Increase In Growth Hormone Release Research Articles

Neuroendocrine regulation of growth hormone secretion in sheep. VII. Effects of GABA

The effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) administration of γ aminobutyric acid (GABA) on plasma growth hormone (GH) concentrations have been examined in sheep. Intravenous administration of GABA resulted in a rapid, significant ( P<0.001) increase in plasma GH. Administration of 10 mg of GABA i.c.v. produced a significant ( P<0.001) increase in GH release. By contrast, 100 mg given i.c.v. was inhibitory and resulted in a decrease ( P<0.05) in plasma GH levels. Concurrent administration of somatostatin (0.5 μg/min i.v. over 1 h) did not alter the plasma GH response to 10 mg GABA given i.c.v. These data are consistent with the concept of dual sites of action for GABA in regulating GH release in sheep, but the exact mechanism through which this effect is mediated remains unclear.

A new gonadotropin-releasing hormone (GnRH) superagonist in goldfish: influence of dialkyl- d-homoarginine at position 6 on gonadotropin-II and growth hormone release

The two native forms of gonadotropin-releasing hormones (GnRH) present in goldfish, salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), stimulate gonadotropin-II (GTH-II) and growth hormone (GH) release both in vivo and in vitro. In our previous study using perifused goldfish pituitary fragments, many mammalian GnRH antagonists, especially those with d-Arg 6, showed weak to strong stimulation of GTH-II and GH release. In the present study, the dose-related stimulation of GTH-II and GH release by [Ac-D(2)-Nal 1, 4Cl- d-Phe 2, d-Trp 3, d-Arg 6, Trp 7, d-Ala 10] mGnRH (analog J) and [Ac-D(2)-Nal 1, 4Cl- d-Phe 2, d-Trp 3, d-hArg(Et 2) 6, d-Ala 10] mGnRH (analog K) was demonstrated; the stimulatory potency of both analogs was significantly lower than that of native sGnRH. In the presence of analogs J and K, cGnRH-II stimulated GTH-II release was significantly suppressed. Further, GTH-II and GH stimulation by 2 μM of analog K was significantly suppressed by a ‘true’ GnRH antagonist, [Ac- δ 3-Pro 1, 4FD-Phe 2, d-Trp 3,6] mGnRH (analog E). These results indicate that analogs J and K increase GTH-II and GH release in goldfish by acting on GnRH receptors on gonadotrophs and somatotrophs. Since analog K, having [ d-hArg(Et 2) 6], strongly stimulated GTH-II release, the potency of [ d-hArg(Et 2) 6] or [ d-hArg(CH 2CF 3) 2 6] substituted analogs to stimulate GTH-II and GH release from the perifused goldfish pituitary fragments was tested. Among the peptides tested, [ d-hArg(Et 2) 6, Pro 9-NHEt] sGnRH had a higher potency in stimulating GTH-II release than any other analog tested in the present or in previous studies. For stimulation of GH release, [ d-hArg(Et 2) 6, Pro 9-NHEt] sGnRH and [ d-Arg 6, Pro 9-NHEt] sGnRH were the most potent analogs tested; analogs of mGnRH were less potent than sGnRH, indicating the importance of Trp 7, Leu 8 residues in the native peptide. These results suggest the importance of [ d-Arg 6] or alkylated [ d-Arg 6] in determining the intrinsic activity and potency of GnRH peptides in goldfish.

Alpha-1-Noradrenergic Inhibition of Growth Hormone Secretion Is Mediated through the Paraventricular Hypothalamic Nucleus in Male Rats

In the present work we investigated a possible role of an alpha 1-noradrenergic (NA) pathway involving the hypothalamic paraventricular nucleus (PVN) in the central regulation of growth hormone (GH) release. A week after bilateral electrolytic lesions of the PVN, pulsatile GH-secretory patterns were monitored in unanesthetized, freely moving control or lesioned male rats. While the pulsatility of GH secretion was maintained, the amplitude of the pulses and the area under the curve during an 8-hour sampling period were twice as high in PVN-lesioned than in control rats. Trough levels of GH were similar in the two groups. Inactivation of PVN alpha 1-receptors by local infusion of an alpha 1-NA antagonist, prazosin (50 ng/rat), also induced an increase in GH release. In control animals, intravenous injection of the alpha 1-NA agonist methoxamine (0.02 mg/100 g body weight) elicited a decrease in GH release but was ineffective when administered to PVN-lesioned rats. These data show that alpha 1-NA receptors, mediating GH inhibition, are located in the PVN. In light of the analogous effects observed herein on PVN-lesioned animals and, previously, after locus coeruleus (LC) lesions it is suggested that GH inhibition by the LC is relayed by the PVN via a local alpha 1-receptor population.

