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.     

Stimulation of Dopamine D1 Receptors Increases Activity of Periventricular Somatostatin Neurons and Suppresses Concentrations of Growth Hormone

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

Relationship between growth hormone (GH) pulses in the peripheral circulation and GH-releasing hormone and somatostatin profiles in the cerebrospinal fluid of goats

Growth hormone (GH) is secreted in a pulsatile manner, but the underlying mechanisms of GH pulse generation remain to be resolved. In the present study, we investigated the relationship between GH pulses in the peripheral circulation and GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal fluid (CSF) of male goats. The effects of an intracerebroventricular (icv) injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood and CSF samples were collected every 15 min for 8 hr from the jugular vein and third ventricle, respectively. GH pulsatility in the goat was found to consist of distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity. GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity, and most of the descending phase of SRIF pulses were associated with the initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated GHRH release without affecting SRIF release. In addition, NPY suppressed, and galanin and ghrelin induced large GH pulses, although ghrelin was much more effective than galanin. These results suggest that an hourly fall in SRIF is involved in generating intrinsic circhoral rhythm of GH pulsatility. The mechanisms underlying the generation of large GH pulses of 5 hr periodicity remain unknown, while direct action of NPY and/or ghrelin on the pituitary might be involved.     

Analogs of growth hormone-releasing hormone induce release of growth hormone in the bovine

Biological potencies of three 29 amino acid growth hormone-releasing hormone analogs (GHRH[1-29]) were determined in the bovine and compared to synthetic human GHRH (44 amino acids; hGHRH[1-44]NH2) for their ability to increase serum growth hormone (GH) concentrations. Four prepubertal Holstein heifers (179 +/- 10 kg) received hGHRH(1-44)NH2 or analogs (D-Ala2, Nle27, Agm29 GHRH[1-29], [JG-73]; D-N-MeAla2, Nle27, Agm29 GHRH[1-29], [JG-75]; and desamino-Tyr1, D-Ala2, Nle27, Agm29 GHRH[1-29], [JG-77]) at the following doses: 0, 6.25, 25, 100 and 400 micrograms/animal. All treatment-dose combinations were administered to each heifer with at least a 1-d interval between treatments. Sixteen blood samples were collected via jugular cannulas 20 min before and up to 6 h after treatment injection. There was a linear dose-dependent GH release in response to hGHRH(1-44)NH2 and the three analogs. Growth hormone peak amplitudes for the three analogs were similar to those observed after administration of the hGHRH(1-44)NH2 (P greater than .05). However, when total area under the GH response curves for each treatment was averaged over all the doses, JG-73 stimulated greater GH release than hGHRH(1-44)NH2 (P less than .05) Heifers injected with the 400-microgram dose of hGHRH(1-44)NH2 or the three analogs showed a primary release of GH followed by a secondary release 1 h later. At all other doses, only a primary GH release was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of growth hormone-releasing factor-induced release of growth hormone from bovine pituitary cells

Growth hormone (GH)-releasing factor (GRF) at concentrations of 10−¹² through 10−⁷M for 6 hr linearly increased GH release (b₁ = 10.4 ± .3) from bovine anterior pituitary cells in culture. Maximum release of GH (262% above controls) occurred at 10−⁷M GRF. In contrast, GH release-inhibiting factor (SRIF) at 10−¹² through 10−⁵M had no effect on basal concentrations of GH. In a second experiment, as the proportion of SRIF relative to GRF increased. SRIF suppression of GRF-induced GH release from anterior pituitary cells increased. In a third experiment, anterior pituitary cells cultured in media containing fetal calf serum (FCS) were treated with cortisol (0 or 10 ng/ml media) for 24 hr before exposure to 10−¹³ through 10−⁷M GRF. GRF linearly increased GH secretion (b₁ = 7.4 ± .3) and cortisol augmented this response (b₁ = 10.5 ± .6). However, when cells were cultured in media containing dextran-charcoal treated FCS, cortisol did not alter GRF-induced GH release. Our results demonstrate that GH response of bovine anterior pituitary cells to GRF was modulated negatively by SRIF. However, augmentation of GRF-induced GH release by cortisol was evident only when cells were cultured in media supplemented with untreated FCS.     

Effect of propranolol on growth hormone response to GH releasing hormone (GHRH 1-44) in the dog.

