Effect of whole-milk allowance on liveweight gain and growth of parenchyma and fat pads in the mammary glands of dairy heifers at weaning.

The rates of development of 2 tissues in mammary glands, parenchyma (PAR) and the mammary fat pad (MFP), in response to nutrition in early life might have a major bearing on lifetime milk production. Historical studies reported that feeding greater amounts of dietary nutrients from postweaning to puberty increased growth rates of heifers and stimulated the growth of MFP at the expense of PAR, which might suggest compromised mammary development and future milk production. The current study sought to determine if a higher volume of whole milk (8 vs. 4 L/d) offered to calves would increase rates of growth and development of PAR in mammary glands at weaning (1 to 12 wk). To measure these tissues, we developed 2 simple methods to assess the size of PAR and MFP at the time of screening using ultrasound. We report that calves offered 8 L/d of whole milk had greater rates of growth until weaning (0.86 ± 0.06 vs. 0.81 ± 0.09 kg/d), compared with calves offered 4 L/d. Ultrasonography showed that despite the faster rates of growth in calves offered 8 L/d of milk/d, the ratio of PAR:MFP depth was 40% less at weaning in the front glands (34%) compared with calves offered 4 L of milk/d. Rear glands were less impaired. The ultrasound methods developed here might be useful to monitor the development of mammary glands in response to different nutritional regimens during the preweaning period.

Ultrasonography to investigate the effect of supplementing whole milk with complex carbohydrates and specific amino acids on curd retention in the abomasum of dairy calves.

AIM: To determine whether the retention time of curd in the abomasum of calves was influenced by supplementing milk with a plant-derived carbohydrate and amino acid supplement, evaluated non-invasively using ultrasonography. METHODS: Female dairy calves aged between 2-6 days of age were sourced from a commercial farm in March 2013. All calves were fed whole milk until weaning (4 L per day); 21 calves were supplemented with a probiotic until 18 days of age, and thereafter with a plant-derived complex carbohydrate and amino acid supplement until weaning, and 22 calves were just fed whole milk. Treatment groups were balanced for age, weight and breed. At 9-14, 24-29 and 52-57 days of age, the abomasum of each calf was examined using ultrasonography immediately before and after feeding, 1 and 2 hours after feeding, and then at 30 minute intervals until curd was no longer visible in the abomasum. Abomasal volume and curd size were recorded to assess retention time of curd in the abomasum. RESULTS: At 9-14 days of age, mean retention time of curd in the abomasum was similar (4.6 hours) in both groups. At 24-29 days of age, when the supplemented calves had been receiving the supplement for approximately 10 days, mean curd retention time was longer by 1.4 (SE 0.28) hours in supplemented compared with unsupplemented calves (p<0.001). At 52-57 days of age, mean retention time was longer by 0.7 (SE 0.34) hours compared to unsupplemented calves (p=0.05). CONCLUSION: Using ultrasonography, changes in abomasal content could be followed non-invasively over time and it was demonstrated that the plant-derived complex carbohydrate supplement increased the curd retention time in the abomasum. We speculate that the increased retention time enables an increased availability of nutrients following a more complete digestion of milk, thereby improving animal performance.

Lifelong exercise and locally produced insulin-like growth factor-1 (IGF-1) have a modest influence on reducing age-related muscle wasting in mice.

The age-related loss of skeletal muscle mass and function is termed sarcopenia and has been attributed to a decline in concentrations of insulin-like growth factor-1 (IGF-1). We hypothesized that constitutively expressed IGF-1 within skeletal muscles with or without exercise would prevent sarcopenia. Male transgenic mice that overexpress IGF-1 Ea in skeletal muscles were compared with wild-type littermates. Four-month-old mice were assigned to be sedentary, or had access to free-running wheels, until 18 or 28 months of age. In wild-type mice, the mass of the quadriceps muscles was reduced at 28 months and exercise prevented such loss, without affecting the diameter of myofibers. Conversely, increased IGF-1 alone was ineffective, whereas the combination of exercise and IGF-1 was additive in maintaining the diameter of myofibers in the quadriceps muscles. For other muscles, the combination of IGF-1 and exercise was variable and either increased or decreased the mass at 18 months of age, but was ineffective thereafter. Despite an increase in the diameter of myofibers, grip strength was not improved. In conclusion, our data show that exercise and IGF-1 have a modest effect on reducing aged-related wasting of skeletal muscle, but that there is no improvement in muscle function when assessed by grip strength.