Negative regulation of hypothalamic growth hormone-releasing factor messenger ribonucleic acid by growth hormone and insulin-like growth factor I.

Increased growth hormone-releasing factor messenger ribonucleic acid (GRF mRNA) and decreased somatostatin (SRIF) mRNA levels have been reported in the hypothalamus of hypophysectomized rats as well as of dwarf mice. In order to elucidate the effect of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis on hypothalamic GRF and SRIF synthesis, we measured levels of mRNA coding for GRF and SRIF and for pituitary GH in pubertal male rats treated for 3 weeks with antirat GRF gamma-globulin (GRF-ab), anti-SRIF gamma-globulin (SRIF-ab) or both. Immunoneutralization of circulating endogenous GRF resulted in a marked decrease in serum IGF-I and pituitary GH mRNA levels in Northern blot analysis, whereas it caused a significant increase in GRF mRNA levels in the arcuate nucleus as assessed by both Northern blot and in situ hybridization analysis. SRIF mRNA levels in the periventricular nucleus were slightly decreased by GRF-ab treatment when analyzed by in situ hybridization, but not significantly after Northern blot analysis. Immunoneutralization of circulating endogenous SRIF failed to affect mRNA levels of hypothalamic GRF and SRIF but caused a slight reduction in pituitary GH mRNA levels. Levels of mRNA coding for hypothalamic GRF and pituitary GH were also measured by Northern blot analysis in young male rats treated with rat GRF-ab for 2 weeks and replaced with rat GH or IGF-I for the second 1 week. Replacement with either rat GH or IGF-I suppressed the increased hypothalamic GRF mRNA levels. These data indicate that endogenous GRF is essential for normal synthesis of pituitary GH and that both GH and IGF-I negatively regulate the synthesis of hypothalamic GRF.

Effect of exposure to low level lead on growth and growth hormone release in rats

This study was undertaken to examine the effect of exposure to low level lead on growth and growth hormone (GH) release. Female pups exposed to lead beginning in utero were smaller than controls on postnatal day 7 ( P = 0.06). There was no corresponding effect in males. No overall differences in body weights were detected in either sex with respect to treatment effect. No differences in food or water intake were observed at any time. Pituitaries from 49-day-old lead-treated pups responded to in vitro incubation with growth hormone releasing factor (GRF) with a smaller increase in GH release than those from control pups ( P = 0.08). In the case of the dams, lead did not affect body weight, body length, food consumption or pituitary responsiveness; however, water consumption was significantly increased in the lactating dam ( P<0.05). Interestingly, blood lead content in 5-day old pups (43.3±2.7 μg/dl) exposed to lead in utero was more than twice that of their 49-day-old litter-mates (18.9±0.7 μg/dl). At 49 days blood lead levels in female pups (19.94 ± 0.8 μg/dl) were significantly higher than those of male pups (17.00 ± 1.1 μg/dl). Maternal blood lead levels on the same day averaged 22.7 ± 2.5 μg/dl. This study suggests that exposure to a low level of lead can reduce pituitary responsiveness to a hypothalamic stimulus. In addition, the data reinforce the importance of considering age and sex when evaluating the toxic effects of lead.

Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma

The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1-44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1-44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125-2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992 +/- 68-1872 +/- 32 ng.1.7 x 10(5) cells-1 x 3 h-1), similar to that observed with synthetic GHRH(1-44)NH2. (control value 640 +/- 30 ng.1.7 x 10(5) cells-1 x 3 h-1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm.

