No abstract

To examine the effects of glucocorticoid (GC) on growth hormone (GH)-releasing hormone (GRH) receptor gene expression, a highly-sensitive and quantitative reverse-transcribed polymerase chain reaction (RT-PCR) method was used in this study. Rat anterior pituitary cells were isolated and cultured for 4 days. The cultured cells were treated with dexamethasone for 2, 6, and 24 h. GRH receptor mRNA levels were determined by competitive RT-PCR using a recombinant RNA as the competitor. Dexamethasone significantly increased GRH receptor mRNA levels at 5 nM after 6- and 24 h-incubations, and the maximal effect was found at 25 nM. The GC receptor-specific antagonist, RU 38486 completely eliminated the dexamethasone-induced enhancement of GRH receptor mRNA levels. Dexamethasone did not alter the mRNA levels of beta-actin and prolactin at 5 nM for 24 h, whereas GH mRNA levels were significantly increased by the same treatment. The GH response to GRH was significantly enhanced by the 24-h incubation with 5 nM dexamethasone. These findings suggest that GC stimulates GRH receptor gene expression through the ligand-activated GC receptors in the rat somatotrophs. The direct effects of GC on the GRH receptor gene could explain the enhancement of GRH-induced GH secretion.

Although various pathophysiological effects of interleukin (IL) on the CRF-ACTH-adrenal axis and gonadotropin secretion have been studied extensively, the effects of IL on GH secretion still remain to be elucidated. We investigated the possible effects of IL on GH secretion in six groups of conscious rats. In four groups, IL was administered by continuous iv infusion and in the other two, by intracerebroventricular injection. Saline-treated rats served as controls for these groups. Sequential blood sampling was performed every 20 min in all groups, and the plasma GH concentration was determined by RIA. The expression of hypothalamic c-fos protein in a separate group was examined by immunohistochemistry. Continuous infusion of both IL-1 alpha and IL-1 beta (10 ng/min) significantly inhibited GH surges. The plasma IL-1 level was elevated to 2-3 ng/ml. Continuous iv infusion of IL-2 and IL-6 had no effect on GH secretion. The intracerebroventricular injection of both IL-1 alpha and IL-1 beta significantly inhibited GH surges, and the inhibitory effect was much greater for IL-1 beta than for IL-1 alpha. Continuous iv infusion of IL-1 beta markedly stimulated c-fos expression in specific hypothalamic nuclei, particularly in the paraventricular nucleus. These findings suggest that, in the rat, IL-1 inhibits GH secretion through its peripheral and central actions.

No abstract

Although previous studies have demonstrated that acute hypoglycemia inhibits growth hormone (GH) secretion due to stimulation of hypothalamic somatostatin (SS) neurones in the rat, the effect of hypoglycemia on GH secretion has not yet been elucidated in the mouse. In this study, the effects of insulin-induced hypoglycemia on mouse GH secretion, hypothalamic c-fos expression, GH-releasing hormone (GRH) and SS mRNA levels were investigated in conscious male mice. Seven days after implantation of chronic atrial catheters, blood samples were taken every 20 min from 1200-1600 h under unrestrained conditions. Insulin was administered iv every 20 min from 1200-1240 h to induce moderate hypoglycemia (MH) and severe hypoglycemia (SH), respectively. Expression of hypothalamic c-fos protein was examined 30 min and 60 min after induction of hypoglycemia by immunohistochemistry. Hypothalamic GRH and SS mRNA levels were examined 1 h and 3 h after induction of hypoglycemia by Northern blot analysis. The lowest mean plasma glucose levels after insulin injections were 49.1 +/- 4.1 mg/dl and 34.2 +/- 5.6 mg/dl in conscious mice, respectively. However, pulsatile GH secretion was not significantly altered in either group. Although both MH and SH markedly stimulated c-fos expression in specific hypothalamic nuclei including the paraventricular nucleus, they did not induce c-fos protein in the periventricular nucleus. Neither MH nor SH altered hypothalamic GRH or SS mRNA levels. These results suggest that hypoglycemia does not activate SS neurons which inhibit GH secretion in the mouse.