Growth hormone response to a novel growth hormone-releasing tripeptide in horses: interaction with gonadotropin-releasing hormone, thyrotropin-releasing hormone, and sulpiride

A series of experiments was performed to determine the factor(s) responsible for an apparent inhibition of GH secretion in mares administered the GH secretagogue EP51389 in combination with GnRH, thyrotropin-releasing hormone (TRH), and sulpiride. Experiment 1 tested the repeatability of the original observation: 10 mares received EP51389 at 10 microg/kg BW; five received TRH (10 microg/kg BW), GnRH (1 microg/kg BW), and sulpiride (100 microg/kg BW) immediately before EP51389, and five received saline. The mixture of TRH, GnRH, and sulpiride reduced (P = 0.0034) the GH response to EP51389, confirming the inhibitory effects. Experiment 2 tested the hypothesis that sulpiride, a dopamine antagonist, was the inhibitory agent. Twelve mares received EP51389 as in Exp. 1; six received sulpiride before EP51389 and six received saline. The GH responses in the two groups were similar (P > 0.1), indicating that sulpiride was not the inhibitory factor. Experiment 3 tested the effects of TRH and(or) GnRH in a 2 x 2 factorial arrangement of treatments. Three mares each received saline, TRH, GnRH, or the combination before EP51389 injection. There was a reduction (P < 0.0001) in GH response in mares receiving TRH, whereas GnRH had no effect (P > 0.1). Given those results, Exp. 4 was conducted to confirm that TRH was inhibitory in vivo as opposed to some unknown chemical interaction of the two compounds in the injection solution. Twenty mares received TRH or saline and(or) EP51389 or saline in a 2 x 2 factorial arrangement of treatments. Injections were given separately so that the two secretagogues never came in contact before injection. Again, TRH reduced (P < 0.0001) the GH response to EP51389. In addition, TRH and EP51389 each resulted in a temporary increase in cortisol concentrations. Experiment 5 tested whether TRH would alter the GH response to GHRH itself. Twelve mares received porcine GHRH at 0.4 microg/kg BW; six received TRH prior to GHRH and six received saline. After adjustment for pretreatment differences between groups, the GHRH-induced GH response was completely inhibited (P = 0.068) by TRH. Exp. 6 was a repeat of Exp. 5, except geldings were used (five per group). Again, pretreatment with TRH inhibited (P < 0.0001) the GH response to GHRH. In conclusion, TRH inhibits the GH response not only to EP51389 but also to GHRH in horses, and in addition to its known secretagogue action on prolactin and TSH it may also stimulate ACTH at the dosage used in these experiments.     

Use of growth hormone response to growth hormone-releasing hormone to determine growth potential in beef heifers.

The response of GH to GHRH at weaning is known to predict postweaning growth and body composition in beef bulls. The objective of this study was to determine whether GH response to a challenge of GHRH and plasma IGF-I can predict growth rate and body composition in the beef heifer. Growth hormone response to a challenge with two doses of GHRH was measured in 67 Angus heifers averaging 225 d of age (SD = 21) and 217 kg BW (SD = 32). Blood samples were collected at 0 and 10 min relative to an initial "clearance dose" (4.5 micrograms GHRH/100 kg BW) and again, 3 h later, relative to a challenge dose (1.5 or 4.5 micrograms GHRH/100 kg BW). Each animal received each of the two challenge doses, which were randomly assigned across 2 d of blood collection. Serum GH concentration was measured by RIA. Plasma was collected every 28 d during a 140-d growth test and assayed for IGF-I by RIA. Body weight was measured every 28 d and hip height was measured at weaning and at the end of a 140-d growth test. Average daily gain was calculated on d 140 of the growth test and body composition measurements were estimated by ultrasound 2 wk after completion of the growth test. Responses to the two GHRH challenges were dose-dependent (P < 0.05). Average daily gain tended to be related to GH response to the 1.5 micrograms GHRH/100 kg BW dose (R2 = 0.05; P = 0.06), but no relationship was observed at the 4.5 micrograms GHRH/100 kg BW dose (R2 = 0.00; P = 0.93). An inverse relationship (R2 = 0.06; P = 0.02) was observed between response to the 1.5 micrograms GHRH/100 kg BW dose and intramuscular fat percentage. Mean plasma IGF-I concentration was positively associated with ADG (R2 = 0.06; P < 0.01). Growth hormone response to GHRH is modestly related to body composition but not to ADG in weanling beef heifers and likely has limited use in evaluation of growth performance in replacement beef heifers.     

