Influence of age and sex on basal secretion of growth hormone (GH) and on GH-induced release by porcine GH-releasing factor pGRF(1–29NH2) in growing pigs

The aim of this study was to determine the effect of age and sex on basal secretory patterns of growth hormone (GH) and growth hormone-releasing factor (GRF) induced GH release. Eighteen pigs (9 castrated males and 9 females) were stimulated with pGRF(1–29)NH₂ at 7,11,15,19 and 23 weeks of age. Blood samples were taken from each animal via jugular vein cannulate every 20 min, from 6 hr before to 5 hr after iv GRF administration at a dose of 4 μg/kg. GH baseline levels, amplitude of the GH peaks, area under the GH peaks and the overall mean of GH serum levels decreased (P<.001) with age in both sexes. Age also had a marked effect on GRF-induced GH release: the amplitude of GH peaks and area under the GH peaks decreased (P<.001) with age. The GH response to pGRF(1–29)NH₂ varied considerably, depending on the timing of the episodic endogenous secretion of GH. An immediate response (<30 min) was observed when GRF was injected at the end of a trough period or at the beginning of a peak, but there was no immediate response when GRF was injected at the end of a peak or at the beginning of a trough period. Our results show that both endogenous GH secretion and pGRF(1–29)NH₂-induced GH release declines with age, suggesting a decreased sensitivity of the somatotroph cells to GRF with age; and that the high variability of the GH response to pGRF(1–29)NH₂ stimulation depends greatly on the timing of the episodic endogenous GH release, thus implying a possible episodic endogenous somatostatin secretion by the hypothalamus.     

Relationships between the thyroid and somatotropic axes in steers I: Effects of propylthiouracil-induced hypothyroidism on growth hormone, thyroid stimulating hormone and insulin-like growth factor I

The effects of propylthiouracil (PTU)-induced thyroid hormone imbalance on GH, TSH and IGF-I status in cattle were examined. In the first study, four crossbred steers (avg wt 350 kg) were fed a diet dressed with PTU (0, 1, 2 or 4 mg/kg/d BW) in a Latin square design with four 35-d periods. On day 29 in each period, steers were challenged with an intrajugular bolus of thyrotropin releasing hormone (TRH, 1.0 μg/kg). Blood samples were obtained to assess the change in plasma GH and TSH as affected by PTU. Plasma IGF-I was measured from blood samples obtained before and after (every 6 hr for 24 hr) intramuscular injection of bovine GH (0.1 mg/kg, day 31). Doses of 1 and 2 mg/kg PTU increased plasma T₄ (P<.01). At 4 mg/kg, PTU depressed T₄ concentrations to 30% of control (P<.01). Plasma T₃ linearly decreased with increasing doses of PTU (P<.01). Plasma TSH increased when PTU was fed at 4 mg/kg (P<.05) while the TSH response to TRH declined with increasing PTU (P<.02). Neither basal nor TRH-stimulated plasma concentration of GH was affected by PTU; the IGF-I response to GH tended to increase at the 1 and 2 mg/kg PTU (P<.01). In a second study 24 crossbred steers were fed PTU (1.5 mg/kg) for 119 d in a 2 × 2 factorial design with implantation of the steroid growth effector, Synovex-S (200 mg progesterone + 20 mg estradiol), as the other main effect. Basal plasma GH and IGF-I were not affected by PTU treatment. Synovex increased plasma concentration (P<.01) of IGF-I without an effect on plasma GH. The data suggest that mild changes in thyroid status associated with PTU affects regulation of T₃, T₄ and TSH more than GH or IGF-I in steers.     

