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.     

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.     

Relationship between growth and plasma concentrations of ghrelin and growth hormone in juvenile beagle dogs

Although the release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus, ghrelin also may be involved in GH release during juvenile period. We have examined plasma concentrations of acylated ghrelin, desacyl ghrelin, and GH in juvenile beagle dogs. Plasma acylated and desacyl ghrelin levels changed through aging; however, there was no closely correlation between ghrelin, body weight and circulating GH levels during juvenile period. The increase in body weight was essentially linear until 8 months of age, whereas plasma GH concentrations exhibited bimodal peaks for the meanwhile. The results suggest that ghrelin may not play internal cueing in GH secretion in juvenile beagle dogs.     

The control of adenohypophysial hormone secretion by amino acids and peptides in swine

Several different amino acids and peptides control secretion of adenohypophysial hormones and this control may be indirect, via the modulation of hypothalamic hormone secretion. Indeed, classical hypothalamic hormones (e.g., gonadotropin-releasing hormone [GnRH], growth hormone-releasing hormone [GHRH], somatostatin, etc.) may be released into the hypothalamo-hypophysial portal vasculature, travel to the adenohypophysis and there stimulate or inhibit secretion of hormones. Alternatively, some amino acids and peptides exert direct stimulatory or inhibitory effects on the adenohypophysis, thereby impacting hormone secretion. In swine, the most extensively studied modulators of adenohypophysial hormone secretion are the excitatory amino acids (ExAA), namely glutamate and aspartate, and the endogenous opioid peptides (EOP). In general, excitatory amino acids stimulate release of luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). Secretion of adenohypophysial hormones induced by ExAA is primarily, but perhaps not exclusively, a consequence of action at the central nervous system. By acting primarily at the level of the central nervous system, EOP inhibit LH secretion, stimulate GH release and depending on the animal model studied, exert either stimulatory or inhibitory influences on PRL secretion. However, the EOP also inhibited LH release by direct action on the adenohypophysis. More recently, peptides such as neuropeptide-Y (NPY), orexin-B, ghrelin, galanin, and substance P have been evaluated for possible roles in controlling adenohypophysial hormone secretion in swine. For example, NPY, orexin-B, and ghrelin increased basal GH secretion and modulated the GH response to GHRH, at least in part, by direct action on the adenohypophysis. Secretion of LH was stimulated by orexin-B, galanin, and substance P from porcine pituitary cells in vitro. Because the ExAA and various peptides modulate secretion of adenohypophysial hormones, these compounds may play an important role in regulating swine growth and reproduction.     

Physiology of ghrelin and related peptides

Growth hormone (GH) released from pituitary under direct control of hypothalamic releasing (i.e., GHRH) and inhibiting (i.e., sst or SRIF) hormones is an anabolic hormone that regulates metabolism of proteins, fats, sugars and minerals in mammals. Cyril Bowers' discovery of GH-releasing peptide (GHRP-6) was followed by a search for synthetic peptide and nonpeptide GH-secretagogues (GHSs) that stimulate GH release, as well as a receptor(s) unique from GHRH receptor. GHRH and GHSs operate through distinct G protein-coupled receptors to release GH. Signal transduction pathways activated by GHS increase intracellular Ca2+ concentration in somatotrophs, whereas GHRH increases cAMP. Isolation and characterization of ghrelin, the natural ligand for GHS receptor, has opened a new era of understanding to physiology of anabolism, feeding behavior, and nutritional homeostasis for GH secretion and gastrointestinal motility through gut-brain interactions. Other peptide hormones (i.e., motilin, TRH, PACAP, GnRH, leptin, FMRF amide, galanin, NPY, NPW) from gut, brain and other tissues also play a role in modulating GH secretion in livestock and lower vertebrate species. Physiological processes, such as neurotransmission, and secretion of hormones or enzymes, require fusion of secretory vesicles at the cell plasma membrane and expulsion of vesicular contents. This process for GH release from porcine somatotrophs was revealed by atomic force microscopy (AFM), transmission electron microscopy (TEM) and immunohistochemical distribution of the cells in pituitary during stages of development.     