Growth hormone response to growth hormone-releasing hormone in beef cows divergently selected for milk production

In dairy cattle, increased circulating growth hormone has been associated with selection for greater milk yield. This study tested the hypothesis that beef cows divergently selected for milk production would have differing GH responses to a challenge dose of GHRH. Growth hormone response to a challenge of GHRH was measured in 36 Angus-sired cows ranging from 6 to 10 yr of age. The cows were classified as high milking (n = 16) or low milking (n = 20), on the basis of their sires' milk EPD. Mean milk EPD (in kilograms) were 16.6 and -14.4 for high and low milking cows, respectively. Milk production was estimated by the weigh-suckle-weigh procedure. Blood samples were taken immediately before and 10 min after a clearance dose of 4.5 microg of GHRH/100 kg BW (injected i.v.) and, 3 h later, immediately before and 10 min after a challenge dose of either 1.5 or 4.5 microg of GHRH/100 kg BW. Each animal received both challenge doses, and the doses were randomly assigned across 2 d of blood collection. Serum concentrations of GH and IGF-I were measured by RIA. Serum IGF-I was measured in the baseline blood sample on d 1 of blood collection. A positive relationship (r = 0.35; P = 0.03) was observed between the cows' rankings for each dose of GHRH; that is, high responders to the low dose were high responders to the high dose. Growth hormone response to the 4.5 microg/100 kg BW challenge dose of GHRH was positively related to sire milk EPD (R2 = 0.09; P = 0.03). Response of GH to the 1.5 microg GHRH/100 kg BW challenge dose also tended to be related (P = 0.08) to sire milk EPD of high milking cows. In addition, IGF-I concentrations of high milking cows were inversely related (R2 = 0.24; P = 0.04) to sire milk EPD. Growth hormone response to GHRH challenge may have potential as an additional tool in the evaluation of milk production in beef cattle.     

Predicting bull growth performance and carcass composition from growth hormone response to growth hormone-releasing hormone.

Development of practical, physiologically based methods that provide an early, yet accurate, evaluation of a bull's genetic merit could benefit the beef industry. The use of GH response to a single, acute dose of GHRH was evaluated as a predictor of future growth performance and carcass characteristics of weanling bulls. Fifty-six Angus bulls averaging 229 d (SD = 27) of age were administered three doses i.v. (0, 1.5, and 4.5 microg/100 kg BW) of human GHRH (1-29) analog in a Latin square design balanced for residual effects. Blood samples were collected via jugular catheter at -60, -45, -30, -15, 0, 5, 10, 15, 30, 45, 60, 90 and 120 min relative to GHRH injection. Serum concentrations of GH were plotted over time. Response to GHRH was calculated as the area under the GH response curve (AUC-GH) using the trapezoidal approximation. Relationships between AUC-GH, weaning weight adjusted to 205 d of age (205-d WW), and direct weaning weight EPD (WWEPD) versus age-adjusted BW (BWadj), ADG, and carcass measurements from a 140-d growth performance test were evaluated using simple linear regression. A positive correlation between AUC-GH and ADG and an inverse relationship between AUC-GH and carcass fat were observed. The present study provides evidence that AUC-GH is a better predictor of future growth performance in beef bulls than 205-d WW or WWEPD values. Thus, GH response to GHRH is associated with subsequent growth and may be a useful tool for sire selection in beef production.     