Response of young broiler chickens to chronic injection of recombinant-derived human insulin-like growth factor-I

The purpose of this study was to determine if exogenous insulin-like growth factor-I (IGF-I) would improve growth rate or body composition of young broiler chickens. Broiler cockerels were given a daily intramuscular (im) injection of sodium acetate buffer (buffer control), 100 or 200 μg recombinant-derived human IGF-I (rhIGF-I) per kg body weight from 11 to 24 days of age. Exogenous IGF-I did not affect the average daily gain, average daily feed consumption, or the gain-to-feed ratio of broiler chickens. Although daily injection of 200 μg/kg of rhIGF-I reduced (P<0.05) body ash content, there was no significant effect of IGF-I treatment on either body fat or protein content. Plasma GH levels were depressed (P<0.05) by chronic treatment with rhIGF-I. In contrast, plasma levels of T₃ and T₄ were not affected by rhIGF-I treatment. The half-life of rhIGF-I in plasma was determined at 25 days of age in naive control or chronically-injected chickens after a single intravenous dose of 50 μg rhIGF-I/kg. We found a single compartment, first-order disappearance pattern of rhIGF-I from chicken plasma. The half-life (t_1/2) of rhIGF-I in plasma was similar (t_1/2 = 32.5 min) for naive controls (injected once) or chronically-treated chickens which had received a daily injection of rhIGF-I (100 or 200 μg/kg) for 14 d. These data indicate that daily injection of IGF-I cannot be used to enhance growth performance or body composition of broiler chickens when given during the early growth period. The depression of plasma GH levels in rhIGF-I-injected chickens supports a negative-feedback role of IGF-I on pituitary GH secretion.     

Effects of chronic GRF treatment on lambs having low or normal birth weight

The effects of a long term treatment with human GRF(1–29)NH2 on plasma growth hormone (GH), somatomedin C (Sm-C), histomorphometric parameters of bone growth and body composition were investigated in normal and low birthweight male lambs. The animals were divided into two groups according to their birthweight: 24 normal birthweight (NBW) lambs weighing more than 4 kg and 22 low birthweight (LBW) lambs weighing less than 2.5 kg at birth. Half of the animals in each group received two daily subcutaneous injections (8 μg/kg body weight) of hGRF(1–29)NH2 (GRF) from birth to slaughter at 45 or 90 days of age. The other animals received the solvant only. At the beginning and at the end of the treatment, plasma GH and serum Sm-C concentrations were measured in all groups. After slaughter, a histomorphometric study was performed on undecalcified sections of metacarpal growth plates, and the remaining of the carcass was pulverized to study the chemical body composition.

GRF induced GH release in both GRF-treated groups. However, plasma GH reached higher (P<.001) concentrations and the GRF-induced GH peak lasted longer in LBW than in NBW lambs. At day 45, the GRF treatment increased (P<.05) serum Sm-C concentrations in LBW. Most of histomorphometric parameters reflecting the metacarpal growth in length, were not statistically modified under GRF treatment. However, the size of degenerative cells was smaller (P<.05) in LBW treated lambs as compared to controls. Consequently, the cell production in the growth plate was increased (P<.05) under GRF treatment. In both NBW and LBW groups at 45 days of treatment, GRF treatment reduced the amounts of lipids (P<.025) and energy (P<.05), while increased (P<.01) phosphorus deposition in the body. In contrast, there was no effect of GRF treatment on protein content.

We conclude from this experiment that the induction of GH secretion by a chronic treatment with GRF is able to modify some patterns of growth. However, most of the effects of GRF were observed in LBW lambs and after 45 days of treatment only. This suggests that treatment with GRF may serve to compensate for growth in growth-retarded animals. Further studies with different mode of GRF administration should indicate whether it is as much effective in normal animals.     

