 160 mg rbST/ewe, improved growth performance and some puberty characteristics in male lambs and slightly improved age at puberty in ewe lambs (El-Gohary et al., 2011).
In the case of goats, Davis et al. (1999) using 14 multiparous Angora does injected with rbST (100 µg/kg BW/d), showed that body weight and dry matter intake of does were not affected by rbST treatment.Kids of rbSTtreated does had higher (P<0.05)average daily gain (ADG) by 32% than the kids of control, suggesting that kid ADG is probably a good indicator of actual milk production.However, milk yield was insignificantly increased by 15% for rbST-treated does than control.These increases in milk yield and ADG of the kids of rbST-treated does without change in DMI or BW of does are consistent with similar responses in milk yield by lactating cows treated with rbST without corresponding increase in DMI (Downer et al., 1993;Bareille et al., 1997).No carryover effect of bST on milk production was observed in goats (Knight, 1992;Davis et al., 1999).The lack of change in milk composition (fat, protein, lactose and total solids) in rbST-reated goats observed by Davis et al. (1999) is consistent with previous report on goats (Nielsen, 1988) and cattle (Dahl et al., 1993).Furthermore, in rbST-treated goats (Davis et al., 1999), concentrations of plasma NEFA, total protein, glucose, insulin, urea and amino acids were not affected by rbST treatment.Such observation in goats disagree with study of Sechen et al. (1989a), who reported that treatment of cows with bST increased milk yield and plasma concentrations of NEFA, but that there were no changes in plasma glucose, insulin and glucagon.In the study of Sechen et al. (1989a), the increase in milk energy secretion made the cows to be in negative energy balance, which resulted in a chronic elevation of circulating NEFA.Changes in plasma concentrations and increased oxidation of NEFA have been reported in dairy cows that were in negative energy balance during bST treatment (Sechen et al., 1989b).The unchanged concentrations of plasma amino acids agree with similar trend observed by Davis et al. (1995).
Plasma concentrations of T 4 and cortisol were decreased, while plasma ST and IGF-I were elevated (P<0.05)chronically in bST-treated goats (Davis et al., 1999).Similar trend of plasma ST and IGF-I were reported by Davis et al. (1999) in goats injected daily with bST (100 µg/kg BW/day).In this respect, Prosser et al. (1990) reported increase in milk yield of goats which coincided with increased plasma concentrations of IGF-I.There is a complex interaction between rbST administration and thyroid hormone status in Angora goats as reported by Puchala et al. (2001) who showed that in the case of hypothyroid, rbST increased plasma concentrations of T 3 and T 4 , however, in the cases of euthyroid or hyperthyroid, rbST had no effect on thyroid hormones.
These findings indicate that rbST maintained the normal thyroid status.A study on Damascus lactating goats in their third to fourth lactation season and at 30-40 days postpartum were subcutaneously and biweekly received an injection for 8 weeks with low (50 mg/doe) or high (100 mg/doe) doses of rbST, Sallam et al. (2005) found that the DMI or BW of does were not affected significantly by rbST treatment, while ADG of kids suckling rbSTtreated does was higher by 11.0 and 10.5% for low and high doses of rbST, respectively than for kids of control does.They also found that administration with rbST resulted in a significant (P<0.05)total milk yield by 24.3 and 22.5% for 50 or 100 mg rbST, respectively when compared with the control.There were insignificant increase in the levels of total solids, milk protein and fat, while lactose was significantly (P<0.05)increased due to rbST exposure.Sallam et al. (2005) also showed that ash, hematological parameters, plasma protein and the activities of plasma AST, ALT, glutathione S-transferase, alkaline phosphatase, acid phosphatase and the levels of thiobarbutric acid-reactive substances, creatinine and cholesterol were not affected by the rbST treatments, while administration of rbST significantly (P<0.05)increased plasma glucose levels and decreased those of urea and total bilirubin.Injection of rbST at 20, 40 and 60 mg/14 days to West African Dwarf goats increased their milk yield by 50.4,68.0 and 71.2%, respectively, suggesting that rbST administration to goats after peak of lactation can enhance milk yield, galactopoiesis and persistency of lactation, indicating higher milk yield in extended lactation (James et al., 2010).Recently, the treatment of lactating goats with rbST rapidly increased milk yield after the onset of treatment according to Qudus et al. (2013).They reported that, injection with 50 and 100 mg/week of rbST for 8 weeks in lactating goats increased milk production by 28 and 29%, respectively, accompanied by no significant effect on milk composition and without any adverse effect on health of goats.Similar results were previously observed by Chadio (2009) in lactating goats.

CONCLUSION
The rbST has a galactopoietic effect which improves milk production in dairy animals without adverse effect on milk quality or animal health and reproduction.The mechanistic aspects that involved the positive effects of rbST could be included which increased the metabolic activity of mammary cells or slow their involution, without affecting mammary cell numbers or mammary remodeling, thereby allowing more secretory cells to persist over time and contribute to increasing milk synthesis and yield.Furthermore, rbST increase the hypothyroid status of the lactating cows and maintain euthroid condition in the mammary gland, thus enhancing the metabolic priority of the mammary gland.With rbST treatment, the increased substrate required for enhanced milk fatty acids yield Soliman and EL-Barody 11 may have been provided through redirection of nutrients to the mammary gland away from adipose tissue and through overall increased metabolism in the mammary gland.As well, rbST increases the capture of dietary nutrients in milk by decreasing the relative proportion of consumed nutrients needed for maintenance and by partitioning nutrients into milk rather than into body reserves, therefore, the main effect of rbST was decreased body fat reflecting the partitioning of calories by rbST to milk at the expense of fat deposition.