Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine

The experiments were conducted to determine the effects of the administration of growth hormone-releasing peptide-2 (GHRP-2, also named KP102), both orally by gavage and in feed, on the release of growth hormone (GH) in swine and to investigate whether attenuation of the GH response occurs after short-term treatment with the peptide in feed. In the first experiment, saline or GHRP-2 at doses of 1, 4.5 and 9 mg/kg body weight (BW) was dissolved in 15 ml saline and administered orally as a bolus by gavage to cross-bred castrated male swine (n = 6). Orally administered GHRP-2 stimulated dose-related increases in peak concentrations of GH, with a return to basal by 120 min. After administering GHRP-2 orally, peak concentrations of GH and areas under the GH response curves (GH AUCs) for 180 min were higher (P < 0.05) than those in saline controls. In Experiment 2, GHRP-2 at doses of 0 (served as control), 1, 4.5 and 9 mg/kg BW was mixed in 150 g of feed and offered to cross-bred castrated male swine (n = 6) at 0900 hr and 1700 hr daily for a 3-d period. Administration of 1 mg/kg BW GHRP-2 to swine in feed failed to stimulate the release of GH, but GHRP-2 at doses of 4.5 and 9 mg/kg BW significantly (P < 0.05) increased plasma concentrations of GH after initial and final treatments at 0900 hr on Days 1 and 3 of treatment, respectively. Peak concentrations of GH and GH AUCs for 180 min after the initial and final treatments in the 4.5 and 9 mg/kg BW GHRP-2-treated swine were higher (P < 0.05) than those in controls. After 3 d of treatment with GHRP-2 in feed at doses of 4.5 and 9 mg/kg BW, GH responses to the peptide were maintained. The results of the present study indicate that the administration of GHRP-2 orally by gavage and in feed stimulates the release of GH in swine, and that the GH-releasing effect of the peptide does not become desensitized after short-term administration in feed.     

Effect of atropine and pyridostigmine on growth hormone response to GH-releasing peptide-2 and GH-releasing hormone in swine

To investigate the effects of high and low somatostatinergic tone on GH-releasing peptide-2 (GHRP-2) and GH-releasing hormone (GHRH)-induced growth hormone (GH) secretion in swine, we examined GHRP-2- and GHRH-induced GH secretion after pretreatment with atropine or pyridostigmine. Pretreatment of swine with atropine (80 µg/kg bodyweight (BW), intravenous (i.v.)) 15 min before i.v. administration of saline, GHRP-2 (30 µg/kg BW), GHRH (1 µg/kg BW) or a combination of GHRP-2 and GHRH, reduced plasma GH area under the curve ( P  < 0.05), completely blocked GH response to GHRH, and attenuated GH response to GHRP-2 and GHRH combined ( P  < 0.05), without affecting GH response to GHRP-2 only. A synergistic effect of GHRP-2 and GHRH was not observed. In contrast, pretreatment of swine with pyridostigmine (100 µg/kg BW, i.v.), under the same pretreatment conditions as above, increased plasma GH concentration ( P  < 0.01), augmented GH response to GHRP-2 ( P  < 0.05), and GHRP-2 and GHRH combined ( P  < 0.05), but did not affect GH response to GHRH. These results suggest that the cholinergic muscarinic agents atropine and pyridostigmine modulate the GH response to GHRP-2 and GHRH, and that GHRP-2 acts antagonistically on the inhibitory effect of somatostatin in swine.     