The regulatory effects of thyrotropin-releasing hormone on growth hormone secretion from the pituitary of common carp in vitro

The effects of thyrotropin-releasing hormone (TRH) on growth hormone (GH) and gonadotropin (GtH) release, and the influences of somatostatin (SRIF), the dopamine agonist apomorphine (APO) and extracellular calcium on basal and TRH-induced GH release were examined using an in vitro perifusion system for pituitary fragments of common carp (Cyprinus carpio). Five minute pulses of different dosages of TRH stimulated a rapid and dose-dependent increase in GH release from the perifused pituitary fragments with an ED50 of 9.7 ± 2.3 nM. TRH was ineffective on GtH release. SRIF significantly inhibited basal and TRH-induced GH release from the perifused pituitary fragments, and the effects of SRIF were dose-dependent. APO induced a dose-dependent increase in basal and TRH-stimulated GH release from the perifused pituitary fragments. Increasing the concentrations of extracellular calcium from 0 mM to 1.25 mM resulted in an increase in basal and TRH-induced GH release. The high dose of calcium (6.25 mM) caused a slight decrease in basal and TRH-induced GH release compared with those at a concentration of 1.25 mM.

Growth Hormone and Gonadotropin Secretion in the Common Carp ( Cyprinus carpio L.): In Vitro Interactions of Gonadotropin-Releasing Hormone, Somatostatin, and the Dopamine Agonist Apomorphine

The effects of salmon gonadotropin-releasing hormone (sGnRH) and the superactive agonist d-Arg 6, Pro 9NEt]-sGnRH (sGnRH-A) on growth hormone (GH) and gonadotropin (GtH) release were examined using a perifusion system for pituitary fragments of the common carp ( Cyprinus carpio). Perifusion of 2-min pulses of different concentrations of sGnRH or sGnRH-A stimulated a rapid and dose-dependent increase in GH release; ED 50 values for sGnRH and sGnRH-A in stimulating GH release were 2.8 ± 0.7 and 0.5 ± 0.1 n M, respectively, indicating that the superactivity of sGnRH-A for stimulation of GtH release also applies in induction of GH release. Exposure of the pituitary fragments to 10 n M sGnRH or sGnRH-A alone resulted in increases in GH and GtH release on a similar temporal course. Apomorphine (10, 100, and 1000 n M) significantly inhibited basal and GnRH-induced GtH release in a dose-dependent manner and significantly stimulated basal GH release; however, APO did not enhance GnRH-induced GH release. Somatostatin (100 n M) significantly blocked basal release and 10 n M sGnRH- and sGnRH-A-induced GH release, but was ineffective on GtH release. Treatment with somatostatin (100 n M) in combination with apomorphine (100 n M) caused an increase in sGnRH-induced GH release compared to treatment with somatostatin alone; whereas, on GtH there was a significant decrease in basal and GnRH-induced levels, compared to treatment with somatostatin alone. These results indicate that GH release in common carp is regulated by somatostatin as GH release inhibitor. sGnRH and sGnRH-A act as GH-releasing factors; the mechanisms by which GnRH stimulates GH and GtH secretion are independent. The dopamine agonist apomorphine stimulates GH release and inhibits GtH release directly at the pituitary level.

Interactions between the effects of opioid, serotonin and alpha-2-adrenergic receptor agonists on growth hormone release in the male rat. Intravenous administration.

This study was performed to identify low-dose drug combinations which have stimulatory effects on short-term growth hormone (GH) release when given intravenously to male rats. Rats were given intravenous combinations of the lowest doses of drugs which had increased GH release when given individually. Combinations of clonidine, 6 and 30 micrograms/kg, and the serotonin agonist quipazine 160 micrograms/kg had an additive effect on GH release. Almost all combinations of morphine, 40 and 200 micrograms/kg, with clonidine and quipazine stimulated GH release, but this release was less than additive, and there were significant negative interactions between morphine and clonidine (p = 0.03), morphine and quipazine (p = 0.005) and the three drugs together (p = 0.03). Agonist-antagonist studies were performed in an attempt to further define these interactions. Naloxone 5 mg/kg i.v. inhibited GH release due to morphine 200 micrograms/kg, but not quipazine 160 micrograms/kg or clonidine 6 and 30 micrograms/kg. The alpha 2 antagonist idazoxan (2 mg/kg i.v.) prevented release due to intravenous clonidine, morphine and quipazine, but not GH-releasing factor (GRF) 25 micrograms/kg. The 5-hydroxytryptamine antagonist cyproheptadine (0.5 mg/kg i.v.) blocked release due to quipazine and clonidine 30 micrograms/kg, but not morphine 40 and 200 micrograms/kg or GRF. The results of these agonist-antagonist studies do not provide a consistent explanation for the observed interactions. These results indicate that in whole animal studies (1) additive or synergistic drug combinations cannot generally be predicted, (2) less than additive interactions of agonists regularly occur and (3) antagonists are unhelpful in dissecting the nature of the negative interactions.