The present study was undertaken to examine whether beta-adrenergic blockade with propranolol might influence and make less variable the growth hormone (GH) response to exogenous GH releasing hormone (GHRH) 1-44 in the dog. On four separate occasions eight healthy beagles, one to two years old, randomly received either propranolol (40 micrograms kg-1 intravenously) or an equivalent volume of saline, 30 minutes before either GHRH 1-44 (1 microgram kg-1 intravenously) or vehicle was injected. After propranolol alone, GH secretion did not differ from saline (area under the curve [AUC]: 649.5 +/- 128.3 v 633.2 +/- 87.7 ng min ml-1, respectively). GHRH alone elicited a significant increase in GH secretion (AUC: 1230.5 +/- 210.5 ng min ml-1) with a peak concentration of 16.7 +/- 4.8 ng ml-1. When GHRH was injected after propranolol the mean peak (59.1 +/- 14.7 ng ml-1) and secretory area (AUC: 2631.0 +/- 474.4 ng min ml-1) were greater than those observed after GHRH alone. However, from a clinical point of view propranolol pretreatment does not modify the great individual variability of the GH response to GHRH.     

Effects of Ghrelin on growth hormone secretion from cultured adenohypophysial cells in pigs

To clarify the direct effects of Ghrelin on growth hormone (GH) release from anterior pituitary (AP) cells in pigs, GH-releasing effects of human Ghrelin (hGhrelin) and rat Ghrelin (rGhrelin) on porcine AP cells were compared with GHRH in vitro. The AP cells were obtained from 6-month-old pigs and the cells (2 x 10(5) cells per well) were incubated for 2 h with the peptides after incubating in DMEM for 3 days. hGhrelin and rGhrelin significantly stimulated GH release from the cultured cells at doses of 10(-8) and 10(-7)M (P < 0.05). The rates of increase in GH at 10(-8) and 10(-7)M of hGhrelin were 82.7 and 131.9%, while those with rGhrelin were 43.9 and 79.5%, respectively. GHRH significantly stimulated GH release from the cells at a dose as low as 10(-11)M (P < 0.05), and the response to GHRH was greater than that induced by Ghrelins. In time-course experiments, GHRH continued to increase GH concentrations in media until 120 min after incubation; however, those in media treated with hGhrelin reached a plateau 60 min after incubation, and the maximal value was approximately one third that obtained with GHRH. When hGhrelin (10(-8)M) and GHRH (10(-8)M) were added together, additive effects of both peptides on the release of GH were observed (P < 0.05). Somatostatin (SS, 10(-7)M) significantly blunted GH release induced by hGhrelin (10(-8)M) and GHRH (10(-8)M) (P < 0.05). In the presence of SS, additive effects of hGhrelin and GHRH on the release of GH were observed (P < 0.05). These results show that Ghrelin directly stimulates GH release from anterior pituitary cells in pigs; however, the GH-releasing effect is weaker than that of GHRH in vitro. The present results also show that Ghrelin interacts with GHRH and SS to in the release of GH from porcine adenohypophysial cells.     

LH responses to chicken luteinizing hormone-releasing hormone I and II in laying,incubating, and out of lay turkey hens

An experiment was conducted to assess the relative in vivo and in vitro activities of chicken LH-RH-I and -II in laying, incubating and out-of-lay turkey hens. The highest plasma concentrations of LH were measured in laying turkey hens, whereas hypophyseal concentrations were highest in incubating hens (I) and lowest in the laying hens at the end of the laying period (EL). Hypophyseal and plasma concentrations of LH decreased with aging in laying hens (L) and the greater decrease occurred in the hypophyses. An in vitro hypophyseal acute challenge with 2-min pulses of cLHRH I or II (10⁻⁷ M) using a perifusion technique resulted in an increase in the release of LH in out-of-lay (OL) and incubating (I) hens, but not in laying (L) hens. Although both peptides elicited comparable responses in I hens, cLHRH II was more effective in OL hens. This difference was attributable to a greater amplitude of the response, whose duration was unchanged. Hypophyseal desensitization to a subsequent stimulation was observed in OL hens when the interval between stimulations was 30 min, but this did not occur at 60- or 120-min intervals. In vivo, the injection of cLHRH I or II, at doses of 10⁻⁸ and 10⁻¹⁰M/kg B.W. stimulated increases in the plasma concentrations of LH, which were initiated within 1 min of injection in OL and I hens but from 5 to 20 min postinjection in L hens. The responses were dose-related and greater immediate responses were measured with cLHRH I than with cLHRH II. Also, after the injection of cLHRH II at the 10⁻⁸ M/kg B.W. dose, the shape of the LH response consisted of an initial increase, followed by a more sustained phase during which LH concentrations were either stable (I hens) or continued to increase (L and OL hens) from 20 to 60 min after injection. In contrast, the injection of cLHRH I at doses of 10⁻⁸ or 10⁻¹⁰ M/kg or cLHRH II at a dose of 10⁻¹⁰ M/kg in I and OL hens, produced a peak of LH concentrations in plasma within 5 min and thereafter declined gradually. The difference in the in vivo responses to LHRH I and II could not be attributed to a greater potency of cLHRH II, but to a more prolonged action. In summary, the responses to both forms of chicken LH-RH varies markedly with the stage of the reproductive cycle (L, I, and OL) and differs between the in vivo and in vitro situations. Although cLHRH II may be more active than cLHRH I, controversy still surrounds its precise physiological role.     