Relation of growth hormone response to growth hormone-releasing hormone before weaning and postweaning growth performance in beef calves

Previously, GH response to GHRH challenge at weaning has been shown to be indicative of ADG during a standard postweaning growth performance test in Angus cattle. In this study, we tested the hypothesis that GH response to GHRH before weaning would predict postweaning ADG. Bulls with the highest and lowest GH responses to GHRH over a 3-yr period, relative to their contemporaries, were used as sires, to allow for examination of the persistence of GH response to GHRH through selection. The selected calves in this study were sired by one of four Angus bulls chosen based on their GH response to GHRH (high response, n = 2; low response, n = 2). Forty-nine Angus calves (bulls, n = 24; heifers, n = 25) were challenged with GHRH at approximately 60, 105, and 150 d of age and at weaning (219 d; SD = 25). Blood samples were taken immediately prior to and 10 min following an i.v. clearance dose of 4.5 microg of GHRH/100 kg BW and, 2 h later, immediately prior to and 10 min following a challenge dose of either 1.5 or 4.5 microg of GHRH/100 kg BW. Two hours later, the procedure was repeated, with each calf receiving the other challenge dose. Body weight was measured every 28 d and ADG was calculated over a 140-d growth performance test (heifers and bulls maintained separately). Data were log-transformed for statistical analyses. In the selected bulls and heifers, response of GH to 1.5 microg of GHRH/100 kg BW at 60 and 105 d of age was positively related (P < 0.05) to postweaning ADG. Response to 4.5 microg of GHRH/100 kg BW at 105 d of age and at weaning was positively related (P < 0.01) to postweaning ADG. Inclusion of sire in the analysis improved the relationship between GH response and ADG for calves of sires with high GH responses from R2 = 0.18 (P = 0.01) to R2 = 0.33 (P = 0.02). When the GH response to GHRH of the unselected calves at weaning was added to the data from the selected animals and analyzed, the GH response of the bulls was related to postweaning ADG (R2 = 0.09; P = 0.04). In conclusion, GH response to GHRH as early as 60 d of age is indicative of postweaning ADG in beef cattle. In addition, the relationship between GH response to GHRH and postweaning ADG is improved with selection for greater GH response to GHRH.     

Associated luteinizing hormone-releasing hormone and luteinizing hormone secretion in ovariectomized gilts.

The secretion of luteinizing hormone-releasing hormone (LHRH) and its temporal association with pulses of luteinizing hormone (LH) was examined in ovariectomized prepuberal gilts. Push-pull cannulae (PPC) were implanted within the anterior pituitary gland and LHRH was quantified from 10 min (200 microliters) perfusate samples. Serum LH concentrations were determined from jugular vein blood obtained at the midpoint of perfusate collection. Initial studies without collection of blood samples, indicated that LHRH secretion in the ovariectomized gilt was pulsatile with pulses comprised of one to three samples. However, most pulses were probably of rapid onset and short duration, since they comprised only one sample. Greater LHRH pulse amplitudes were associated with PPC locations within medial regions of the anterior pituitary close to the median eminence. In studies which involved blood collection, LH secretion was not affected by push-pull perfusion of the anterior pituitary gland in most gilts, however, adaptation of pigs to the sampling procedures was essential for prolonged sampling. There was a close temporal relationship between perfusate LHRH pulses and serum LH pulses with LHRH pulses occurring coincident or one sample preceding serum LH pulses. There were occasional LHRH pulses without LH pulses and LH pulses without detectable LHRH pulses. These results provide direct evidence that pulsatile LHRH secretion is associated with pulsatile LH secretion in ovariectomized gilts. In addition, PPC perfusion of the anterior pituitary is a viable procedure for assessing hypothalamic hypophyseal neurohormone relationships.     

Growth hormone secretory responsiveness to multiple injections of growth hormone-releasing factor in sheep

Growth hormone releasing factor (GRF) has been shown to be a potent and specific stimulant of growth hormone (GH) secretion in a variety of species. The objective of this series of experiments was to determine whether repeated iv bolus injections of GRF would increase circulating levels of GH, and thus have the potential to stimulate growth in young lambs. In lambs given three injections of hpGRF either one (.065 nmol/Kg) or two hours apart (.016 or .065 nmol/Kg), the GH secretory responses decreased significantly with each subsequent injection. Bolus injections of hpGRF (.016 nmol/Kg) given for three days in 15 Kg lambs resulted in development of refractoriness to subsequent injections. In lambs treated three and six times daily, basal plasma GH and SmC levels decreased progressively over the three day period. Older lambs (30 Kg) also became less responsive to hpGRF given once daily for three days, but the refractoriness was less pronounced than in 15 Kg lambs. In 30 Kg lambs treated once daily with bovine GRF (bGRF, .065 nmol/Kg), GH secretory responsiveness decreased progressively over a five day treatment period. Because of the severe refractoriness to GRF that developed in very young lambs, it was predicted that multiple injections over several weeks might result in suppression of growth. However, growth rate, feed intake and feed efficiency were not altered in 10 Kg lambs treated twice daily for three weeks with .065 nmol/Kg bGRF and there was no evidence of refractoriness to bGRF as determined every seven days. These results suggest that the refractoriness that develops with multiple bolus injections of GRF may not be long-lasting, and therefore will not have a negative impact on growth. However, there was no evidence that at the frequencies tested bolus injections of GRF could stimulate growth in young lambs.     