Interactions between the effects of opioid, serotonin and alpha-2-adrenergic receptor agonists on growth hormone release in the male rat. Intrahypothalamic administration.

In a previous study, we identified a number of negative interactions between the growth hormone (GH)-releasing effects of opioid, alpha 2 and serotonin agonists when given intravenously together to male rats. To further characterise these interactions, conscious male rats were given unilateral intrahypothalamic injections of clonidine, the serotonin agonist quipazine and a mu opioid agonist (DAGO), and plasma GH levels were measured. Injection of all three drugs separately into the mediobasal hypothalamus (MBH) increased GH release. Combinations of DAGO-clonidine (p = 0.04), clonidine-quipazine (p = 0.04) and DAGO-clonidine-quipazine (p = 0.04) produced significantly less than additive GH release, whereas DAGO-quipazine produced additive release. MBH injection of the alpha 2 antagonist idazoxan 10 nmol prevented the GH rise due to clonidine, but did not inhibit release due to DAGO. Injection of DAGO and clonidine but not quipazine into the preoptic-anterior hypothalamic area (PO/AHA) increased GH release, and combination injections of DAGO and clonidine produced additive release. PO/AHA idazoxan 10 nmol prevented GH release caused by both clonidine and DAGO, suggesting that idazoxan prevents opioid-induced as well as clonidine-induced suppression of somatostatin release. The inability of MBH idazoxan to block DAGO-induced GH release suggests that opioid-adrenergic interactions here are not due to an opioid GH-releasing action exerted through catecholaminergic pathways. The negative interaction previously identified between intravenous opioids and quipazine probably occurs outside the hypothalamus.

Cortisone effects on growth, food efficiency, and in vitro growth hormone release

Cortisone effects on growth, food efficiency, and in vitro growth hormone release. These studies were designed to investigate the cause of growth retardation during glucocorticoid treatment in rats. In young animals, body weights and amounts of food consumed were measured at two-day intervals, beginning at 29 days of age. Average food intake and food efficiency were calculated. Animals were treated with cortisone (CORT, 5 mg/rat/day, s.c.) or saline (SAL) for eight days between 37 and 44 days. Growth hormone (GH) release by dispersed pituitary cells in response to nine concentrations of GH-releasing hormone (GHRH) were tested by in vitro perifusion at 45 and 73 days. As previously shown, CORT caused a cessation of growth during the treatment period, and body weight failed to catch up. Food efficiency was decreased during CORT treatment. All parameters of in vitro GH release including basal GH secretory rate, overall GH response to GHRH, and the GHRH concentration-response curves were significantly increased by CORT in the 45-day-old animals. An age-related increase in GH release was also observed between the 45 and 73 day saline-treated animals. These results support the hypothesis that glucocorticoids inhibit growth by induction of changes in food metabolism and GH secretion. The effect on the pituitary gland itself paradoxically involves an increase in GH secretory capacity in response to GHRH.

The effects of pituitary stalk transection, hypophysectomy and thyroid hormone status on insulin-like growth factor 2-, growth hormone releasing hormone-, and somatostatin mRNA prevalence in rat brain

We have used in situ hybridization histochemistry to determine the effects of pituitary stalk transection, hypophysectomy and drug-induced changes in thyroid status on mRNA levels encoding insulin-like growth factor 2, somatostatin, and growth hormone-releasing factor in the choroid plexus, hypothalamic periventricular nucleus, and arcuate nucleus, respectively. Pituitary stalk transection and hypophysectomy in Sprague-Dawley rats decreased insulin-like growth factor 2 and somatostatin mRNA and increased growth hormone-releasing factor mRNA. In each case, the effect of hypophysectomy exceeded that of pituitary stalk transection. Treatment with propylthiouracil for 10 days decreased somatostatin mRNA, markedly increased growth hormone-releasing factor mRNA but had no significant effect on insulin-like growth factor 2 mRNA. Treatment with triiodothyronine had no effect on the mRNAs measured. These findings corroborate the clinical observation of abnormal somatic growth in disturbances of thyroid and growth hormone status and provide further evidence of the effects of these metabolic disturbances and of pituitary disconnection and hypophysectomy on insulin-like growth factor 2 mRNA prevalence.