Recombinant Porcine Leptin Reduces Feed Intake and Stimulates Growth Hormone Secretion in Swine

Two experiments (EXP) were conducted to test the hypothesis that porcine leptin affects GH, insulin-like growth factor-I (IGF-I), insulin, thyroxine (T₄) secretion, and feed intake. In EXP I, prepuberal gilts received intracerebroventricular (ICV) leptin injections. Blood was collected every 15 min for 4 hr before and 3 hr after ICV injections of 0.9% saline (S; n = 3), 10 μg (n = 4), 50 μg (n = 4), or 100 μg (n = 4) of leptin in S. Pigs were fed each day at 0800 and 1700 hr over a 2-wk period before the EXP. On the day of the EXP, pigs were fed at 0800 hr and blood sampling started at 0900 h. After the last sample was collected, feeders were placed in all pens. Feed intake was monitored at 4, 20, and 44 hr after feed presentation. In EXP II, pituitary cells from prepuberal gilts were studied in primary culture to determine if leptin affects GH secretion at the level of the pituitary. On Day 4 of culture, 10⁵ cells/well were challenged with 10⁻¹², 10⁻¹⁰, 10⁻⁸, or 10⁻⁶ M [Ala¹⁵]-h growth hormone-releasing factor-(1-29)NH₂ (GRF), 10⁻¹⁴, 10⁻¹³, 10⁻¹², 10⁻¹¹, 10⁻¹⁰, 10⁻⁹, 10⁻⁸, 10⁻⁷, or 10⁻⁶ M leptin individually or in combinations with 10⁻⁸ and 10⁻⁶ M GRF. Secreted GH was measured at 4 hr after treatment. In EXP I, before injection, serum GH concentrations were similar. Serum GH concentrations increased (P < 0.01) after injection of 10 μg (21 ± 1 ng/ml), 50 μg (9 ± 1 ng/ml), and 100 μg (13 ± 1 ng/ml) of leptin compared with S (1 ± 2 ng/ml) treated pigs. The GH response to leptin was greater (P < 0.001) in 10 μg than 50 or 100 μg leptin-treated pigs. By 20 hr the 10, 50, and 100 μg doses of leptin reduced feed intake by 53% (P < 0.08), 76%, and 90% (P < 0.05), respectively, compared with S pigs. Serum IGF-I, insulin, T₄, glucose, and free fatty acids were unaffected by leptin treatment. In EXP II, relative to control (31 ± 2 ng/well), 10⁻¹⁰, 10⁻⁸, and 10⁻⁶ M GRF increased (P < 0.01) GH secretion by 131%, 156%, and 170%, respectively. Only 10⁻⁶ M and 10⁻⁷ M leptin increased (P < 0.01) GH secretion. Addition of 10⁻¹¹ and 10⁻⁹ M leptin in combination with 10⁻⁶ M GRF or 10⁻¹¹ M leptin in combination with 10⁻⁸ M GRF-suppressed (P < 0.05) GH secretion. These results indicate that leptin modulates GH secretion and, as shown in other species, leptin suppressed feed intake in the pig.     

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.     

Effects of estrogen on growth hormone pulsatility in peripheral blood and neuropeptide profiles in the cerebrospinal fluid of goats

We previously reported that growth hormone (GH) pulses were negatively associated with neuropeptide Y (NPY) profiles in cerebrospinal fluid (CSF) of the third ventricle of Shiba goats. In addition, while most GH pulses were coincident with GH-releasing hormone (GHRH) pulses, there was no correlation between GH and somatostatin (SRIF) levels. The present study was performed to elucidate the relationship between GH pulses and these neuropeptide levels in CSF when estradiol (1.0 mg/head) was subcutaneously administered to ovariectomized goats. CSF and plasma samples were collected every 15 min for 18 h (from 6 h before to 12 h after injection). GH levels in peripheral blood and GHRH, SRIF and NPY levels in CSF were measured by radioimmunoassay. Pulse/trough characteristics and correlations were assessed by the ULTRA algorithm and cross-correlation analysis. Before estradiol was injected, significant coincidence was found between GHRH pulses and GH pulses, and negative coincidence was found between NPY troughs and GH pulses. Six to 12 h after estradiol injection, the amplitude and area under the curve (AUC) of the GH pulses were markedly increased. The duration and AUC of the GHRH pulses in the CSF were also increased, and stronger synchrony of GHRH with GH was observed. In contrast, the baseline of NPY was significantly decreased, and the negative correlation between the GH pulses and NPY troughs disappeared. The parameters of SRIF troughs were not clearly changed. These observations suggest that estrogen enhances the pattern of secretion of GH in the goat via enhancement of GHRH pulses and decrease of NPY levels.     