GH secretory responses to ghrelin and GHRH in growing and lactating dairy cattle

Release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus. A novel peripheral release-regulating hormone, ghrelin, was recently identified. In this study, differences of the GH secretory response to ghrelin and GHRH in growing and lactating dairy cattle were investigated and an alteration of plasma ghrelin levels was observed. The same amounts of ghrelin and GHRH (0.3 nmol/kg) were intravenously injected to suckling and weanling calves, early and mid-lactating cows and non-lactating cows. Plasma ghrelin levels were also determined in dairy cattle in various physiological conditions. The peak values of ghrelin-induced GH secretion were increased in early lactating cows compared to those in non-lactating cows. The relative responsiveness of GH secretion to ghrelin was also increased compared with that to GHRH in early lactating cows. GH secretory responses to GHRH were blunted in mature cows with and without lactation. Conversely, GHRH-induced GH secretory response was greater than that to ghrelin in calves, and also greater in calves than in mature cows. Plasma ghrelin concentrations were elevated in early lactating cows compared to those in non-lactating cows. Plasma GH concentrations were higher in suckling calves and early lactating cows compared with those in non-lactating cows. These results suggest that GHRH is an effective inducer of GH release in growing calves, and that the relative importance of ghrelin in contributing to the rise in plasma GH increases in early lactating cows.     

Correlation between spontaneous feeding behavior and neuropeptide Y profile in the third ventricular cerebrospinal fluid of goats

Feeding behavior is regulated by neural signals in the hypothalamus, but secretory activities of these signals in vivo and their relationship with spontaneous feeding remain to be solved. In the present study, we investigated the correlation between neuropeptide Y (NPY) and somatostatin (SRIF) profiles in cerebrospinal fluid (CSF) and spontaneous feeding behavior in goats. CSF samples were collected every 15 min for 8 h from the third ventricle and feeding behavior was observed throughout the experimental period. The spontaneous feeding behavior, the mean duration of which was 58 min, occurred with an interval of 146 min. NPY in the CSF fluctuated in an episodic fashion with a 145 min interval. Each NPY episode was followed by spontaneous feeding with a time lag of 24 min. SRIF levels in CSF changed more frequently in a pulsatile manner and were related to neither NPY profiles nor feeding behavior. These results suggest that NPY, but not SRIF, is a physiological signal to drive feeding in goats.     

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

The effects of three growth hormone secretagogues (GHSs), ghrelin, growth hormone-releasing peptide-6 (GHRP-6), and growth hormone-releasing hormone (GHRH), on the release of adenohypophyseal hormones, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinising hormone (LH), prolactin (PRL) and on cortisol were investigated in young and old healthy Beagle dogs. Ghrelin proved to be the most potent GHS in young dogs, whereas in old dogs GHRH administration was associated with the highest plasma GH concentrations. The mean plasma GH response after administration of ghrelin was significantly lower in the old dogs compared with the young dogs. The mean plasma GH concentration after GHRH and GHRP-6 administration was lower in the old dogs compared with the young dogs, but this difference did not reach statistical significance. In both age groups, the GHSs were specific for GH release as they did not cause significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH, and PRL. It is concluded that in young dogs, ghrelin is a more powerful stimulator of GH release than either GHRH or GHRP-6. Ageing is associated with a decrease in GH-releasing capacity of ghrelin, whereas this decline is considerably lower for GHRH or GHRP-6.     

Dynamics of GHRH in third-ventricle cerebrospinal fluid of cattle: Relationship with serum concentrations of GH and responses to appetite-regulating peptides

Objectives were to (1) characterize the relationship of third-ventricle (IIIV) cerebrospinal fluid (CSF) concentrations of growth hormone–releasing hormone (GHRH) with concentrations of GH in the peripheral circulation; and (2) assess the influence of acute administration of appetite-regulating peptides leptin (anti-orexigenic) and neuropeptide Y (NPY; orexigenic) on the release of GHRH. Six mature beef cows fitted with IIIV and jugular vein cannulae were treated intracerebroventricularly with saline, and leptin (600 μg) and NPY (500 μg) in saline, in a replicated 3 × 3 Latin square design. Third-ventricle CSF and blood were collected 10 min before and continued 220 min after treatments. Mean concentrations of GHRH and frequency of pulses after treatments were 2.2 ± 0.13 ng/mL and 1.2 ± 0.15 pulses/220 min, respectively. These measures were not influenced by treatments. Concentrations of GHRH in CSF were weakly correlated (r = 0.15; P < 0.03) with serum concentrations of GH; however, 58% of the GH pulses were preceded by a pulse of GHRH and 90% of the GHRH pulses occurred within 20 min preceding a pulse of GH. Leptin tended (P < 0.10) to suppress GH area under the curve (AUC) compared to saline. Concomitantly, NPY tended (P < 0.10) to increase GH AUC, which appeared to be a consequence of increased (P < 0.05) pulse amplitude. Infusion of NPY also increased (P < 0.05) AUC of GHRH relative to saline. No differences were detected among treatments in serum concentrations of insulin-like growth factor-I or its AUC. Sampling CSF from the IIIV appears to be a viable procedure for assessing hypothalamic release of GHRH coincident with anterior pituitary gland secretion of GH in cattle. These data also demonstrate the differential responsiveness of the GH axis to appetite-regulating peptides.     