Cortisone effects on growth, food efficiency, and in vitro growth hormone release

These studies were designed to investigate the cause of growth retardation during glucocorticoid treatment in rats. In young animals, body weights and amounts of food consumed were measured at two-day intervals, beginning at 29 days of age. Average food intake and food efficiency were calculated. Animals were treated with cortisone (CORT, 5 mg/rat/day, s.c.) or saline (SAL) for eight days between 37 and 44 days. Growth hormone (GH) release by dispersed pituitary cells in response to nine concentrations of GH-releasing hormone (GHRH) were tested by in vitro perifusion at 45 and 73 days. As previously shown, CORT caused a cessation of growth during the treatment period, and body weight failed to catch up. Food efficiency was decreased during CORT treatment. All parameters of in vitro GH release including basal GH secretory rate, overall GH response to GHRH, and the GHRH concentration-response curves were significantly increased by CORT in the 45-day-old animals. An age-related increase in GH release was also observed between the 45 and 73 day saline-treated animals. These results support the hypothesis that glucocorticoids inhibit growth by induction of changes in food metabolism and GH secretion. The effect on the pituitary gland itself paradoxically involves an increase in GH secretory capacity in response to GHRH.

Increased growth hormone response to growth hormone releasing hormone induced by erythropoietin in uraemic patients

This study was designed to assess the response of growth hormone (GH) to growth hormone releasing hormone (GHRH) and the possible interaction of acutely administered recombinant human erythropoietin (rhEPO) on GH response to GHRH in a group of uraemic patients. Eight patients on maintenance haemodialysis, not previously treated with rhEPO, and six healthy controls were tested with GHRH (100 micrograms i.v. in bolus), and with GHRH (100 micrograms i.v. in bolus) plus rhEPO (40 U/kg in constant infusion for 30 min) on different days. GHRH injection provoked a GH release in five out of eight uraemic patients; the overall mean response did not differ significantly from the GH response obtained in controls (P = 0.30). Erythropoietin infusion significantly increased GH release after GHRH (P less than 0.01 at 15, 30, 45, 60 min after GHRH injection) in uraemic patients; in controls, on the contrary, stimulation with GHRH plus rhEPO did not induce a greater increase of GH release compared with that observed after GHRH alone (mean GH peak 37.66 +/- 7.68 mU/l after GHRH; and 38.0 +/- 9.18 mU/l after GHRH plus rhEPO; P greater than 0.5). In this study acutely administered rhEPO significantly potentiated the GH response to GHRH in uraemic patients whereas the same effect was not demonstrable in subjects with normal renal function.

INFLUENCE OF GROWTH HORMONE-RELEASING FACTOR AND (OR) THYROTROPIN-RELEASING FACTOR ON SOW BLOOD COMPONENTS, MILK COMPOSITION AND PIGLET PERFORMANCE