Intracerebroventricular melanin-concentrating hormone stimulates food intake in sheep.

Melanin-concentrating hormone (MCH) stimulates feeding when injected intracerebroventricularly (ICV) in rats. At present it is not clear whether the function of MCH is similar in ruminants, which are species with a continuous delivery of nutrients. Therefore the current investigation sought to determine the role of MCH in sheep. In the first experiment, six, castrate male sheep were satiated and received one of four treatments [saline, 0.1, or 1.0 nmol/kg MCH, and NPY (0.1 nmol/kg)] injected ICV over 30s, then infused ICV for 6 h ( approximately 500 microl/h). Food intake was measured for 2 h before and at 2, 4, 6, 8, 12 and 24 h. In this experiment, feed intake was increased (P

Melanocortin-4 receptor in sheep: a potential site for therapeutic intervention in disease models.

Reduced appetite combined with increased metabolic rate and decreased lean body mass is a major consequence of disease and other stressors. Studies in rodent species suggest that an understanding of appetite regulation may provide methodologies for intervention to prevent the deterioration of body mass such as observed with cancer or infectious diseases. For example, melanocortin-4 receptor (MC4-R) antagonists have shown a remarkable ability to reverse or prevent cachexia in rodents with sarcoma or treated with endotoxin. Studies in sheep have indicated that a number of peptide neurotransmitters may have a role in regulating appetite in this species. For example, agouti related protein mRNA and protein levels are dramatically altered with fasting in sheep. Moreover, agouti related protein, neuropeptide Y, melanin concentrating hormone and orexin are potent stimuli to increase feed intake in sheep. Recent studies have indicated that one of these neurotransmitters, NPY, can work in principal to improve appetite in endotoxin-treated sheep. Current studies are examining the role that MC4-R antagonists may have in the prevention or correction of body mass wasting diseases as well as practical applications in animal production.

Undernutrition regulates the expression of a novel splice variant of myostatin and insulin-like growth factor 1 in ovine skeletal muscle.

Undernutrition suppresses the growth of skeletal muscles and alters the expression of insulin-like growth factor 1 (IGF1), a key mitogen, and myostatin, a potent inhibitor of myogenesis. These changes can explain, at least in part, the reduced growth of skeletal muscles in underfed lambs. We have recently identified a myostatin splice variant (MSV) that binds to and antagonizes the canonical signaling of myostatin. In the present study, we hypothesized that the expression of MSV would be reduced in conjunction with myostatin and IGF1 in response to underfeeding in skeletal muscles of sheep. Young growing ewes were fed either ad libitum or an energy-restricted diet (30% of maintenance requirements) for 28 d. This regime of underfeeding resulted in a 24% reduction in body mass (P < 0.001) and a 36% reduction in the mass of the semitendinosus muscles relative to controls (P < 0.001) by day 28. The concentrations of MSV and IGF1 messenger RNA (mRNA) were reduced (both P < 0.001), but myostatin mRNA was not altered in semitendinosus muscles. Unlike the reduced expression of mRNA, the abundance of MSV protein was increased (P < 0.05) and there was no change in the abundance of myostatin protein. Our results suggest that undernutrition for 28 d decreases the signaling of myostatin by increasing the abundance of MSV protein. Although this action may reduce the growth inhibitory activity of myostatin, it cannot prevent the loss of growth of skeletal muscles during undernutrition.

GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding.