Relationship of thyroid status to growth hormone and insulin-like growth factor-I (IGF-I) in plasma and IGF-I mRNA in liver and skeletal muscle of cattle

Steers were made hyperthyroid or hypothyroid to study the effects of physiological alterations in thyroid hormone status on plasma growth hormone (GH) profiles, plasma insulin-like growth factor-I (IGF-I) concentrations, and relative abundance of IGF-I mRNA in skeletal muscle and liver. Eighteen yearling crossbred steers (360 to 420 kg) were randomly allotted to hyperthyroid (subcutaneous injection 0.6 μg/kg BW L-thyroxine for 10 d), hypothyroid (oral thiouracil; 0.25% diet plus 12.5 g capsule/d for 17 d), or control (subcutaneous injection 0.9% NaCl) treatment groups. Blood samples were taken for measurement of GH, IGF-I, thyroxine (T₄) and triiodothyronine (T₃) by RIA. Samples of liver and skeletal muscle were taken by biopsy for measurement of IGF-I mRNA by solution hybridization. Steers receiving thiouracil had 57 and 53% (P<.05) lower T₄ and T₃, respectively, than control steers (84.1 and 1.7 ng/ml). The hyperthyroid steers had 228 and 65% greater (P<.05) T₄ and T₃ than control steers. Neither increased nor decreased thyroid status had any significant effects on plasma GH profiles, liver IGF-I mRNA, or plasma concentration of IGF-I. There was no effect of thyroid hormone alteration on skeletal muscle IGF-I mRNA concentrations. The results of this study suggest that short-term changes in thyroid status of cattle had no major impact on the GH-IGF-I axis or skeletal muscle IGF-I mRNA.     

Effect of exogenous thyrotropin-releasing hormone (TRH) administration on plasma levels of triiodothyronine (T3), thyroxine (T4) and growth hormone (GH) in chronically catheterized suckling piglets.

The purpose of the present study was to determine experimental conditions to stimulate secretion of thyroid hormones (T₃ and T₄) with thyrotropin-releasing hormone (TRH) injections in suckling piglets during the first weeks of postnatal life. Three consecutive experiments were conducted. Four 10–20 d old piglets were i.m. injected with 0, 20, 100, 500 μg (experiment 1) or 0, 4, 20, 100 μg TRH/kg BW (experiment 2) according to a 4 × 4 latin square design involving different litters in each experiment. Blood samples were taken −15, −1, 15, 30, 45, 60, 90, 120 180 and 300 min after TRH injection in experiment 1, and −.25, −.08, .25, .5, 1, 2, 4, 6, 8, 12, 24, 30, 36, 48, 60 and 72 hr after TRH injection in experiment 2. T₃ and T₄ levels were significantly (P<.01) increased as soon as 30 and 45 min after TRH injection, respectively. Maximal levels of T₃ and T₄ were obtained 2 and 4 hr after the injection of 100 μg TRH. T₃ and T₄ returned to basal levels within 6 and 8 hr post injection, respectively. Plasma pGH levels were significantly (P<.001) increased 15 min after TRH injection in piglets injected with 500 μg. In experiment 3, 100 μg TRH/kg BW were injected i.m. either daily or every other day from .0 to 23 days of age. Results showed that T₄ response to TRH did not decrease after repeated injections. These results indicate that daily i.m. injections of 100 μg TRH/kg BW can be used to increase thyroid hormone levels for at least 13 d in the young suckling piglet.     

Dose effect of human growth hormone-releasing factor and thyrotropin-releasing factor on hormone concentrations in lactating dairy cows

Two experiments were conducted to study the effects of growth hormone-releasing factor (GRF) and thyrotropin-releasing factor (TRF) administration on hormone concentrations in dairy cows. In the first trial, 12 cows were used on 5 consecutive days to determine the effect of four sc doses of GRF (0, 1.1, 3.3 and 10 μg•kg⁻¹ BW) and three sc doses of TRF (0, 1.1 and 3.3 μg•kg⁻¹ BW) combined in a factorial arrangement. GRF and TRF acted in synergy (P = .02) on serum growth hormone (GH) concentration even at the lowest dose tested and GH response to the two releasing factors was higher than the maximal response observed with each factor alone. TRF increased (P<.01) prolactin (Prl), thyrotropin (TSH), triiodothyronine (T₃) and thyroxine (T₄) concentrations similarly at the 1.1 and 3.3 μg•kg⁻¹ doses and GRF did not interact (P>.40) with TRF on the release of these hormones. In the second trial, the effect of GRF (3.3 μg•kg⁻¹ BW, sc) and TRF (1.1 μg•kg⁻¹ BW, sc) was tested at three stages (18, 72 and 210 days) of lactation on serum Prl and TSH concentrations. Eighteen cows (n = 6 per stage of lactation) were used in two replicates of a 3 × 3 latin square. The TRF and GRF-TRF treatments were equipotent (P>.05) in increasing Prl and TSH concentrations. Prl and TSH responses were similar (P>.40) throughout lactation. In summary, GRF at doses ranging from 1.1 to 10.0 μg•kg⁻¹ and TRF at doses ranging from 1.1 to 3.3 μg•kg⁻¹ act in synergy on GH release and do not interact on Prl, TSH, T₃ and T₄ concentrations in dairy cows. Furthermore, Prl and TSH response to TRF are not affected by stage of lactation.     

Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net hormone metabolism by portal-drained viscera and liver.

Effects of growth hormone-releasing factor (GRF) and intake on arterial concentrations and net visceral metabolism of hormones were measured in six growing Hereford x Angus steers using a split-plot design with 4-wk injection periods within 8-wk intake periods. Steers were fed a 75% concentrate diet at two intakes and were injected s.c. twice daily with saline or GRF (10 micrograms/kg of BW). Arterial concentrations of growth hormone (GH) were measured on d 1 and d 8 to 10 of injections. Eleven measurements, obtained at 30-min intervals, of arterial concentration and net flux of hormones across portal-drained viscera (PDV) and liver were obtained on d 8 to 10 of injections (six hourly measurements were used for insulin-like growth factor-I [IGF-I] and somatostatin). The area under the GH curve and average and peak GH concentrations were increased (P less than .01) by GRF and were greater (P less than .10) at low than at high intake. Liver removal of GH was not affected by GRF or intake. Arterial IGF-I concentration was increased (P less than .05) by GRF and not affected by intake. Treatments did not affect IGF-I flux across the liver. Arterial insulin concentration was greater (P less than .05) at high than at low intake, in part because of greater (P less than .01) PDV release. Increased (P less than .10) arterial insulin concentration in GRF-treated steers was not attributable to significant changes in PDV or liver net flux. Arterial glucagon concentration was greater (P less than .01) at high than at low intake, in part because of greater (P less than .05) PDV glucagon release and decreased (P less than .10) liver extraction ratio. Effects of intake on arterial concentration of insulin and glucagon were in part due to changes in visceral metabolism, but GRF did not affect PDV or liver hormone metabolism.     

Effects of VIP and GRF on the release of growth hormone in perifused bovine adenohypophysis

The effects of vasoactive intestinal polypeptide (VIP) and growth hormone releasing factor (GRF:hpGRF(1–29)-NH₂) on the release of growth hormone (GH) from anterior pituitaries from cows were examined by using an in vitro superfusion system. The pituitaries were excised randomly from cycling cows, dissected to obtain medial portions, and minced to obtain cubes with approximate dimensions of 1.5mm on a side. For each perifusion setup, 5 pieces of pituitary tissues were chambered and flushed with modified KRB solution saturated with 95% O₂-5% CO₂ at 38C. Perifusion with media containing 10⁻⁶ and 10⁻⁷M VIP for 30 min induced a significant release of GH during the treatments (P<0.05). VIP (10⁻⁸M) increased GH levels significantly (P<0.05), but to a minor degree. Perifusion with the media containing 10⁻⁶, 10⁻⁷ and 10⁻⁸M GRF for 30 min markedly increased the GH concentration and the effects continued up to 90 min after termination of the perifusion of the peptide (P<0.05, P<0.01). The GH releasing effects of GRF could be seen at doses as low as 10⁻¹¹M GRF (P<0.05, P<0.01).

These findings indicate that the GH releasing effect of VIP is less potent that that of GRF in cows.     