Two experiments were conducted using a 2 × 2 factorial design to determine the effect of porcine growth hormone-releasing factor (pGRF(1–29) NH2) and (or) thyrotropin-releasing factor (TRF) on the endocrine and metabolic status of sows as well as production performance during the lactation period. In exp. 1, sows were assigned to the following treatments: control (vehicle 3 mL, n = 6); pGRF(1–29)NH2 (20 μg kg−1, n = 7);TRF(1 μ kg−1, n = 7); pGRF + TRF (20 and 1 μg kg−1, respectively, n = 6). In the second experiment, 24 sows were equally distributed to the same treatments as in exp. 1 but the dose of TRF was increased to 9 μg kg−1. During lactation (28 d), releasing factors were administered subcutaneously at 10:00 h and 16:00 h from days 5 to 25, inclusively. Serum growth hormone (GH), thyroxine (T4) and prolactin (PRL) concentrations were assayed on days 5, 15 and 25. In both experiments, TRF stimulated T4 release on all sampling days. However, with advancing lactation and/or days of injection, basal and TRF-stimulated T4 levels decreased (P &lt; 0.05). In the second experiment, GRF increased GH release on each sampling day while saline and TRF had no effect (P &gt; 0.05). The GH response to GRF was higher (P &lt; 0.05) on days 15 and 25 compared to day 5 and higher on day 25 compared to day 15. Also, in both experiments, TRF stimulated PRL release on all sampling days. With advancing lactation and/or days of injection, basal and TRF stimulated PRL release decreased (P &lt; 0.05). In exp. 1, serum creatinine (P &lt; 0.01) and blood urea nitrogen (P = 0.06) concentrations were decreased by GRF treatment while TRF treatment increased (P &lt; 0.01) blood glucose and decreased (P = 0.07) serum cholesterol concentrations. In both experiments, milk yield, fat, protein and lactose contents were unaffected (P &gt; 0.05). Piglet body weight gain and sow weight loss were not affected (P &lt; 0.05) by treatments. Results showed that GRF increases the release of GH while TRF stimulates T4 and PRL release during lactation. However, none of these endocrine modifications influenced production performance. Key words: GRF, TRF, hormone, milk, sow, piglet

Direct Stimulation of Growth Hormone Secretion by Galanin in the Domestic Fowl*

Abstract Galanin, a novel peptide originally isolated from porcine intestine, has a wide distribution in the nervous system and is known to enhance the release of growth hormone in mammals, though the mechanism of its actions is still subject to debate. In the current study, the effects of galanin on growth hormone secretion in the domestic fowl were investigated. Intravenous injections of galanin into both 8-week old and 18-week old female Hubbard broilers produced marked increases in plasma growth hormone, similar in magnitude to that evoked by human growth hormone-releasing factor. Galanin produced dose-related increases in growth hormone release, with a peak response occurring within 10 min of administration. Growth hormone release in response to a maximal challenge of growth hormone-releasing factor was further augmented when galanin was given at the same time. Galanin stimulated growth hormone release from chick hemipituitary glands in vitro, a response which was not dependent upon hypothalamic input. In addition, galanin potentiated the actions of growth hormone-releasing factor on growth hormone release in vitro and these responses were reversed by somatostatin. These results show that galanin is able to stimulate growth hormone release in the domestic fowl by acting directly on the pituitary gland.

Growth hormone secretion during longterm incubation of the pituitary of the Japanese eel, Anguilla japonica

Growth hormone (GH) secretion from organ-cultured pituitaries of the eel (Anguilla japonica) was studied during incubation in a defined medium for 2 weeks, using a homologous radioimmunoassay which does not distinguish between the two molecular forms of eel GH. The total amount of GH secreted increased gradually during the incubation period; so that the amount of GH released on day 14 was about 30 times greater than that on day 1. On day 14, the proportion of GH released relative to the total amount of GH present (the sum of GH released into the medium and residual content in the pituitary) was 96% and the amount produced on day 14 was 4 times greater than the content in the unincubated pituitary. Somatostatin (SRIF, 1.8 × 10(-7) M) inhibited the increase in GH release. On day 7, the proportion of GH released by pituitaries treated with SRIF (28%) was less than that released by the control pituitary (91%). There was no significant difference in GH release between the pituitaries incubated in isotonic medium (300 mOsm) and those in hypotonic medium (240 mOsm) for 2 weeks except for the first 3 days, when the pituitaries in hypotonic medium secreted significantly greater amounts of GH than those incubated under isotonic condition. Hypertonic medium (350 mOsm) had no effect on GH release except for significant inhibition on days 6 and 14. When secretion of the two forms of GH (GH I and II) was examined after separation by polyacrylamide gel electrophoresis followed by densitometry, slightly more GH I tended to be secreted than GH II during the culture period, although the effects of SRIF and osmolality of the media on GH I release were similar to those on GH II. It is concluded that GH secretion and production in the eel is mainly under the inhibitory control of hypothalamus, and that osmolality has a minimum influence on the GH release.