Injection of neuropeptide Y into the third cerebroventricle differentially influences pituitary secretion of luteinizing hormone and growth hormone in ovariectomized cows.

Hypothalamic neurons that control the luteinizing hormone (LH) and growth hormone (GH) axes are localized in regions that also express neuropeptide Y (NPY). Increased hypothalamic expression of NPY due to diet restriction has been associated with suppressed secretion of LH and enhanced secretion of GH in numerous species. However, these physiological relationships have not been described in cattle. Thus, two studies were conducted to characterize these relationships using ovariectomized (Experiment 1) or ovariectomized estrogen-implanted (Experiment 2) cows. In Experiment 1, four well-nourished, ovariectomized cows received third cerebroventricular (TCV) injections of 50 and 500 micrograms of NPY in a split-plot design. Venous blood was collected at 10-min intervals from -4 hr (pre-injection control period) to +4 hr (postinjection treatment period) relative to TCV injection. NPY suppressed (P < or = 0.04) tonic secretion of LH irrespective of dose and tended to stimulate (P < or = 0.10) an increase in tonic secretion of GH. In Experiment 2, six ovariectomized cows that were well nourished and implanted with estradiol received TCV injections of 0, 50, or 500 micrograms of NPY in a replicated 3 x 3 Latin Square. Both doses of NPY suppressed (P < 0.06) mean concentration of LH relative to the 0-microgram dose. The 50-microgram dose of NPY tended (P < 0.10) to increase the amplitude of GH pulses. In conclusion, TCV injection of NPY suppressed pituitary secretion of LH and simultaneously tended to increase pituitary secretion of GH.     

Combined administration of ghrelin and GHRH synergistically stimulates GH release in Holstein preweaning calves

Ghrelin is a gut peptide which participates in growth regulation through its somatotropic, lipogenic and orexigenic effects. Synergism of ghrelin and growth hormone-releasing hormone (GHRH) on growth hormone (GH) secretion has been reported in humans and rats, but not in domestic animals in vivo. In this study, effects of a combination of ghrelin and GHRH on plasma GH and other metabolic parameters, and changes in plasma active and total ghrelin levels were studied in Holstein bull calves before and after weaning. Six calves were intravenously injected with vehicle (0.1% BSA-saline), ghrelin (1 microg/kg BW), GHRH (0.25 microg/kg BW) or a combination of ghrelin plus GHRH at the age of 5 weeks and 10 weeks (weaning at 6 weeks of age). Ghrelin stimulated GH release with similar potency as GHRH and their combined administration synergistically stimulated GH release in preweaning calves. After weaning, GH responses to ghrelin and GHRH became greater compared with the values of preweaning calves, but a synergistic effect of ghrelin and GHRH was not observed. The GH areas under the concentration curves for 2h post-injection were greater in weaned than in preweaning calves (P<0.05) if ghrelin or GHRH were injected alone, but were similar if ghrelin and GHRH were injected together. Basal plasma active and total ghrelin levels did not change around weaning, but transiently increased after ghrelin injection. Basal plasma insulin, glucose and non-esterified fatty acid levels were reduced after weaning, but no changes by treatments were observed. In conclusion, ghrelin and GHRH synergistically stimulated GH release in preweaning calves, but this effect was lost after weaning.     

Effects of ruminal infusion of volatile fatty acids on plasma concentration of growth hormone and insulin in sheep.

In an initial experiment we observed postprandial changes in plasma concentrations of growth hormone (GH), insulin, glucagon, and somatostatin (SRIF) in sheep. We then examined whether increasing the rumen concentration of volatile fatty acids (VFA) by infusing a VFA mixture at three rates (53.5, 107, and 214 micromol/kg/min for 4 hr) mimicked the postprandial changes in hormone secretion. Feeding significantly (P < 0.05) suppressed the plasma GH concentration for 6 hr, whereas it significantly (P < 0.05) increased plasma concentrations of insulin, glucagon, and SRIF. Plasma glucose levels tended to decrease after feeding but then gradually increased over the prefeeding level (P < 0.05). Intraruminal infusion of the VFA mixture at 107 micromol/kg/min caused similar changes in ruminal VFA concentrations to those seen after feeding. The infusion significantly (P < 0.05) suppressed GH secretion in a dose-dependent manner, whereas it caused a significant (P < 0.05) increase in insulin and glucose concentrations without changing glucagon concentrations. From these results, we conclude that the postprandial change in ruminal VFA concentration may be a physiological signal which modifies GH and insulin secretion in sheep.     