Role for des-acyl ghrelin in the responsiveness of plasma hormones and metabolites to ghrelin in Holstein steers

Gastric-derived peptide hormone ghrelin is known for its potent growth hormone (GH) stimulatory effects. The acyl-modification on N-terminal Ser(3) residue is reported to be important to stimulate the ghrelin receptor, GH secretagogue-receptor type1a (GHS-R1a). However, major portion of circulating ghrelin lacks in acylation, and some biological properties of des-acyl ghrelin have been reported in monogastric animals. In the present study, the responsiveness of plasma hormones and metabolites to ghrelin in steers was characterized, and role for des-acyl ghrelin in these changes was investigated. The repeated intravenous administrations of bovine ghrelin (1.0 microg/kg BW) every 2h for 8h to Holstein steers significantly increased the plasma acylated ghrelin, total ghrelin, GH, insulin and NEFA levels. The GH responses in peak values and area under the curves (AUCs) were attenuated by repeated injections of ghrelin, however, the responses of plasma total ghrelin were similar. Plasma insulin AUC decreased after fourth injection of ghrelin while plasma NEFA AUCs gradually increased by repeated injections of ghrelin. Pretreatment of des-acyl ghrelin (10.0 microg/kg BW) 5 min prior to the single injection of ghrelin (1.0 microg/kg BW) did not affect the ghrelin-induced hormonal changes. Moreover, the responses of plasma GH to bovine and porcine ghrelin, which differ in C-terminal amino acid residues, were similar in calves. These data show that (1) GH release was attenuated by repeated administration of ghrelin, (2) ghrelin regulates glucose and fatty acid metabolism probably via different pathway, and (3) des-acyl ghrelin is unlikely the antagonist for ghrelin to induce endocrine effects in Holstein steers.     

Oral administration of peptidergic growth hormone (GH) secretagogue KP102 stimulates GH release in goats

To assess the oral activity of KP102 (also known GHRP-2) on growth hormone (GH) release in ruminant animals, 5 or 10 mg/kg body weight (BW) of KP102 dissolved in saline was orally administered twice at 2 hr-intervals to either 1- or 3-mo-old goats (n = 5-6). Plasma GH concentrations in the 1-mo-old goats were elevated at 15 min after the first administration of both 5 and 10 mg/kg BW of KP102. Significant elevation of GH concentrations continued until 180 min after 10 mg/kg BW of KP102, whereas the elevated GH levels after the administrations of 5 mg/kg BW of KP102 subsided to basal concentrations within 90 min. The second administration of 10 mg/kg BW of KP102 failed to elevate the GH concentration, but 5 mg/kg BW of KP102 abruptly stimulated GH release. Plasma GH concentrations in the 3-mo-old goats were also significantly elevated after the administration of both 5 and 10 mg/kg BW of KP102. The plasma GH responses to 5 and 10 mg/kg BW of KP102 were almost identical. The elevated GH levels after the first administration of KP102 tended to be maintained throughout the experiment, and a transient increase in plasma GH levels was observed after the second administration. However, the stimulatory effect of KP102 on GH release in the 3-mo-old goats was small and less abrupt than that in the 1-mo-old goats. The concentrations of insulin-like growth factor-I were not increased by KP102 during the brief sampling periods used in this experiment. These results show that the oral administration of the peptidergic GH secretogogue KP102 stimulates GH release in a ruminant species, and that the oral activity of KP102 on GH release is modified by the age.     

Effects of dietary protein and growth hormone-releasing peptide (GHRP-2) on plasma IGF-1 and IGFBPs in Holstein steers