Thermoregulation of the testicle in response to exercise and subsequent effects on semen characteristics of stallions

Stallions (n = 8) were implanted with a thermal sensory device in the muscle of the neck and the subcutaneous tissue of the scrotum and then assigned to either a nonexercise (Non-EX; n = 4) or exercise (EX; n = 4) group. A motorized equine exerciser was used to work EX stallions 30 min/d for 4 d/wk during a 12-wk period from July through October 2010. Temperatures (subcutaneous scrotal, intramuscular neck, and rectal) were recorded at 0, 22, and 30 min after the start of exercise, as well as 60 and 120 min post-exercise. Hourly ambient temperature and relative humidity data were also obtained. Semen was collected at 0, 4, 8, and 12 wk and analyzed for volume, sperm concentration, total sperm numbers, percentages of total and progressively motile sperm, sperm morphologic characteristics, and sperm DNA quality. No effect (P > 0.05) of exercise was observed on any of the measured semen variables. Implantation of thermal sensory devices had no demonstrable acute or chronic effects on the scrotal or neck tissue, indicating that the thermal sensory devices are a safe and effective way to measure subcutaneous scrotal and neck temperatures. At 22 and 30 min of exercise, rectal and neck temperatures increased (P < 0.0001) approximately 1.9 and 2.4°C, respectively, and scrotal temperatures simultaneously increased, although not significantly (P = 0.33), approximately 0.8°C. Correlations existed between scrotal, neck, rectal, and ambient temperatures, with the correlation between scrotal and rectal temperatures being greatest (r(s) = 0.76; P < 0.0001). Although moderate exercise for a short duration in extreme heat and humidity did significantly increase core body temperatures in stallions, scrotal temperatures did not significantly increase, and sperm parameters were unaffected.     

Serum growth hormone release in response to a growth hormone-releasing factor analog during and after anesthesia in pigs.

The objective of this study was to evaluate the time course for full recovery of the growth hormone governing system and somatocrinin response after anesthesia. Sixteen Yorkshire gilts aged 32 weeks were divided into three groups: saline (n = 6), anesthesia + saline (n = 5) and anesthesia + somatocrinin (n = 5). Under anesthesia, the area under the growth hormone curve was increased (P less than 0.05) from 1172 +/- 184 to 2807 +/- 1002 ng.min.mL-1, and a more consistent growth hormone response to somatocrinin was observed; all animals responded immediately, while only three out of five did so four hours before anesthesia. Sixteen and 40 hours after anesthesia, basal and stimulated growth hormone levels were comparable to those of unanesthetized controls, suggesting a prompt recovery from the effects of anesthesia. These data indicate that anesthetized pigs release higher quantities of growth hormone and have a more consistent growth hormone response to somatocrinin. A full recovery of basal and somatocrinin-induced growth hormone release was observed as soon as 16 hours after anesthesia.     

Androgen and estradiol effects on gonadotropin secretion and response to GnRH in ovariectomized pony mares