After a meal, somatotropes are temporarily refractory to growth hormone-releasing hormone (GHRH), the principal hormone that stimulates secretion of growth hormone (GH). Refractoriness is particularly evident when free access to feed is restricted to a 2-h period each day. GH-releasing peptide-6 (GHRP-6), a synthetic peptide, also stimulates secretion of GH from somatotropes. Because GHRH and GHRP-6 act via different receptors, we hypothesized that GHRP-6 would increase GHRH-induced secretion of GH after feeding. Initially, we determined that intravenous injection of GHRP-6 at 1, 3 and 10 microg/kg body weight (BW) stimulated secretion of GH in a dose-dependent manner. Next, we determined that GHRP-6- and GHRH-induced secretion of GH was lower 1 h after feeding (22.5 and 20 ng/ml respectively) than 1 h before feeding (53.5 and 64.5 ng/ml respectively; pooleds.e.m.=8.5). However, a combination of GHRP-6 at 3 microg/kg BW and GHRH at 0.2 microg/kg BW synergistically induced an equal and massive release of GH before and after feeding that was fivefold greater than GHRH-induced release of GH after feeding. Furthermore, the combination of GHRP-6 and GHRH synergistically increased release of GH from somatotropes cultured in vitro. However, it was not clear if GHRP-6 acted only on somatotropes or also acted at the hypothalamus. Therefore, we wanted to determine if GHRP-6 stimulated secretion of GHRH or inhibited secretion of somatostatin, or both. GHRP-6 stimulated secretion of GHRH from bovine hypothalamic slices, but did not alter secretion of somatostatin. We conclude that GHRP-6 acts at the hypothalamus to stimulate secretion of GHRH, and at somatotropes to restore and enhance the responsiveness of somatotropes to GHRH.

Effects of season, protein and nutritional state on glucose tolerance during an annual cycle of growth in young red deer stags.

Two hypotheses were tested in gonad-intact, young (aged 6-18 months), growing red deer stags during an annual growth cycle. First, that glucose clearance rate is faster during summer than during winter. Secondly, that increased dietary protein availability will enhance winter growth. Stags were randomly assigned into one of two groups: group 1 (n = 5) had 16% while group 2 (n = 6) had 48% of dietary protein naturally protected against fermentative degradation in the rumen. Total crude protein and energy remained similar for each diet (12 and 14% respectively for protein and 11 MJ metabolisable energy/kg dry matter). Stags were kept indoors in individual pens for 12 months and given monthly intravenous glucose tolerance tests (IVGTT), at a dose of 200 mg/kg, in the fed and fasted (48 h) states to determine both growth and steady-state tissue requirements. Protein level had no effect on food intake, weight gain, insulin kinetics, or glucose clearance rate. In the fed state, insulin peak (highest level' after IVGTT) increased (P < 0.01) from October (139 pmol/l) to December (247 pmol/l) (S.E.D. = 42) and remained elevated during the summer, before declining (P < 0.01) from February (223 pmol/l) to April (130 pmol/l) (S.E.D. = 25). Glucose clearance rate was faster (P < 0.05) in December (1.69 litres/min) than June (0.61 litres/min) in the fed state (S.E.D. = 0.30), and decreased (P < 0.05) from February (1.75 litres/min) to April (0.92 litres/min) (S.E.D. = 0.39). During fasting, the pattern of glucose clearance was similar to that observed in the fed state, but the amplitude was lower, while the pattern for insulin peak was similar to that of the fed state. We concluded first, that additional protected protein does not benefit growth during winter. Secondly, we concluded from the fasted, steady-state data that stags are insulin resistant during summer. Thirdly, despite insulin resistance, data on the fed state demonstrated that stags have higher tissue energy requirements during summer growth.

Estradiol/progesterone implants increase food intake, reduce hyperglycemia and increase insulin resistance in endotoxic steers.

High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature and concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of GH and IGF-I are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes in concentrations of GH and IGF-I, (3) reduce inappetence and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), and (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2x2 factorial arrangement of treatments as follows (n=5 per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 microg/kg body weight (BW), i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (day 0) and serial blood samples (15 min) were collected on day 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0. 05) at 6 and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased 1 h after injection of LPS, then were reduced for 2 h. Appetite was greater (P<0.05) in S/E- (2.1% BW) compared with C/E-treated steers (1.1% BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. LPS did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid-treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via anti-inflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.

Neuropeptide Y restores appetite and alters concentrations of GH after central administration to endotoxic sheep.