Effects of cimaterol administration on plasma concentrations of various hormones and metabolites in friesian steers

The aim of the experiment was to determine the acute and chronic effects of the β-agonist, cimaterol, on plasma hormone and metabolite concentrations in steers. Twelve Friesian steers (liveweight = 488 ± 3 kg) were randomly assigned to receive either 0 (control; n=6) or .09 mg cimaterol/kg body weight/day (treated; n=6). Steers were fed grass silage ad libitum. Cimaterol, dissolved in 140 ml of acidified distilled water (pH 4.2), was administered orally at 1400 hr each d. After 13 d of treatment with cimaterol or vehicle (days 1 to 13), all animals were treated with vehicle for a further 7 d (days 14 to 20). On days 1, 13 and 20, blood samples were collected at 20 min-intervals for 4 hr before and 8 hr after cimaterol or vehicle dosing. All samples were assayed for growth hormone (GH) and insulin, while samples taken at −4, −2, 0, +2, +4, +6 and +8 hr relative to dosing were assayed for thyroxine (T₄), triiodothyronine (T₃), cortisol, urea, glucose and non-esterified fatty acids (NEFA). Samples taken at −3 and +3 hr relative to dosing were assayed for IGF-I only. On day 1, cimaterol acutely reduced (P<.05) GH and urea concentrations (7.6 vs 2.9 ± 1.4 ng/ml; and 6.0 vs 4.9 ± 0.45 mmol/l, respectively; mean control vs mean treated ± pooled standard error of difference), and increased (P<.05) NEFA, glucose and insulin concentrations (160 vs 276 ± 22 μmol/l, 4.1 vs 6.2 ± 0.15 mmol/l and 29.9 vs 179.7 ± 13.9 μU/ml, respectively). Plasma IGF-I, T₃, T₄ and cortisol concentrations were not altered by treatment. On day 13, cimaterol increased (P<.05) GH and NEFA concentrations (7.7 vs 14.5 ± 1.4 ng/ml and 202 vs 310 ± 22 mEq/l, respectively) and reduced (P<.05) plasma IGF-I concentrations (1296 vs 776 ± 227 ng/ml). Seven-d withdrawal of cimaterol (day 20) returned hormone and metabolite concentrations to control values. It is concluded that : 1) cimaterol acutely increased insulin, glucose and NEFA and decreased GH and urea concentrations, 2) cimaterol chronically increased GH and NEFA and decreased IGF-I concentrations, and 3) there was no residual effect of cimaterol following a 7-d withdrawal period.     

Concentrations of insulin-like growth factor I and steroids in follicular fluid of preovulatory bovine ovarian follicles: effect of daily injections of a growth hormone-releasing factor analog and(or) thyrotropin-releasing hormone

To determine whether long-term administration of growth hormone (GH)-releasing factor (GRF) and(or) thyrotropin-releasing hormone (TRH) alters ovarian follicular fluid (FFL) concentrations of insulin-like growth factor-I (IGF-I), progesterone, and estradiol (E2), and follicular growth, Friesian x Hereford heifers (n = 47; 346 +/- 3 kg) were divided into the following four groups: control (vehicle; n = 11); 1 micrograms GRF (human [Des NH2 Tyr1, D-Ala2, Ala15] GRF [1-29]-NH2).kg-1 BW.d-1 (n = 12); 1 microgram TRH.kg-1 BW.d-1 (n = 12); or GRF + TRH (n = 12). Daily injections (s.c.) continued for 86 d. On d 89, heifers that had been synchronized were slaughtered and ovaries were removed. Follicles were grouped by magnitude of diameter into the three following sizes: 1 to 3.9 mm (small, n = 55), 4.0 to 7.9 mm (medium, n = 63), and greater than or equal to 8 mm (large, n = 71). Growth hormone-releasing factor and(or) TRH did not affect (P greater than .10) IGF-I concentrations in FFL of any follicle size group. Growth hormone-releasing factor increased (P less than .06) size (means +/- pooled SE) of large follicles (14.7 vs 13.0 +/- .6 mm). Growth hormone-releasing factor also increased (P less than .05) progesterone concentrations 4.4-fold above controls in FFL of medium-sized follicles but had no effect on progesterone in FFL of the small or large follicles. Thyrotropin-releasing hormone did not alter FFL progesterone or E2 concentrations in any follicle size group. We conclude that the GRF and(or) TRH treatments we employed did not affect intra-ovarian IGF-I concentrations, but GRF may alter steroidogenesis of medium-sized follicles and growth of large follicles.     