In Exp. 1, 16 long-term ovariectomized pony mares were used to determine the effects of treatment with estradiol benzoate (EB) and dihydrotestosterone (DHT) benzoate alone, and in combination, on secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in daily blood samples and after three consecutive injections of gonadotropin releasing hormone (GnRH). Administration of EB alone, or in combination with DHT, every other day for 11 d reduced (P less than .05) concentrations of FSH and increased (P less than .05) concentrations of LH in daily blood samples, and increased (P less than .05) the secretion of both gonadotropins after administration of GnRH. Treatment with DHT alone had no effect (P greater than .10) on LH or FSH concentrations in daily blood samples and no effect on the LH response to exogenous GnRH. There was no interaction (P greater than .10) between DHT and EB treatment for any hormonal characteristic. In Exp. 2, the control mares and mares treated with DHT in Exp. 1 were equally allotted to treatment with vehicle or testosterone propionate (TP) every other day for six injections, and then GnRH was administered as in Exp. 1. Treatment with TP had no effect (P greater than .10) on LH or FSH concentrations in daily blood samples but increased (P less than .05) the FSH response to exogenous GnRH, confirming our findings in previous experiments. It is concluded that the TP-induced stimulation of FSH secretion after exogenous GnRH in ovariectomized mares may involve estrogens produced from aromatization of the injected androgen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of growth hormone-releasing hormone and somatostatin from perifused,bovine hypothalamic slices. III. Reciprocal feedback between growth hormone-releasing hormone and somatostatin

An in vitro perifusion system for bovine hypothalamic tissue was used to determine if growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) modulate each other's release, and whether SRIF mediates D₁-agonist-induced suppression of GHRH in cattle. Up to three sagittal slices (600 μm) of bovine hypothalamus, immediately parallel to the midline, were cut in an oxygenated balanced salt solution at 4° C, placed in 5 cc syringe barrels, and perifused at 37° C with oxygenated minimum essential medium-α at a flow rate of 0.15 ml/min. Three experiments were conducted, and medium effluent was collected every 20 min before (two samples), during (one or three samples), and after (six samples) treatment. Areas under GHRH and SRIF response curves (AUC), adjusted by covariance for pretreatment values, were calculated from samples collected during the treatment/post-treatment period. Perifusion of SRIF at 10⁻⁶ M and 10⁻⁴ M decreased AUC for GHRH from 86.3 (control) to 65.4 and 59.5 ± 6.3 ng · ml⁻¹ min, but 10⁻⁸ M SRIF was ineffective. Relative to controls, 10⁻⁸, 10⁻⁶, and 10⁻⁴ M GHRH increased release of SRIF 190, 675, and 1,135%, respectively. Activation of D₁ receptors with 10⁻⁶ M SKF 38393 increased AUC for SRIF from 12.5 ng · ml⁻¹ min (control) to 484.9 ng · ml⁻¹ min and decreased AUC for GHRH from 36.4 ng · ml⁻¹ min (control) to 18.2 ng · ml⁻¹ min. Blockade of SRIF action with a SRIF antagonist, cyclo-[7-aminoheptanoyl-phe-d-trp-lys-thr(bzl)], increased release of GHRH 1.9-fold. In addition, the SRIF antagonist blocked SKF 38393-induced suppression of GHRH. We concluded that GHRH and SRIF interact within the bovine hypothalamus/pituitary stalk to modulate the release of the other. Moreover, SRIF mediates the inhibitory effects of activation of D₁ receptors on release of GHRH in cattle.     

Growth hormone releasing factors and secretion of growth hormone in sheep,calves and pigs

Human pancreatic growth hormone releasing factors (hpGRF) (1–40) and (1–44) were administered iv in sheep, pigs and calves to determine their effectiveness in stimulating GH release in these species. Both peptides produced a rapid increase in plasma GH concentration in all three species at dose levels ranging from .0065 to .65 nmol/kg. Moreover, there was no difference in the GH-secretory response observed between hpGRF(1–44)NH₂ and (1–40)OH in sheep. Sheep also responded to hpGRF(1–40)NH₂ and (1–40)OH as well as [his₁]- and [tyr₁]-hpGRF(1–40)NH₂ in a similar manner. Rat hypothalamic GRF was less effective than [his₁]-hpGRF(1–40), while the response to bGRF was not significantly different from hpGRF(1–40) in stimulating GH secretion in sheep. Although all three species responded to hpGRF, the elevation in plasma GH levels above baseline were greater after hpGRF injection in sheep than in pigs or calves. Subcutaneous injection of hpGRF in sheep was an effective mode of administration of the peptide, although the effect was not as long-lasting as that after iv injections and higher doses were required to stimulate GH secretion.     