The objective of this study was to determine whether neuropeptide Y (NPY) and recombinant human interleukin-1 receptor antagonist (IL-1ra) would: first, increase food intake; secondly, decrease concentrations of GH; thirdly, reduce GHRH-induced release of GH; and fourthly, reduce changes to concentrations of IGF-I in plasma during experimental endotoxemia in sheep. Six treatments were given to six castrated male sheep in a 6x6 Latin square treatment order. Osmotic mini-pumps were implanted at 0 h and a jugular vein was cannulated. Each sheep was continuously infused with saline (0.9%) or lipopolysaccharide (LPS) (20 micrograms/kg per 24 h, s.c.) at 10 microliters/h for 72 h via the osmotic mini-pumps. Blood samples (3 ml) were collected at 15-min intervals from 24 to 33 h. At 26 h, one of three treatments (artificial cerebrospinal fluid, NPY or IL-1ra) was injected i.c.v. within 30 s (0.3 microgram/kg), then infused i.c.v. from 26 to 33 h (600 microliters/h) at 0.3 microgram/kg per h. GHRH was injected i.v. (0.075 microgram/kg) at 32 h after which blood samples were collected at 5, 10, 15, 30, 45 and 60 min. Feed intake was reduced up to 50% for 48 h in LPS-treated compared with non-LPS-treated sheep. NPY restored feed intake in LPS-treated sheep and induced hyperphagia in non-LPS-treated sheep from 24 to 48 h. In contrast, IL-1ra did not affect appetite. Injection of NPY increased concentrations of GH from 26 to 27 h, while IL-1ra had no effect. Infusion of NPY suppressed GHRH-induced release of GH. However, no treatment altered pulse secretion parameters of GH. Concentrations of IGF-I were 20% higher at 72 h in LPS-treated sheep given NPY than in sheep treated with LPS alone, and this may reflect increased appetite from 24 to 48 h. We concluded that reduced appetite during endotoxemia is due to down-regulation of an NPY-mediated mechanism. Furthermore, NPY stimulates release of GH in healthy sheep, does not reduce pulse secretion parameters of GH, but does suppress GHRH-induced release of GH in endotoxic sheep. Therefore, NPY may be an important neurotransmitter linking appetite with regulation of GH during endotoxemic and healthy states in sheep.

Adverse effects experienced by patients taking timolol.

Adverse effects involving one or more organ systems occurred in 38 of 165 patients with various types of glaucoma when timolol was added to their glaucoma therapy. It was necessary to discontinue timolol because of these side effects in 15 (9%) of the patients. Double-masked studies will be necessary to clarify the relationship of these adverse effects to the use of timolol.

Embryo development and placentome formation during early pregnancy in red deer.

Early embryo development and placentome formation were assessed in red deer between Days 27 and 55 of gestation. Uteri were collected from 12 pregnant hinds in which mating was observed following a synchronized oestrus, and the tissues retained for measurements and histological processing for light microscopy. Twelve embryos were recovered with mean embryo weights increasing from 0.02+/-0.01 g at Day 27 to 7.56+/-1.39 g at Day 55 of gestation. Similarly, crown-rump lengths increased from 5.7+/-0.7 mm to 55.3+/-5.9 mm over this period. The trophoblast had extended throughout both uterine horns and gastrulation was completed by Day 27. Limb buds were apparent by Day 34, and by Day 48 the phalanges had separated into hooves and dew claws. Plaques were evident on the trophoblast at Day 34 and, by Day 41, placentomes had formed adjacent to the embryo. These placentomes grew in size as pregnancy advanced; by Day 55 most caruncles had formed placentomes. It is therefore confirmed that placentome formation occurs at about the sixth week of gestation. These results indicate that embryo growth and placentome formation in red deer are generally typical of that observed in other ruminants.

Thyrotropin-releasing hormone mediates serotonin-induced secretion of GH in cattle.

Serotonin stimulates secretion of growth hormone (GH) in cattle, but the mechanism is unknown. In rats, thyrotropin-releasing hormone (TRH) mediates serotonin-induced secretion of GH. We hypothesized that the same is true in cattle. Cattle were fed for 2h daily to synchronize secretion of GH, such that concentrations of GH were high before and low after feeding. Our first objective was to determine whether or not feeding suppresses serotonin receptor agonist (quipazine) induced secretion of GH. Holstein steers were injected with quipazine (0.2 mg/kg BW) either 1 h before or 1 h after feeding. Quipazine-induced secretion of GH which did not differ in magnitude before and after feeding. If TRH mediates serotonin-induced secretion of GH, then magnitude of TRH-induced secretion of GH should not be different before and after feeding (our second objective). Sixteen meal-fed Holstein steers were injected with 0.3 microg TRH/kg BW either 1 h before or 1 h after feeding. Indeed, magnitude of TRH-induced secretion of GH before and after feeding was not different. Our third objective was to inhibit endogenous TRH with 3,5,3'-triiodothyronine (T(3)) and examine basal, GH-releasing hormone (GHRH)-, TRH- and quipazine-induced secretion of GH. Sixteen Holstein steers were injected daily with either T(3) (3 or 6 microg/kg BW) or vehicle for 20 days and then challenged sequentially with vehicle or GHRH, TRH, or quipazine. T(3) did not affect basal, GHRH- or TRH-induced secretion of GH, but reduced basal secretion of thyroxine. T(3) reduced but did not completely block quipazine-induced secretion of GH. In conclusion, TRH mediates, in part, serotonin-induced secretion of GH in cattle.