This study was conduct to determine the influence of dietary protein on the response of plasma insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) to exogenous growth hormone releasing peptide-2 (GHRP-2 or KP 102) in Holstein steers. Eight 16-month-old Holstein steers were grouped by liveweight to two feeding treatments; high protein (HP; CP 1.38 kg/day and TDN 4.5 kg/day DM intake, n=4) or low protein (LP; CP 0.66 kg/day and TDN 4.42 kg/day DM intake, n=4). The experiment was a single reverse design whereby each group was injected twice daily with GHRP-2 (12.5 microg/kg body weight (BW)/day) or saline solution into the jugular vein for a 6-day period. Plasma IGF-1 in the HP group were higher than in the LP group (P<0.05), but plasma 34 kDa IGFBP-2 was lower in the HP than the LP group (P<0.05). The amplitude of the maximum growth hormone (GH) peaks responding to GHRP-2 injection were higher at day 1 than at day 6 of saline or GHRP-2 treatment in both LP and HP steers (P<0.05). The area under the GH response curve for 180 min after the GHRP-2 injection was not significantly different between the LP and the HP groups at days 1 and 6. A response in plasma IGF-1 concentration to GHRP-2 treatment in the HP group was observed at day 1 (198.9+/-18.1 ng/ml), day 2 (195.2+/-21.1 ng/ml) and day 6 (201.3+/-14.8 ng/ml) (P<0.05). No increase in plasma IGF-1 was observed from GHRP-2 administration in the LP group. Although the response of plasma IGF-1 concentration to GHRP-2 administration was increased in the HP group (P<0.05), there was no apparent effect of GHRP-2 treatment on plasma 38-43 kDa IGFBP-3 and 34 kDa IGFBP-2 at days 2 and 6 of treatment. In conclusion, it is proposed that the 34 kDa IGFBP-2 is sensitive to dietary protein level and may play an important role in the regulation of circulating IGF-1 in ruminant. In addition, increased plasma IGF-1 concentration observed in the HP group in response to the GHRP-2 treatment did not appear to affect plasma IGFBPs.     

生长激素释放肽-2对猪生长性能、背膘及氮利用率的影响

选择体重(33±2)kg的DLY猪20头,随机分成4组,每组5头,分别以0、3、9、27μg/kgBW的剂量每日肌肉注射GHRP-228d。在试验的第3周进行4d的代谢试验;在第4周末测量活体背膘和眼肌厚度。结果表明:在第1周末随着剂量的增加,猪的日增重在处理组较对照组分别提高了10.51%、12.06%、16.21%(P<0.05);28d的平均日增重在处理组分别提高了4.5%、1.27%、8.99%(p<0.05)。饲料氮在第3周的消化率各组分别为82.92%、81.29%、82.3%、85.15%;代谢率52.59%6、51.8%、53.20%、56.67%。GHRP-2处理组有减少背膘和增加眼肌厚度的趋势。在试验条件下,以27μg/kgBW的剂量每日肌肉注射GHRP-22周可显著提高生长猪日增重,采食量在整个试验期处理组间无差异;连续处理的第3周出现生长抑制现象,其机理有待于进一步研究。     

Plasma growth hormone (GH) responses after administration of the peptidergic GH secretagogue KP102 into the oral cavity, rumen, abomasum and duodenum in adult goats

The study was performed to determine whether orally administered KP102 (also known as GHRP-2) stimulates GH release in adult goats, and how the orally administered KP102 passes through the digestive tract and stimulates GH release in ruminant animals. Five mg/kg body weight (BW) of KP102 dissolved in 9 ml of saline were administered into the oral cavity, rumen, omasum and duodenum of adult goats, and GH release after administration of KP102 was examined. The GH levels were significantly elevated at 20 min after administration of KP102 into the oral cavity, and plasma concentrations of GH remained significantly elevated until 60 min (P < 0.05). The GH levels after administration of KP102 into the abomasum were variable. However, the GH level tended to increase within 30 min after administration, and were significantly higher than those of controls after 120 to 150 min (P < 0.05). The GH levels after administration of KP102 into the duodenum were significantly elevated at 40 min after administration, and plasma concentrations of GH remained significantly elevated until 140 min (P < 0.05). The administration of KP102 into the rumen failed to stimulate GH release. The GH response curves (AUC) produced after administration of KP102 into the abomasum or duodenum were 2.2-fold greater than those for after administration into the oral cavity (P < 0.05). The oral administration of 5 mg/kg BW of KP102 in the powder state, not dissolved in 9 ml of saline, failed to stimulate GH release. These results suggested that orally administered KP102 dissolved in saline transiently stimulates GH release in adult goats, and this phenomenon might be due to small amounts of the peptides entering directly into the abomasum with liquid bypassing the rumen.     