Relation of growth hormone response to growth hormone-releasing hormone to estimation of milk production via deuterium oxide dilution in beef cattle

Current methods of estimating milk production in beef cows can be time-consuming, labor-intensive, and subject to high variability. The weigh-suckle-weigh (WSW) method requires repeated separation of offspring from their dams. Machine milking requires that animals be acclimated to the equipment prior to the estimation. The objective of Exp. 1 was to validate a deuterium oxide (D2O) dilution method of estimating milk production in cattle. In Exp. 1, Holstein calves (n = 5) averaging 29+/-2 d of age and 52.6+/-2.5 kg (+/- SE) were used as the model. Blood was collected for baseline D2O measurements followed by an injection of 300 mg D2O/kg BW. Syringes were weighed before and after the injection to gravimetrically determine the dose. Another blood sample was collected after D2O was allowed to equilibrate with body water for 2 h, and on each of the next five consecutive days, prior to feeding. Actual milk intake was measured by disappearance (i.e., amount of milk replacer offered to the calf minus the amount refused). Deuterium oxide in plasma was measured by mass spectrometry and milk intake was computed from the disappearance curve of D2O in blood plasma for each calf. Accumulated milk intake estimated by D2O dilution was highly correlated (y = 0.9x + 0.6; R2 = 0.99; P < 0.001) with actual milk intake. The objectives of Exp. 2 were to determine whether 1) D2O dilution was comparable to a standard measure of milk production in beef heifers and 2) growth hormone (GH) response to GH-releasing hormone (GHRH) in heifers at weaning is predictive of subsequent milk production. Deuterium oxide dilution and WSW were compared using 14 first-calf Angus heifers and their calves. Deuterium oxide dilution was used to estimate milk production of 40 first-calf Angus heifers that had been challenged with GHRH at weaning. Results indicate that the D2O dilution method is correlated (R2 = 0.89; P = 0.04) to the WSW estimation of milk production. Growth hormone response to GHRH in weanling heifers is positively related (R2 = 0.22; P = 0.03) to their subsequent milk production. Deuterium oxide dilution in calves offers an additional approach to the estimation of milk production of the dam in typical beef cattle production settings.     

Effects of human pancreatic and rat hypothalamic growth hormone-releasing factors on growth hormone secretion in steers

Potencies of human pancreatic growth hormone-releasing factor [hpGRF(1–40)-OH] and of a peptide corresponding to the N-terminal 29 residues of rat hypothalamic GRF, [rGRF(1–29)-NH₂] were compared in two experiments. Eight Angus steers averaging 297 days of age and 290 kg in February 1984 were used in Exp. 1. Five months later six of the steers, weighing 391 kg, were used in Exp. 2.In Exp. 1, hpGRF(1–40)-OH and rGRF(1–29)-NH₂ were infused for 5 min at rates of 0, 1.3, 2.6, 5.2, 7.8 and 13.3 pmol/min/kg. Two steers were infused simultaneously, one received hpGRF(1–40)-OH and the other the equivalent dose of rGRF(1–29)-NH₂. Four pairs of steers received each dose. Both peptides elicited rapid GH release. Plasma GH concentrations peaked 15 to 20 min following onset of GRF administration, and returned to baseline levels 60 to 90 min later. Minimum effective doses, the lowest dose tested that resulted in a statistically significant GH reponse, were 5.2 pmol/min/kg hpGRF(1–40)-OH and 13.3 pmol/min/kg rGRF(1–29)-NH₂. Magnitudes of GH responses to 5.2, 7.8 and 13.3 pmol/min/kg hpGRF(1–40)-OH and 13.3 pmol/min/kg rGRF(1–29)-NH₂ were similar; corresponding to respective peak concentrations of 79, 66, 57 and 56 ng/ml. Growth hormone levels before GRF administration averaged 16 ng/ml.Experiment two was designed like the first except steers were infused for 6 hr with hpGRF(1–40)-OH and rGRF(1–29)-NH₂ at rates of 0, .5 and 1 pmol/min/kg. Both peptides at both rates raised (P<.05) GH concentrations during the 6 hr infusion period. Mean GH levels were 7 ng/ml during saline infusion, 30 and 23 ng/ml during infusion of .5 pmol/min/kg hpGRF(1–40)-OH and rGRF(1–29)-NH₂, and 41 and 27 ng/ml during infusion of 1 pmol/min/kg of the respective peptides. The initial GH response was biphasic, after which GH levels decreased temporarily and then one or two more GH surges occurred during the latter portion of the infusion period. Results demonstrate that hpGRF(1–40)-OH and rGRF(1–29)-NH₂ are potent GH secretagogues in steers. Potency of rGRF(1–29)-NH₂ is about 40% of hpGRF(1–40)-OH. Intrinsic activities, their ability to stimulate maximum GH secretion, appear to be similar. Both peptides are effective in raising GH levels over a 6 hr constant infusion period.     