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 growth hormone-releasing factor infusion on somatotropin, prolactin, thyroxine, insulin, insulin-like growth factor I and blood metabolites in control and somatostatin-immunized growing pigs.

The aim of this study was to characterize the effects of prolonged infusion of growth hormone-releasing factor (1-29)NH2 (GRF) on plasma concentrations of hormones and metabolites when administered to control pigs and pigs immunized against somatostatin (SRIF). In the first experiment, eight purebred Yorkshire boars averaging 113 +/- 2 kg BW were immunized against SRIF conjugated to bovine serum albumin (BSA) (n = 4) or BSA alone (n = 4). Somatotropin (ST) response to four rates of GRF infusion (0, 1.66, 5 and 15 ng/min/kg BW) for 6 hr was evaluated using a double balanced 4 x 4 Latin square design. During the 4 hr before infusion, SRIF-immunized animals tended (P = 0.06) to have a higher ST release (613 vs 316 ng.min/ml, SE = 232) than controls. During infusion, GRF elicited a dose-dependent increase in ST release in both squares; the ST response was not better in SRIF-immunized animals than in controls (P greater than 0.05) (1435 vs 880 ng.min/ml; SE = 597). In the second experiment, ten purebred Yorkshire boars (5 controls and 5 SRIF-immunized animals) averaging 69 +/- 2 kg BW were continuously infused with GRF at the rate of 15 ng/min/kg BW for six consecutive d. Under GRF infusion, ST concentrations increased (P less than 0.05) from 805 to 4768 ng.min/ml (SE = 507) from day 1 to day 6 in both SRIF-immunized and control animals. Prolactin levels increased (P less than 0.05) with GRF infusion; pattern of increase was different (P less than .01) overtime in control and SRIF-immunized animals. Thyroxine levels increased from 2.53 to 3.45 micrograms/dl (SE = 0.16) after six d of infusion. Insulin-like growth factor I was higher (P less than 0.05) before (139 vs 90 ng/ml; SE = 11) and during (222 vs 185 ng/ml; SE = 11) GRF infusion in SRIF-immunized animals. A transient increase (P less than 0.05) in glucose and insulin was observed in both groups. Immunization against SRIF had no effect on blood metabolites; however, GRF infusion increased free fatty acids from 157 to 204 microEq/l (SE = 11) and decreased blood urea nitrogen from 4.1 to 3.5 mmol/l (SE = 0.2) from day 1 to day 6, respectively. In summary, active immunization against SRIF in growing pigs increased ST and IGF-I concentrations. Infusion of GRF continuously raised ST levels with days of infusion without any sign of decrease responsiveness.     

Effects of active immunization against somatostatin (SRIF) and/or injections of growth hormone-releasing factor (GRF) during gestation on hormonal and metabolic profiles in sows.

The hormonal responses of gestating sows to immunization against somatostatin conjugated to bovine serum albumin (SRIF-IMM) and/or injections of growth hormone-releasing factor (GRF) were studied with thirty-eight second parity sows. Immunization against bovine serum albumin (BSA-IMM) was used as control. First immunizations were done on day 30 and boosters were given on days 44, 58, 72, 86 and 100 of gestation. Injections of GRF (9 mg of GRF (1-29)NH2 per injection) or saline were given at 0800, 1400 and 2000 hr daily from day 90 of gestation until parturition. Mean body weights of sows at 85 and 110 d of gestation were 196.3 and 210.5 kg, respectively (SE = 0.8). Jugular blood samples were collected from 0740 hr to 1100 hr at 20 min intervals on days 90, 101 and 112 of gestation. On day 112, additional samples were collected from 1340 hr to 1700 hr and from 2140 hr to 2300 hr. At 112 d of gestation, antibody titers against SRIF (% binding, 1:150 dilution) were higher (P less than 0.01) for SRIF-IMM (13.5%) vs BSA-IMM (0.95%) sows. There was no effect of SRIF-IMM nor was there a GRF by SRIF-IMM interaction on any variable measured (P greater than 0.05). Injections of GRF increased (P less than 0.01) the area under the curve (AUC) for growth hormone (GH; 305 vs 1623 ng/min/ml). The increase was greater as days of injection increased (P less than 0.05). Administration of GRF did not affect prolactin (Prl) AUC (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

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.     

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.