Effects of growth hormone-releasing factor on growth hormone response, growth and feed conversion efficiency in buffalo heifers (Bubalus bubalis)

The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers (Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10microg/100kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at -60, -30, 0, +10, +20, +30, +60, +120 and +180min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals. Plasma GH concentrations increased (P=0.001) steadily following bGRF challenge, peaking 10-20min after challenge and declining to baseline by 180min. In the treatment group, there were no significant differences (P>0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations (P<0.01), AGR (P<0.01) and FCE (P=0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers.     

Pituitary adenylate cyclase-activating polypeptide induces secretion of growth hormone in cattle.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hypothalamic neuropeptide that stimulates release of growth hormone (GH) from cultured bovine anterior pituitary gland cells, but the role of PACAP on the regulation of in vivo secretion of GH in cattle is not known. To test the hypothesis that PACAP induces secretion of GH in cattle, meal-fed Holstein steers were injected with incremental doses of PACAP (0, 0.1, 0.3, 1, 3, and 10 microg/kg BW) before feeding and concentrations of GH in serum were quantified. Compared with saline, injection of 3 and 10 microg PACAP/kg BW increased peak concentrations of GH in serum from 11.2 ng/ml to 23.7 and 21.8 ng/ml, respectively (P < 0.01). Peak concentrations of GH in serum were similar in steers injected with 3 or 10 microg PACAP/kg BW. Meal-fed Holstein steers were then injected with 3 microg/PACAP/kg BW either 1 hr before feeding or 1 hr after feeding to determine if PACAP-induced secretion of GH was suppressed after feeding. Feeding suppressed basal concentrations of GH in serum. Injection of PACAP before feeding induced greater peak concentrations of GH in serum (19.2 +/- 2.6 vs. 11.7 +/- 2.6 ng/ml) and area under the response curve (391 +/- 47 vs. 255 +/- 52 ng. ml(-1) min) than injection of PACAP after feeding, suggesting somatotropes become refractory to PACAP after feeding similar to that observed by us and others with growth hormone-releasing hormone (GHRH). We concluded that PACAP induces secretion of GH and could play a role in regulating endogenous secretion of GH in cattle, perhaps in concert with GHRH.     

Effect of long-term administration of human growth hormone-releasing factor and (or) thyrotropin-releasing factor on hormone concentrations in lactating dairy cows

Fifteen cows (87 +/- 8 d in lactation; 641 +/- 33 kg BW) were randomly assigned to treatment and then subjected for 182 d to daily sc injection (1000 hr), in the cervical area, of saline (control), thyrotropin-releasing factor (TRF: 1 micrograms/kg BW), growth hormone-releasing factor (1-29)NH2 (GRF; 10 micrograms/kg BW) or GRF plus TRF (10 and 1 micrograms/kg BW, respectively) according to a 2 x 2 factorial design. On days 1, 31, 88 and 179, jugular blood samples were collected from 2 hr before to 6 hr after injection. Samples were also collected for 5 consecutive days after cessation of treatment. GRF always induced growth hormone (GH) release (600 vs 7925 ng.min/ml) with augmentation of response with time (interaction GRF * day; P less than .001). TRF did not affect (P greater than .25) GH release; there was no interaction (P greater than .25) with time. There was no significant interaction (P greater than .25) between GRF and TRF on GH release. However, the amount of GH release with GRF plus TRF was always greater than with GRF alone (9419 vs 6431 ng.min/ml). TRF induced a significant release of prolactin (23769 vs 42175 ng.min/ml) but GRF reduced the amount of prolactin release on the last day of sampling. TRF induced thyroid stimulating hormone (TSH) release only on the first day of injection while triiodothyronine (T3) and thyroxine (T4) continued to respond to TRF throughout the treatment period. Concentrations of T3 and T4 fell below control levels after cessation of TRF injection. In conclusion, GRF-induced GH release and TRF-induced Prl and thyroid hormone release were maintained over a 6-mo treatment period. TRF induced TSH release only on the first day of injection. Overall, these results raised the possibility of a direct effect of TRF on the thyroid gland.     

