Involvement of Hypothalamic Somatostatin in the Suppression of Growth Hormone Secretion by Central Corticotropin-Releasing Factor in Conscious Male Rats

Abstract

The role of central corticotropin-releasing factor (CRF) in the regulation growth hormone (GH) secretion was studied in freely moving conscious male rats with indwelling intra-atrial and intracerebroventricular (i.c.v.) cannulae. GH measurements in blood samples obtained every 20 min from 10.00 to 14.00 h in control animals injected with saline either intravenously (i.v.) or into the lateral cerebral ventricle revealed that spontaneous GH secretion was pulsatile, and occurred regularly at around 12.00 h. When ovine CRF (10 µg) was injected i.c.v., spontaneous GH secretion was inhibited (mean plasma GH [11.20–13.00 h]: 20 ± 7 ng/ml vs. control: 126 ± 22 ng/ml, p < 0.01). In contrast, the intravenous injection of CRF (10 µg) did not affect spontaneous GH secretion (mean plasma GH [11.20–13.00 h]: 162 ± 25 ng/ml vs. control: 193 ± 31 ng/ml). This GH suppressive action of central CRF was blocked by the i.v. injection (0.5 ml) of antisomatostatin serum (AS), but not of normal sheep serum (NS), (mean plasma GH [11.20–13.00 h]: NS + CRF: 15 ± 2 ng/ml vs. AS + CRF: 202 ± 30 ng/ml, p < 0.01). The mean plasma GH value [11.20–13.00 h] in animals receiving AS and CRF was not significantly different from those in animals receiving saline (i.v.) together with AS. These results suggest a potential inhibitory role of central CRF in the regulation of spontaneous GH secretion in the rat which is mediated by the stimulation of hypothalamic somatostatin.

Effects of Intravenous Corticotropin-Releasing Hormone upon Sleep-Related Growth Hormone Surge and Sleep EEG in Man

“…Central application of o-CRH suppresses spontaneous GH release in the rat [39]. This effect is probably mediated by somatostatin because o-CRH enhances release of this neuropeptide from cultured brain cells [36] and from the hypothalamus of conscious rats [25]. Correspondingly, Par ker et al [35] demonstrated that physiologic nycthemeral GH release was completely inhibited by a somatostatin in fusion.…”

Effects of maternal deprivation on the somatotrophic axis and neuropeptide Y in the hypothalamus and pituitary in female lambs. The histomorphometric study.

“…In rats exposed to stress, CRH stimulates in vitro hypothalamic somatostatin release [23,24] and inhibits GH secretion [10]. Moreover, the action of central CRH in the regulation of GH secretion in rats is mediated by the stimulation of hypothalamic somatostatin [25]. In contrast to rats, where both acute and prolonged stressful stimulation suppress the GH secretion mediated by somatostatin [26], various stressful stimuli elicit an increase of circulating GH in monkeys and humans [27,28].…”

Stimulation and Inhibition of Growth Hormone Secretion by Interleukin-1β; The Involvement of Growth Hormone-Releasing Hormone

“…IL-l-induced CRH release is well documented [3,5,38,42,43] and GH secretion is inhibited by CRH [30,36,37], CRH stimulates the re lease of somatostatin [1,26,34], the hypothalamic neurocrine inhibiting pituitary GH secretion. Somatostatin also inhibits GHRH release [21,25], and antiserum to so matostatin blocks CRH- [20,37] or stress-induced [2,41] suppression of GH secretion. It is suggested, therefore, that with high doses of IL-1, somatostatin secretion is stimulated through IL-l-induced increased release of CRH; somatostatin, in turn, inhibits GHRH release and ultimately suppresses pituitary GH secretion.…”