Endocrine modulation of physiological responses to catabolic disease.

Disease or endotoxemia alters the plasma concentrations of anabolic hormones, particularly growth hormone (GH) and insulin-like growth-factor I (IGF-I). In general, these hormones are inhibited during the catabolic disease state. A hypothesis has evolved that anabolic hormones might be useful in patients' recovery under these and other catabolic circumstances. The treatment of cattle with GH has provided significant improvement in the physiological response of the animals to the subsequent injection of bacterial lypopolysaccharide (LPS), perhaps via inhibition of tumor necrisis factor (TNF) release. However, this improved response to disease was not observed with animals treated with GH and infected with one of two parasitic organisms, Sarcocystis cruzi or Eimeria bovis. Recent attempts with other anabolic hormones, estradiol and progesterone, have proven remarkably effective in improving the adaptive physiological responses of calves to either E. bovis infection or to the injection of LPS. All animals displayed signs of infection, but the intensity and duration of symptoms were reduced. Although a mechanism is not yet known, there were no effects on TNF; cortisol; the percentages of lymphocytes expressing CD2, 4, or 8 antigens; or the production of antibodies.

Stimulation of dopamine D1 receptors increases activity of periventricular somatostatin neurons and suppress concentrations of growth hormone.

The selective dopamine D1 receptor agonist, SKF38393, stimulates release of somatostatin (SS) from perifused bovine hypothalamic slices. Therefore, we hypothesized that SKF38393 activates SS neurons, which, via release of SS, would suppress concentrations of growth hormone (GH) in serum in calves. Our objectives were to determine whether SKF38393: (1) increases the percent of immunoreactive c-Fos protein and Fos-related antigens (Fos/FRA) detected in somatostatin neurons in periventricular (PeVN) and arcuate (ARC) hypothalamic nuclei; (2) reduces concentrations of GH in serum; (3) suppresses growth hormone-releasing hormone (GHRH)-induced release of GH. Meal-fed steers were used to perform these objectives because a synchronous pulse of GH occurs 1-2 hr before feeding in steers allowed access to feed for 2 hr each day. In Experiment 1, two groups of four Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW). Steers were injected i.v. with a lethal dose of sodium pentobarbital 100 min later and their brains were fixed with 4% paraformaldehyde. Dual-label immunohistochemistry was performed on 40 microns free-floating sections using antiserum to SS and to Fos/FRA on sections containing PeVN and ARC nuclei. More SS neurons were detected in the PeVN than in the ARC. The percent of SS neurons with immunoreactive Fos/FRA present was 2.9-fold higher in SKF38393-treated compared with vehicle-injected steers in the PeVN, but was unchanged in the ARC. In Experiment 2, eight Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW) 140 min before meal-feeding. In contrast to controls, concentrations of GH in serum of SKF38393-treated steers did not increase during 140 min before meal-feeding. In Experiment 3, eight Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW), then 100 min later, each steer was injected i.v. with [Leu27,Hse45] bGHRH1-45 lactone (0.2 micrograms/kg BW). Bovine GHRH stimulated release GH into serum in both groups, but concentrations of GH were lower in SKF38393-treated steers. These results show that stimulation of D1 receptors selectively increases activity of SS neurons in the PeVN, and this increased activity is associated with suppressed basal- and GHRH-induced release of GH in serum of meal-fed steers.

Feeding-induced increases in insulin do not suppress secretion of growth hormone.