Growth hormone-releasing hormone and somatostatin concentrations in the hypophysial portal blood of conscious sheep during the infusion of growth hormone-releasing peptide-6

The effects of growth hormone-releasing peptide-6 (GHRP-6) on peripheral plasma concentrations of growth hormone (GH) and hypophysial portal plasma concentrations of growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) were investigated in conscious ewes. Paired blood samples were collected from the hypophysial portal vessels and from the jugular vein of nine ewes for at least 2 hr. The sheep were then given a bolus injection of 10 μg of GHRP-6 per kg followed by a 2-hr infusion of GHRP-6 (0.1 μ/kg · hr). Blood sampling continued throughout the infusion and for 2 hr afterwards. An increase in plasma GH concentration was observed in the jugular samples of six of the nine ewes (1.4 ± 0.3 vs 7.4 ± 2.0 ng/ml, P < 0.05) 5–10 min after the GHRP-6 bolus injection, but in no case did we observe a significant coincident release of GHRH. During the infusion period, mean plasma GHRH levels were not significantly increased but there was a 50% increase (P < 0.05) in GHRH pulse frequency; GHRH pulse amplitude was not changed. Mean SRIF concentration, pulse frequency, and pulse amplitude were unchanged by GHRP-6 treatment. These data indicate that GHRP-6 causes a small, but significant effect on the pulsatile secretion of GHRH, indicating action at the hypothalamus or higher centers of the brain. The large initial GH secretory response to GHRP-6 injection does not appear to be the result of GHRP-6 action on GHRH or SRIF secretion.     

Effect of human growth hormone-releasing factor and(or) thyrotropin-releasing factor on hormone concentrations in dairy calves

To determine the effect of chronic treatment with human growth hormone-releasing factor (1-29)NH2 (GRF) and(or) thyrotropin-releasing factor (TRF), 20 calves averaging 70.2 kg BW were divided into four groups (n = 5) according to a 2 X 2 factorial design. For 86 d, calves in each group received twice daily s.c. injections of either .9% NaCl, GRF (5 micrograms/kg BW), TRF (1 microgram/kg BW) or GRF (5 micrograms/kg BW) plus TRF (1 microgram/kg BW). On d 87, all calves received a s.c. injection of GRF (5 micrograms/kg BW) plus TRF (1 microgram/kg BW). Blood samples were collected every 20 min for 18 h on d 1, 29, 57 and 85, and for 8 h on d 87. Hormone responses were measured as area under the hormone concentration curve over time. GRF and TRF acted in synergy (P less than .10) on GH release throughout the treatment period. Growth hormone responsiveness to GRF and(or) TRF decreased (P less than .01) with days of treatment, but this decrease was due to aging rather than to chronic treatment, because GH response to GRF plus TRF was similar (P greater than .10) between control and treated calves on d 87. TRF increased prolactin (Prl) concentration until the end of the treatment period (P less than .01). The response of thyroid-stimulating hormone (TSH) to TRF disappeared (P greater than .10) after 1 mo of treatment, whereas the thyroxine (T4) response decreased (P less than .01) throughout the treatment period. GRF did not induce nor did it interact with TRF on TSH and T4 release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of melatonin injected into the third ventricle on growth hormone secretion in Holstein steers