The release of growth hormone (GH): relation to the thyrotropic- and corticotropic axis in the chicken

In the chicken and other avian species, the secretion of GH is under a dual stimulatory and inhibitory control of hypothalamic hypophysiotropic factors. Additionally, the thyrotropin-releasing hormone (TRH), contrary to the mammalian situation, is also somatotropic and equally important in releasing GH in chick embryos and juvenile chicks compared to the (mammalian) growth hormone-releasing hormone (GHRH) itself. Consequently, the negative feedback loop for GH release not only involves the insulin-like growth factor IGF-I but also thyroid hormones. In adult chickens, TRH does no longer have a clear thyrotropic activity, whereas its somatotropic activity depends on the feeding status of the animal. In addition, as in mammals, the secretion of GH and glucocorticoids is stimulated by ghrelin, a novel peptide predominantly synthesized in the gastrointestinal tract. Two chicken isoforms of the ghrelin receptor have been identified, both of which are highly expressed in the hypothalamus and pituitary, suggesting that a stimulatory effect may be directed at these levels. GH and glucocorticoids control the peripheral thyroid hormone function by down-regulating the hepatic type III deiodinating enzyme (D3) in embryos (GH and glucocorticoids) and in juvenile and adult chickens (GH). Moreover, glucocorticoids help to regulate T3-homeostasis in the brain during embryogenesis by stimulating the type II deiodinase (D2) expression. This way not only a multifactorial release mechanism exists for GH but also a functional entanglement of activities between the somatotropic-, thyrotropic- and corticotropic axis.     

Neuroendocrine regulation of growth hormone secretion in sheep. IV. Central and peripheral cholecystokinin

The result of alterations in the levels of CCK, in the blood and in the cerebrospinal fluid, on the functioning of the growth hormone axis has been examined in sheep. Male Coopworth sheep of about 40 kg liveweight were given various doses of CCK either intracerebroventricularly (icv) or intravenously (iv). Other similar sheep were given various doses of a CCK antagonist (loxiglumide) by the same routes. Bolus iv administration of either 35 μg or 200 μg of CCK had no effect on plasma GH levels. When given icv, however, CCK resulted in a marked (P<0.01) prolonged depression in plasma GH levels. The decrease in GH secretion could be partially attenuated by concurrent administration of loxiglumide, but was completely unaffected by concurrent administration of anti-somatostatin serum icv. Loxiglumide alone had no effect on plasma GH levels when given at up to 200 μg icv, but intravenous administration of 8 mg of the CCK antagonist resulted in an increase in plasma GH concentrations (P<0.05). Plasma levels of somatostatin, glucose and cortisol were unaffected by both icv and iv administration of CCK. These results show that CCK can have a strong GH-inhibiting effect in the brain. Furthermore, this effect seems to be independent of hypothalamic somatostatin, suggesting another GH-inhibiting system exists.     

Effects of pituitary adenylate cyclase-activating polypeptide (PACAP), prostaglandin E2 (PGE2) and growth hormone releasing factor (GRF) on the release of growth hormone from cultured bovine anterior pituitary cells in vitro