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

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

The effect of lighting conditions on the rhythmicity of growth hormone secretion in Holstein steers

Growth hormone (GH) secretion regularity and the effects of lighting condition and GH‐releasing hormone (GHRH) on GH release were determined in steers. First, steers were kept under 12:12 L : D conditions (light: 06.00–18.00 hours). The animals were then subjected to a 1‐h advancement in lighting on/off conditions (05.00 and 17.00 hours, respectively). Blood was sampled for 24 h at 1‐h interval on the seventh day of each condition. Second, GHRH was injected intravenously (IV) at 12.00 and 00.00 hours under 12:12 L : D and blood was sampled at 15‐min interval for 4‐h (1 h before and 3 h after the injection). Plasma GH concentrations were measured by a radioimmunoassay. Periodicity of GH secretory profile was calculated by power spectrum analysis using the maximum entropy method. Plasma GH concentrations showed a characteristic pattern consisting of four distinct peaks. Mean periodicity of GH secretory profile was 5.7 h, and it was not altered by any change in lighting conditions. IV injection of GHRH increased GH secretion during the day and night. The increase in GH secretory volume after GHRH injection during the night was equal to that during the day. The present results suggest that GH secreted from the anterior pituitary have regularity in steers.     

Neuroregulation of growth hormone secretion in domestic animals

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

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.     

Growth hormone in mares and stallions: pulsatile secretion, response to growth hormone-releasing hormone, and effects of exercise, sexual stimulation, and pharmacological agents.

Short-term patterns of growth hormone (GH) secretion and factors affecting it were studied in mares and stallions. In Exp. 1, hourly blood samples were collected from three mares and three stallions in summer and winter. Although GH concentrations varied in a pulsatile manner in all horses, there was no effect of sex or season (P greater than .1) on plasma GH concentrations and no indication of a diurnal pattern of GH secretion. In Exp. 2, 10-min blood samples were drawn for 8 h from 12 mares; after 6 h, porcine GH-releasing hormone (GHRH) was administered i.v. at 0, 45, 90, or 180 micrograms/mare (three mares per dose). Pulsatile secretion of GH occurred in all mares and averaged 2.4 +/- .3 peaks/6 h; amplitudes were variable and ranged from 2.6 to 74.4 ng/mL. Eight of nine mares responded within 20 min to GHRH injection, but there was no difference (P greater than .1) among the three doses tested. In Exp. 3, plasma GH concentrations in stallions increased (P less than .05) 8- to 10-fold after 5 min of acute physical exercise or exposure to an estrual mare. Restraint via a twitch (5 min) and epinephrine administration (3 mg i.v.) also increased (P less than .05) plasma GH concentrations by approximately fourfold. In Exp. 4 and 5, administration of either .4, 2, or 10 mg of thyrotropin-releasing hormone (TRH) or 100 or 500 mg of sulpiride (a dopamine receptor antagonist) increased (P less than .01) plasma prolactin concentrations but had no effect (P greater than .1) on GH concentrations during the same period of time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ghrelin differentially modulates the GH secretory response to GHRH between the fed and fasted states in sheep

The effect of energy balance on the growth hormone (GH) secretory responsiveness to growth hormone-releasing hormone (GHRH) has not been determined in ruminant animals. Therefore, we examined the effects of intravenous injections of 0, 3.3, and 6.6 μg ghrelin/kg body weight (BW), with and without GHRH at 0.25 μg/kg BW, on GH secretory responsiveness in both the fed and fasted sheep. The injections were carried out at 48 h (Fasting state) and 3 h (Satiety state) after feeding. Blood samples were taken every 10 minutes, from 30 minutes before to 120 minutes after the injection. Low (3.3 μg/kg BW) and high (6.6 μg/kg BW) doses of ghrelin stimulated GH secretion significantly (P < .05) greater in the Satiety state than in the Fasting state. Growth hormone-releasing hormone plus both doses of ghrelin stimulated GH secretion significantly (P < .05) greater in the Satiety state than in the Fasting state. Ghrelin and GHRH exerted a synergistic effect in the Satiety state, but not in the Fasting state. Plasma ghrelin levels were maintained significantly (P < .05) greater in the Fasting state than in the Satiety state except the temporal increases after ghrelin administration. Plasma free fatty acid (FFA) concentrations were significantly (P < .01) greater in the Fasting state than in the Satiety state. In conclusion, the present study has demonstrated for the first time that ghrelin differentially modulates GH secretory response to GHRH according to feeding states in ruminant animals.     

Pulsatile secretion pattern of growth hormone in dogs with pituitary-dependent hyperadrenocorticism

The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.     

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.