The effects of melatonin (MEL) injection into the third ventricle (3V) on growth hormone (GH) secretion were investigated in conscious Holstein steers. A stainless steel cannula was stereotaxically implanted in the 3V based on the ventriculogram. In Exp. 1, three doses of MEL (100, 300 or 600 microg) were injected into the 3V through the cannula and the GH concentration after the injection was determined. In Exp. 2, intracerebroventricular (icv) and intravenous (iv) injections of MEL (100 microg) and GH-releasing hormone (GHRH; 0.25 microg/kg body weight), respectively, were performed simultaneously to examine the effect of MEL on GHRH-induced GH release. The icv injection of MEL significantly stimulated GH release at 100 microg. The increase in GH concentrations by 100 microg of MEL was persistent. Intravenous injection of GHRH dramatically increased GH release. The injection of MEL did not alter GHRH-induced GH release. These results suggest that MEL stimulates GH secretion possibly through the hypothalamus in cattle.     

Effect of daily injections of growth hormone-releasing factor and thyrotropin-releasing hormone on growth and endocrine parameters in chickens

The control of growth is a complex mechanism regulated by several metabolic hormones including growth hormone (GH) and thyroid hormones. In avian species, as well as in mammals, GH secretion is regulated by hypothalamic hypophysiotropic hormones. Since thyrotropin-releasing hormone (TRH) and growth hormone-releasing factor (GRF) are potent GH secretagogues in poultry, we were interested in determining the influence of daily intravenous administration of either peptide or both simultaneously on circulating GH and IGF-I concentrations and whether an improvement in growth rate or efficiency would be obtained.

Male broiler chicks were injected once daily for a period of 21 days with either GRF (10 μg/kg), TRH (1 μg/kg) or both GRF and TRH (10 and 1 μg/kg respectively) between four and seven weeks of age. On the last day of the experiment, following intravenous injection of TRH, GRF or a combination of GRF and TRH, plasma GH levels were significantly (P<.05) increased to a similar extent in control chicks and in those which had received daily peptide injections for the previous 21 days. Circulating GH levels between 10 and 90 min post-injection were significantly (P<.05) greater and more than additive than GH levels in chicks injected with both GRF and TRH when compared to those injected with either peptide alone. Mean plasma T₃ concentrations during that same time period were significantly elevated (P<.05) above saline-injected control chick levels in birds treated with TRH or GRF and TRH respectively, regardless of whether the chicks had received peptide injections for the previous 21 days. There was no evidence of pituitary refractoriness to chronic administration of either TRH or GRF injection in terms of growth or thyroid hormone secretion.

Despite the large elevation in GH concentration each day, growth rate, feed efficiency and circulating IGF-I concentrations were not enhanced. Thus the quantity or secretory pattern of GH secretion induced by TRH or GRF administration was not sufficient to increase plasma IGF-I concentration or growth.     

Effects of administration of growth hormone-releasing factor to sows during late gestation on growth hormone secretion, reproductive traits, and performance of progeny from birth to 100 kilograms live weight.

The effects of growth hormone-releasing factor (GHRF) injections to sows during late gestation were investigated in two experiments. In the first one, four treatments were applied to eight catheterized sows according to two 4 x 4 Latin squares: oral administration of 2 mg of pyridostigmine, a cholinesterase inhibitor, per kilogram of BW (PYR group); i.m. injection of 50 micrograms of GHRF/kg BW (GHRF group); a combination of the pyridostigmine and GHRF treatments (PYR+GHRF); or i.m. injection of glucose (control). Pyridostigmine slightly increased the plasma concentration of growth hormone (GH). Growth hormone responses to GHRF and PYR+GHRF treatments were similar, with significantly elevated GH concentrations from 5 to 240 min after GHRF injection. In the second experiment, 36 sows were allocated to two treatments at 102 d of gestation. Until farrowing, they were injected twice daily with 50 micrograms of GHRF/kg BW (GHRF group) or isotonic glucose (control). The DM, N, fat, and energy content of 24 pigs per group was determined at weaning at 22 d. Six pigs per litter had ad libitum access to feed until slaughter at 100 kg BW and their carcasses were evaluated. Treatment with GHRF increased pregnancy duration (114.8 vs 113.6 d, P less than .05), weight of pigs at 13 d (3.69 vs 3.54 kg, P less than .05) and at weaning (5.74 vs 5.48 kg, P less than .05), and improved pig survival (86 vs 71%, P less than .05). Lipid (on a DM basis) and energy contents of the pigs slaughtered at weaning were significantly higher in the GHRF group than in the control group (14.4 vs 12.5% and 2,178 vs 2,029 kcal/kg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergism and diurnal variations of human growth hormone-releasing factor (1-29)NH2 and thyrotropin-releasing factor on growth hormone release in dairy calves