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on growth hormone (GH) release was compared with that of prostaglandin E₂ (PGE₂) and growth hormone releasing factor (GRF) from cultured bovine anterior pituitary cells in vitro. Both PACAP and PGE₂ stimulated GH release at concentrations as low as 10⁻⁹ and 10⁻⁸ M, respectively, (P<0.01). However, GRF released GH at a concentration as low as 10⁻¹³ M (P<0.01). Percent increases of GH compared with controls were not significantly different among GRF, PACAP, and PGE₂ at 10⁻⁷ M; however, the increases of GH by the 10⁻⁸ M GRF, PACAP and PGE₂ were 196, 118, and 27%, respectively, (P<0.01), and 124, 65, and 1% in the 10⁻⁹ M media, respectively, (P<0.01). When GRF and somatostatin (SS) were added together, the GH releasing effect of GRF was blunted (P<0.01). Similar bluntness were observed in PACAP and PGE₂, when SS was added. The stimulatory effects of GRF and PGE₂ together were similar to that by either GRF or PGE₂ alone. When GRF and PACAP were added together, the GH released by both secretagogues was greater than that by PACAP alone (P<0.01); however, a synergistic effect was not clear when compared with GRF alone.

These findings suggest that PACAP and PGE₂ may modulate the release of GH in cattle.     

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.     

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.     

Effects of somatostatin immunoneutralization on growth and endocrine parameters in chickens

The effects of somatostatin immunoneutralization on growth rate, growth hormone (GH) secretion and circulating insulin-like growth factor I (IGF-I) concentrations were investigated in chickens through the use of passive and active immunization techniques. Intravenous bolus injection of goat-antisomatostatin stimulated a significant (P less than .05) increase in plasma GH levels for one hour post-injection in four and six week old male broiler chickens. The GH response to an intravenous bolus injection of hGRF44NH2 was similar in the antisomatostatin treated chicks and normal goat serum treated controls. Despite the presence of circulating somatostatin antisera after 28 hours, plasma GH levels were not different between control and antisomatostatin-treated chicks at that time. Continuous administration of somatostatin antisera by Alzet pump over a two-week period resulted in significant (P less than .05) elevations in plasma GH levels at one week post-implantation and in circulating IGF-I concentrations after two weeks of administration. Chicks which developed antibodies against somatostatin following active immunization exhibited a 7.1% increase in growth rate which was associated with a significant decrease in abdominal fat. However, neither GH nor IGF-I concentrations were elevated in the chicks which developed somatostatin antibodies. Thus, the benefits gained from somatostatin immunoneutralization may be exerted through mechanisms other than GH.     

Effect of long-term administration of porcine growth hormone-releasing factor and(or) thyrotropin-releasing factor on growth hormone, prolactin and thyroxine concentrations in growing pigs

Long-term administration of porcine growth hormone-releasing factor (pGRF(1-29)NH2) and(or) thyrotropin-releasing factor (TRF) was evaluated on serum concentrations of growth hormone (GH) thyroxine (T4) and prolactin (PRL). Twenty-four 12-wk-old female Yorkshire-Landrace pigs were injected at 1000 and 1600 for 12 wk with either saline, pGRF (15 micrograms/kg), TRF (6 micrograms/kg) or pGRF + TRF using a 2 x 2 factorial design. Blood samples were collected on d 1, 29, 57 and 85 of treatment from 0400 to 2200. Areas under the GH, T4 and PRL curves (AUC) for the 6 h (0400 to 1000) prior to injection were subtracted from the postinjection periods (1000 to 1600, 1600 to 2200) to calculate the net hormonal response. The AUC of GH for the first 6 h decreased similarly (P less than .05) with age for all treatments. The GH response to GRF remained unchanged (P greater than .10) across age. TRF alone did not stimulate (P less than .05) GH release but acted in synergy with GRF to increase (P less than .05) GH release. TRF stimulated (P less than .001) the net response of T4 on all sampling days. Animals treated with the combination of GRF + TRF showed a decreased T4 AUC during the first 6 h on the last three sampling days. Basal PRL decreased (P less than .05) with age. Over the four sampling days, animals injected with TRF alone showed (P less than .01) a reduction (linear effect; P less than .01) followed by an increase (quadratic effect; P less than .05) in total PRL concentration after injection; however, when GRF was combined with TRF, such effects were not observed (P greater than .10). Results showed that 1) chronic injections of GRF for 12 wk sustained GH concentration, 2) TRF and GRF acted synergistically to elevate GH AUC, 3) TRF increased T4 concentrations throughout the 12-wk treatment period, 4) chronic TRF treatment decreased the basal PRL concentration and 5) chronic GRF + TRF treatment decreased the basal concentration of T4.     