Secretion of growth hormone (GH) is reduced for several hours after feeding when access to feed is restricted to a 2-hr period each day. We hypothesized that increased secretion of insulin after feeding inhibits release of GH from the anterior pituitary gland. Our objectives were to determine whether: 1) alloxan prevents concentrations of insulin from increasing after feeding steers; 2) concentrations of GH remain high after feeding alloxan-treated steers; and 3) GH-releasing hormone (GHRH) stimulates greater release of GH in alloxan-treated, than in control, steers after feeding. Steers were injected iv with either saline (control) or with alloxan (110 mg/kg) (n = 4 per group). Concentrations of insulin were not different (P = 0.61) between control and alloxan-treated steers before feeding (87.5 +/- 33.6 pmol/l). However, alloxan prevented insulin from increasing (P < 0.001) after feeding (131.8 pmol/1) compared with control steers (442.0 pmol/l) (pooled SEM = 47.5). Overall, GH was higher (P < 0.05) in alloxan-treated (6.4 ng/ml) than in control steers (3.7 ng/ml) (pooled SEM = 0.7), but GH decreased (P < 0.001) after feeding in both groups. Iv injection of GHRH stimulated release of GH 1 hr before, but not when injected 1 hr after feeding (P < 0.001). In addition, net areas under the GH curve were not significantly different between control and alloxan-treated groups. We conclude that increased concentrations of insulin after feeding do not mediate feeding-induced suppression of GH secretion in steers.

Neuroregulation of growth hormone secretion in domestic animals.

Growth hormone (GH) is essential for postnatal somatic growth, maintenance of lean tissue at maturity in domestic animals and milk production in cows. This review focuses on neuroregulation of GH secretion in domestic animals. Two hormones principally regulate the secretion of GH: growth hormone-releasing hormone (GHRH) stimulates, while somatostatin (SS) inhibits the secretion of GH. A long-standing hypothesis proposes that alternate secretion of GHRH and SS regulate episodic secretion of GH. However, measurement of GHRH and SS in hypophysial-portal blood of unanesthetized sheep and swine shows that episodic secretion of GHRH and SS do not account for all episodes of GH secreted. Furthermore, the activity of GHRH and SS neurons decreases after steers have eaten a meal offered for a 2-h period each day (meal-feeding) and this corresponds with reduced secretion of GH. Together, these data suggest that other factors also regulate the secretion of GH. Several neurotransmitters have been implicated in this regard. Thyrotropin-releasing hormone, serotonin and gamma-aminobutyric acid stimulate the secretion of GH at somatotropes. Growth hormone releasing peptide-6 overcomes feeding-induced refractoriness of somatotropes to GHRH and stimulates the secretion of GHRH. Norepinephrine reduces the activity of SS neurons and stimulates the secretion of GHRH via alpha(2)-adrenergic receptors. N-methyl-D,L-aspartate and leptin stimulate the secretion of GHRH, while neuropeptide Y stimulates the secretion of GHRH and SS. Activation of muscarinic receptors decreases the secretion of SS. Dopamine stimulates the secretion of SS via D1 receptors and inhibits the secretion of GH from somatotropes via D2 receptors. Thus, many neuroendocrine factors regulate the secretion of GH in livestock via altering secretion of GHRH and/or SS, communicating between GHRH and SS neurons, or acting independently at somatotropes to coordinate the secretion of GH.

Prolactin does not enhance glucose-stimulated insulin release in red deer stags.

Red deer stags have a seasonal pattern of insulin secretion that is characterized by both elevated basal and glucose-stimulated insulin release in summer compared with winter. Since the seasonal timing of this pattern is similar to that of prolactin and growth rate, the objectives of this study were: first, to determine whether prolactin is associated with the enhanced secretion of insulin during the summer growth period, and second, to determine whether a chronic reduction in plasma prolactin levels would alter body composition. Prolactin was suppressed in plasma using a long-acting form of the dopamine agonist bromocriptine (parlodel LA), which was administered at one of four doses (0-0.3 mg/kg) to each of four groups of castrate stags. Bromocriptine was administered during two 6-wk periods; the first in winter and the second in summer. During the sixth wk of each period, each animal was given three IVGTT at the following glucose doses (10 mg/kg, 70 mg/kg, and 200 mg/kg). Two d later, ovine prolactin was administered to each animal (0.08 mg/kg) and a single IVGTT (70 mg/kg) was given 2 hr later. Body composition was determined by the tritriated water dilution method at the beginning and end of each 6-wk treatment. Chronic suppression of prolactin during winter or summer did not significantly alter the amount of insulin released after each IVGTT, nor did it significantly alter body composition. Furthermore, acute administration of prolactin did not significantly enhance the release of insulin following an IVGTT, during winter or summer treatment periods. It is concluded that elevated levels of prolactin in summer do not enhance the release of insulin to glucose in red deer. Furthermore, a reduction in growth rate following a reduction in plasma prolactin is not associated with a change in body composition.