Sixteen male Holstein calves averaging 168 kg body weight (BW) were used to determine the effects of human growth hormone-releasing factor (1–29)NH₂ (hGRF (1–29)NH₂; .22 μg/kg BW), thyrotropin-releasing factor (TRF; .165 μg/kg BW) or hGRF (1–29)NH₂ plus TRF (.22 and .165 μg/kg BW, respectively) on growth hormone (GH) release in animals exposed to 16 hr of light (L): 8 hr of dark (D) (lights on at 0100 hr) and hGRF plus TRF (.22 and .165 μg/kg BW, respectively) in animals exposed to 8L:16D (lights on at 0900 hr). For each treatment, times of iv injection were 0400, 1000, 1600 and 2200 hr. In animals exposed to 16L:8D, average GH peaks reached after hGRF (1–29)NH₂ or TRF injections were 49.7 and 32.0 ng/ml while the area under the GH response curve (AUC) were 1247 and 1019 ng/ml^*min, respectively. There was no significant effect of times of injection on GH release following the separate injection of hGRF (1–29)NH₂ or TRF. In animals exposed to 16L:8D, GH peaks and AUC after hGRF plus TRF injections were 226.4, 189.2 and 116.8 ng/ml, and 4340, 3660 and 2415 ng/ml^*min at 0400, 1000 and 1600 hr (lights on), respectively but only 42.3 ng/ml and 1692 ng/ml^*min at 2200 hr (lights off). In animals exposed to 8L:16D, GH levels and AUC after hGRF plus TRF injections reached 177.5 and 180.5 ng/ml, and 2759 and 3704 ng/ml^*min at 1000 and 1600 hr (lights on) but only 84.0 and 72.7 ng/ml, and 1544 and 1501 ng/ml^*min at 0400 and 2200 hr (lights off), respectively. These results demonstrated that hGRF (1–29)NH₂ and TRF can act in synergy to potentiate GH release in dairy calves. This synergistic action occurred only when both peptides were injected during the lighted phase of short and long day photoperiods.     

Determination of effective dosage of GH-releasing factor for blood GH responses in mithun (Bos frontalis)

A study was undertaken to determine the effective dosage of GH-releasing hormone (GRF) required to produce blood GH response in mithun (Bos frontalis), a semi-wild ruminant species. For the purpose, 12 mithuns averaging 11.5 months of age and 146 kg body weight (BW) were randomly assigned to receive GRF (n = 12), administered at 0 (normal saline), 5, 10 and 20 mug per 100 kg BW. Blood samples were collected prior to and after GRF administration at -60, -45, -30, -15, -10, -5, 0 min and 5, 10, 15, 30 and thereafter, at 15-min interval up to 8 h post-GRF were assayed for plasma GH. For all the dosages, the pre-treatment GH concentrations and corresponding area under GH response curve (AUC) were similar (p > 0.05). The post-GRF plasma GH responses to different dosages of GRF viz. 5, 10 and 20 mug per 100 kg BW and corresponding AUCs were higher (p < 0.05) than those recorded in normal saline-treated controls. The GH responses to 10 and 20 mug GRF per 100 kg BW and corresponding AUCs were higher (p < 0.05) than those registered in mithuns administered with 5 mug GRF per 100 kg BW. Interestingly, post-GRF concentration of plasma GH and AUCs were not different for 10 and 20 mug GRF per 100 kg BW dosages. In all animals treated with GRF, a peak of GH was registered within 10 to 20 min post-GRF. Following 5 mug GRF per 100 kg BW, GH concentrations were maintained at higher level for 90 min post-GRF and thereafter became similar to that of controls and it was 435 min for 10 and 20 mug GRF per 100 kg BW dosages. In conclusion, our results suggest that 10 mug GRF per 100 kg BW is the dosage, which can be used for augmentation of mithun production.     