Potent interaction between thyrotropin releasing hormone (TRH) and human pancreatic growth hormone releasing factor (hpGRF) in stimulating chicken growth hormone (cGH) in vivo: Hypothalamic noradrenergic mediation in TRH stimulation of cGH release

The interaction of human pancreatic growth hormone releasing factor (hpGRF) and thyrotropin releasing hormone (TRH) on chicken growth hormone (cGH) release in vivo and possible noradrenergic involvement on TRH-induced stimulation of cGH in vivo were examined. Four-week old cockerels (1 kg) were injected intravenously with hpGRF (1.0 μg/bird), TRH (0.1 μg/bird), or hpGRF (1.0 μg/bird) in combination with TRH (0.1 μg/bird). Five min after the injection, blood samples were collected and serum concentrations of cGH were determined by a homologous RIA. The results showed that hpGRF and TRH were potent stimulators of cGH release, 5- and 6-fold over the control birds, respectively, and that hpGRF and TRH administered in combination produced a synergistic stimulation of cGH release (>20 fold). In separate experiments, pretreatment with alpha-methyl-para-tyrosine (250 mg/bird) for 2 hours resulted in complete suppression of the TRH stimulatory effect on cGH release but not the stimulatory effect of hpGRF. Pretreated with phenoxybenzamine hydrochloride (20 mg/bird) or diethyl-dithiocarbamate (500 mg/bird) also resulted in complete suppression of TRH-induced cGH release. These results indicate that hpGRF acts directly at the pituitary and TRH acts at the hypothalamus in addition to the pituitary in stimulating cGH release, possibly mediated through the noradrenergic neurons. HpGRF and TRH were potent releasers of cGH and their stimulation was potentiated when administered together.     

Stimulated growth hormone release in juvenile cattle genetically selected for high and low milk yield

The purpose of the present study was to test if plasma growth hormone (GH) concentrations in juvenile male and female cattle before or after intravenous stimulation with secretagogues was affected by selection for high (H) vs. low (L) milk yield in lines of Norwegian cattle. In the first of two experiments (A), 32 yearling heifers (16 H and 16 L, at 307–424 days of age) were tested by use of four doses of growth hormone releasing factor (GRF); 0.02, 0.10, 0.50 and 2.50 μg/kg live weight, on 4 consecutive days. The animals were fed ad libitum on a silage-based ration before and during the experiment. Growth hormone was assayed in plasma from blood samples taken at ?15, ?5, 0, 5, 10, 15, 20, 30, 45 and 60 min from stimulation. Plasma GH concentrations were log transformed before statistical analyses. Response variables were; PRIOR (mean of ?15, ?5 and 0 min samples) and PEAK (mean of 10, 15 and 20-min samples). In experiment B, 37 calves (19 H+18 L, 22 males and 15 females, age 114–259 days) were subjected daily to one of three intravenous stimulation tests (GRF, 0.10 and 0.50 μg/kg or thyrotrophin releasing hormone (TRH) at 0.20 μg/kg live weight) on each of 3 consecutive days. Feeding was restricted to cover estimated maintenance requirements only. Rations were given once daily during the test days and 3 days prior to first test. Blood sampling and variables followed those of experiment A. Selection line did not significantly affect GH variables in experiments A or B at any dose of GRF or TRH. GH response increased with increasing dose of GRF up to 0.50 μg/kg. At the highest GRF dose, the response was delayed and persisted longer. Doses giving intermediate to large response increased repeatability of GH measurements. It is concluded that GH secretion in juvenile cattle can be accurately assessed using GRF based stimulation tests combined with restricted and controlled feeding, but it is not affected by selection for milk yield in Norwegian cattle.