Myostatin alters glucose transporter-4 (GLUT4) expression in bovine skeletal muscles and myoblasts isolated from double-muscled (DM) and normal-muscled (NM) Japanese shorthorn cattle.

The purpose of this study was to determine whether myostatin alters glucose transporter-4 (GLUT4) expression in bovine skeletal muscles and myoblasts isolated from double-muscled (DM) and normal-muscled (NM) Japanese Shorthorn cattle. Plasma concentrations of glucose were lower in DM cattle than in NM cattle (P < 0.01). The expression of GLUT4 messenger RNA (mRNA) in the skeletal muscle ex vivo and in myoblasts at 72 h after differentiation in vitro was higher in DM cattle than in NM cattle (P < 0.01). In contrast, the NM and DM cattle did not differ with respect to skeletal muscle expression of GLUT1 and myocyte enhancer factor-2c (MEF2c), a transcription factor of GLUT4. In differentiated myoblasts, the expression of GLUT1, GLUT4, and MEF2c mRNAs was greater in DM cattle than in NM cattle (P < 0.01). In the presence and absence of insulin, glucose uptake in myoblasts was increased in DM cattle relative to that of NM cattle (P < 0.01). The addition of myostatin decreased the expression of GLUT4 and MEF2c mRNAs in DM myoblasts (P < 0.05). Results of the present study suggest that myostatin inhibits the expression of GLUT4 mRNA possibly via MEF2c and that the greater ability of the DM cattle to produce muscle relative to the NM cattle may be due to their greater sensitivity to insulin and greater use of glucose.

Lack of association between allelic status and myostatin content in lambs with the myostatin g+6723G>A allele.

Lambs with the myostatin (MSTN) g+6723G>A mutation have a greater muscle mass, which is believed to be associated with reduced myostatin protein abundance. This experiment was designed to determine if differences in allelic frequency of the MSTN g+6723G>A mutation affected abundance of myostatin protein from birth to 24 wk of age. A Poll Dorset cross White Suffolk ram (MSTN A/G) was mated to 35 White Suffolk cross Border Leicester cross Merino ewes (MSTN A/G, n=21, and MSTN G/G, n=14). The progeny of these matings delivered 44 lambs with MSTN A/A (n=9), MSTN A/G (n=21), and MSTN G/G (n=14) genotypes. At approximately 1, 4, and 12 wk of age, a biopsy sample was collected and a blood sample was taken to measure the abundance of myostatin protein in muscle and plasma. At approximately 24 wk of age, the wether lambs were slaughtered to determine carcass characteristics and muscle samples were taken from the bicep femoris. The abundance of mature myostatin protein in muscle from 1 wk old lambs was less (P=0.05) in MSTN A/A and MSTN A/G compared with MSTN G/G lambs. However, at 4 and 24 wk the MSTN A/A lambs had a greater (P=0.04) abundance of myostatin protein compared with the MSTN A/G and MSTN G/G lambs. The abundance of mature myostatin did not differ between genotypes in plasma but the myostatin protein did increase as the lambs aged. At slaughter the MSTN A/A wether lambs had greater dressing percentages (P=0.04), shortloin (P=0.01), topside (P<0.001), and round (P=0.01) weights but did not differ in final BW or HCW (P>0.05). The MSTN A/A lambs had more muscle fibers (P=0.02) in the cross-section of LM between the 12th and 13th rib. The MSTN A/A lambs also had greater lean (P=0.002), less fat (P=0.009), and reduced organ (heart, liver, spleen, and kidneys) mass as determined by computed tomography scanning than MSTN G/G lambs. The results of this study demonstrated that lambs homozygous for the MSTN g+6723G>A mutation have changes in carcass characteristics (dressing and total lean), organ weights, and muscle fiber number. This may be due to reduced myostatin protein early in utero, but after 4 wk of age there was no difference in the abundance of mature myostatin protein in muscle or plasma among MSTN A/A, MSTN A/G, and MSTN G/G genotypes.