The effect of growth hormone-releasing peptide-2 (KP102) administration on plasma insulin-like growth factor (IGF)-1 and IGF-binding proteins in Holstein steers on different planes of nutrition

This study was conducted to investigate the nutrition-dependent changes in insulin-like growth factor (IGF)-1 and IGF-binding proteins (IGFBPs) with growth hormone releasing peptide-2 (D-Ala-D-betaNal-Ala-Trp-D-Phe-Lys-NH(2); GHRP-2 or KP102) treatment in growing Holstein steers. Eight 13 month-old Holstein steers were grouped on two levels of feed intake (high intake (HI); 2.43% body weight or low intake (LI); 1.22%) and each group was daily injected with KP102 (12.5 microg/kg body weight/day) or saline solution into the jugular vein during 6-day period. The concentration of plasma GH showed an increase after an i.v. bolus injection of KP102 on Day 1 and Day 6 in both the LI and HI groups. Plasma IGF-1 began to increase 10 hr following an i.v. bolus injection of KP102, but this was only observed in the HI group (P < 0.05). Also, the plasma IGF-1 in the HI group with daily injections was significantly greater than the LI group from Day 1 of KP102 administration (P < 0.05). It reached maximum values of 125.1 +/- 7.6 ng/ml after Day 2, and returned to pre-injection levels after Day 4, however, no change in plasma IGF-1 was observed in LI with administration of KP102. During 6 days of treatment, plasma 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 were significantly higher in KP102 treated steers but only in the HI group (P < 0.05). Plasma 34 kDa IGFBP-2 decreased in the HI group and did not show any change following an injection of KP102. In conclusion, the effect of stimulated endogenous GH with KP102 administration increased plasma IGF-1, 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 levels in the HI group of growing Holstein steers, but not in the LI one. Thus, we strongly believe that the plasma IGF-1 and IGFBPs response to KP102 treatment is modulated by the nutritional status of growing Holstein steers and the increased plasma IGF-1 concentration with KP102 treatment may be regulated by plasma 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 in Holstein steers.     

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.     

Stimulation of swine growth by porcine growth hormone

Highly purified porcine growth hormone (pGH; USDA-B1) was administered by im injection (22 micrograms X kg body weight-1 X d-1) to rapidly growing Yorkshire barrows for 30 d. Growth hormone significantly increased growth rate (10%), feed efficiency (4%), cartilage growth and muscle mass. However, pGH did not affect carcass adipose tissue mass. Intramuscular lipid content of the longissimus was increased 50% by pGH administration. Plasma pGH concentration was elevated (7- to 11-fold) for 3 to 5 h post-injection. Chronic administration of pGH depressed pituitary GH content and concentration approximately 45%. No GH antibodies were detected in the plasma of GH-treated swine. Plasma somatomedin-C concentration was increased 55% by GH treatment 3 h post-injection. Plasma glucose and insulin concentrations were both significantly increased in GH-treated swine, suggesting that the animals had developed a state of insulin resistance. Plasma-free fatty acid concentration tended to be higher in GH-treated animals. Treatment of swine with pGH significantly decreased plasma blood urea nitrogen. Assessment of animal health during the trial and postmortem indicated that pGH administration did not have any adverse effects. In summary, treatment of young, rapidly growing swine with pGH stimulated growth performance without affecting animal health or inducing the production of GH antibodies.