Effect of betaine on growth hormone pulsatile secretion and serum metabolites in finishing pigs

An experiment was conducted to investigate the effect of dietary betaine (0%, 0.125%) on growth performance, growth hormone (GH) pulsatile secretion and serum metabolites in crossbred finishing pigs. Three replications of eight pigs (four barrows and four gilts) were used for each treatment, and blood samples for the determination of GH pulsatile secretion were collected every 15 min for 3 h. The results showed that betaine supplementation resulted in 5.45% (p<0.05) increase in average daily gain, whereas average daily feed intake and feed to gain ratio were not affected. Serum basal GH level, mean GH level and GH pulse amplitude were elevated by 41.79% (p<0.01), 48.98% (p<0.01) and 35.05% (p<0.05), respectively, with betaine treatment, but GH pulse frequency and pulse duration remained unchanged (p>0.05). Serum urea nitrogen concentration in pigs fed betaine was 21.58% lower than that of controls (p<0.01), whereas total protein level was significantly increased with betaine supplementation (p<0.05). The study suggests that betaine could promote growth by enhancing GH secretion in finishing pigs.     

Neuroendocrine regulation of growth hormone secretion in sheep. V. Growth hormone releasing factor and thyrotrophin releasing hormone.

The effects of intravenous (IV) and intracerebroventricular (ICV) administration of either bovine growth hormone releasing hormone (GRF) or thyrotrophin releasing hormone (TRH) on plasma growth hormone (GH) and glucose levels have been examined in sheep. Intravenous GRF 1-29NH2 at 3 and 30 micrograms stimulated an increase in GH levels in a dose-dependent fashion; administration of GRF into a lateral cerebral ventricle, however, produced a smaller GH response which was similar at these two doses. Evaluation of somatostatin levels in petrosal sinus blood (which collects pituitary effluent blood) showed that ICV administration of GRF stimulated a release of somatostatin into the blood. Furthermore, concurrent administration of GRF and a potent anti-somatostatin serum ICV resulted in a much enhanced release of GH which was similar to that obtained with a comparable dose of GRF given IV. TRH (as another putative GH-secretagogue) was also administered both IV and ICV. When given IV, 200 micrograms (but not 100 micrograms) TRH produced an elevation in GH levels. By contrast, when 5 micrograms TRH was given ICV there was a decrease in circulating GH levels, but no change in plasma somatostatin concentrations. These results indicate that the smaller GH response to ICV- compared with IV-administered GRF is due to the release of somatostatin within the brain. In addition, it would seem that TRH is not a physiological GH-secretagogue in sheep.     

A two-sample method for assessing growth hormone response to growth hormone-releasing hormone challenge: use as a predictor of gain in beef bulls

In two experiments, Black Angus bulls were challenged at weaning with GHRH analog and evaluated for their GH response to determine whether GH response can predict subsequent growth characteristics. The GH response was determined by measuring GH in blood serum collected 0 and 10 min after GHRH injection (Exp. 1: 1.5 microg/100 kg BW human GHRH, n = 34; Exp. 2: 1.5 and 4.5 microg/100 kg BW bovine GHRH [treatments LGHRH and HGHRH, respectively] administered 3 h after a 4.5 microg/100 kg BW "clearance dose" of GHRH, n = 38]. In Exp. 1, GH response did not predict growth or carcass measurements. In Exp. 2, GH response to LGHRH was positively related to ADG (R2 = .18; P = .007) during a 112-d controlled feeding trial. In addition, there was a tendency for bulls with a greater GH response to HGHRH to exhibit greater ADG than animals with a low response. However, GH response to GHRH was not related to changes in hip height (HH) or carcass ultrasound measurements at d 112 of the growth performance trial. Response of GH to repeated GHRH challenges was consistent within animal over time (r = .47; P = .003). The use of a clearance dose 3 h prior to GHRH challenge improved the relationship between GH response and ADG. Results of this study suggest that GH response to GHRH challenge is a useful tool for identifying beef bulls with superior growth potential.     