Differential Actions of Dopamine Receptor Subtypes on Gonadotropin and Growth Hormone Release in vitro in Goldfish

Incubation of cultured goldfish pituitary cells with 10 nM to 1 microM apomorphine (APO), a non-selective dopamine agonist, increased growth hormone (GH) release in a dose-dependent manner. GH release was also stimulated in a dose-dependent manner by 0.1 nM to 1 microM salmon gonadotropin (GTH)-releasing hormone (sGnRH), sGnRH analog, and chicken GnRH-II (cGnRH-II). The magnitude of GH responses to 1 microM GnRHs were less than that to 1 microM APO. GH responses to 10 nM to 1 microM APO were not significantly increased by the addition of GnRHs. Static incubations with 0.1 nM to 1 microM of the dopamine D1 agonist SKF38393 did not alter basal GTH release, or the GTH responses to 10 nM sGnRH and cGnRH-II. In contrast, the D1 agonist SKF38393 significantly increased basal GH secretion with maximal stimulation achieved at 100 nM concentration, and GH responses to 10 nM sGnRH and 10 nM cGnRH-II were enhanced by simultaneous applications of SKF38393. Incubation with 1 microM of the D2 agonist LY171555 decreased basal GTH release. Additions of 0.1 nM to 1 microM LY171555 caused dose-dependent decreases in the GTH secretion induced by 10 nM sGnRH and cGnRH-II. In contrast, basal and GnRH-stimulated GH release were not affected by coincubations with LY171555. The D1 antagonist SKF83566 and the D2 antagonist domperidone, at 1 microM concentrations, specifically blocked the D1 agonist SKF38393-stimulated increase in GH release and the D2 agonist LY171555-induced depression of GTH secretion, respectively. In cell column perifusion studies, the D1 agonist SKF38393 at 0.1 nM to 1 microM had no effects on GTH release, but significantly elevated GH secretion rates when applied at 0.1-1 microM concentrations. The GH release induced by 1 microM SKF38393 was significantly reduced by simultaneous perifusion with 1 microM of the D1 antagonist SKF83566. Treatments with SKF38393 and/or SKF83566 did not affect net GTH and GH responses to sGnRH challenges. In contrast, perifusion with 0.1 and 1 microM of the D2 agonist LY171555 depressed basal as well as sGnRH-induced GTH responses. These effects of 1 microM LY171555 were completely blocked by simultaneous applications of 1 microM domperidone, a D2 antagonist. Treatments with these D2 selective drugs did not affect basal and sGnRH-stimulated GH release. These results indicate that in cultured goldfish pituitary cells, activation of dopamine D1- and D2-like receptors specifically stimulates GH release and inhibits both basal and stimulated GTH secretion, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. I. Effects of growth hormone releasing factor and somatostatin.

As growth hormone has been implicated in the "dawn phenomenon," an early morning rise in serum glucose, we have studied the control of growth hormone release in diabetes using an acutely dispersed system of adenohypophysial cells from normal or diabetic rats (65 mg/kg streptozotocin, 8 days before sacrifice; serum glucose, 490 +/- 17 mg/dL). Growth hormone release is normally controlled by the two hypothalamic hormones, growth hormone releasing factor and somatostatin. We have found cells of the diabetic rats exhibit changes in sensitivity that result in increased growth hormone release in static incubation. In normal cells, rat growth hormone releasing factor increases growth hormone release three- to four-fold with an EC50 of 151 +/- 27 pM (n = 7). In contrast, in cells from diabetic rats, there was a significant (twofold) increase in sensitivity to growth hormone releasing factor (EC50 = 75 +/- 15 pM, n = 7) which resulted in increased growth hormone release with lower but not maximal (10 nM) growth hormone releasing factor. Basal nonstimulated release was unchanged. Somatostatin inhibition of stimulated growth hormone release was reduced (n = 7); half-maximal inhibition occurred with 0.21 +/- 0.03 nM (normal) and 0.76 +/- 0.17 nM somatostatin (diabetic). In perifusion the peak secretion rate was significantly lower for diabetic cells stimulated by a maximal dose of growth hormone releasing factor. These studies suggest somatotrophs of diabetic rats have altered sensitivity in vitro to the controlling hormones growth hormone releasing factor and somatostatin.