Thyroid stimulating hormone and prolactin secretion after thyrotropin releasing hormone administration to mares: Dose response during anestrus in winter and during estrus in summer

The response of thyroid stimulating hormone (TSH) and prolactin (PRL) concentrations to administration of thyrotropin releasing hormone (TRH) was determined in light-horse mares during the anestrous season (winter) and during estrus (standing heat) in the summer. Within each season, mares (4/group) were treated with either saline (controls) or one of four doses of TRH (80, 400, 2,000 or 10,000 ug) intravenously. Samples of blood were drawn at −15, −.5, 15, 30, 45, 60, 90, 120, 180 and 240 min relative to TRH injection. Concentrations of TSH and PRL in pre-TRH samples were greater (P<.05) in anestrous mares during winter than in estrous mares during summer. Concentrations of TSH increased (P<.05) within 30 min after administration of TRH and remained elevated during the 4-hr sampling period. The maximal net change in TSH concentrations and the area under the response curve were greatest for 2,000 ug of TRH; 80 ug did not produce a significant TSH response. There was no interaction (P >.10) between reproductive state and TRH dose for TSH concentrations. Concentrations of PRL were not significantly affected by any TRH dose during either season. It appears that mares differ from many mammalian species in that they do not respond to an injection of TRH with increases in both TSH and PRL.     

Luteinizing hormone secretion in hypophysial stalk-transected gilts given hydrocortisone acetate and pulsatile gonadotropin-releasing hormone.

The site within the hypothalamic-pituitary axis at which cortisol acts to inhibit luteinizing hormone (LH) secretion was investigated in female pigs. Six ovariectomized, hypophysial stalk-transected (HST) gilts were given 1 microgram pulses of gonadotropin releasing-hormone (GnRH) iv every 45 min from day 0 to 12. On days 6-12, each of 3 gilts received either hydrocortisone acetate (HCA; 3.2 mg/kg body weight) or oil vehicle im at 12-hr intervals. Four ovariectomized, pituitary stalk-intact gilts served as controls and received HCA and pulses of 3.5% sodium citrate. Jugular blood was sampled daily and every 15 min for 5 hr on days 5 and 12. Treatment with HCA decreased serum LH concentrations and LH pulse frequency in stalk-intact animals. In contrast, serum LH concentrations, as well as the frequency and amplitude of LH pulses, were unaffected by HCA in HST gilts and were similar to those observed in oil-treated HST gilts. We suggest that chronically elevated concentrations of circulating cortisol inhibit LH secretion in pigs by acting at the level of the hypothalamus.     

Patterns of secretion of luteinizing hormone, follicle stimulating hormone and testosterone in stallions during the summer and winter

Samples of jugular blood were drawn from each of five stallions every 15 min for 12 h during the summer and winter to determine the short-term fluctuations in plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone. Concentrations of LH and FSH were generally not pulsatile, although one stallion exhibited three distinct pulses in these hormones during the winter. In general, patterns of secretion of all three hormones were similar in both seasons and the number of significant rises in hormonal concentrations did not differ between seasons. Concentrations of LH and FSH were positively correlated (P less than .05) for eight of the ten sampling periods, indicating a close relationship between the secretion rates of these two gonadotropins. Testosterone concentrations varied in an episodic manner during the 12-h period, and all stallions exhibited at least one episode of high testosterone secretion regardless of the pattern of LH concentrations. The response in testosterone concentrations to the three LH pulses exhibited by the one stallion in winter was not the same for each pulse. The correlations between a single random sample and mean concentrations over the 12-h period were high (r between .88 and .99) for all three hormones, indicating that a single sample of blood would be representative of overall concentrations. It appears that the stallion differs from males of other domestic species in that concentrations of gonadotropins and testosterone vary in a much less pulsatile manner.