Withdrawal of endogenous somatostatin induces secretion of growth hormone-releasing factor in rats

Abstract

ABSTRACT Secretion of GH occurs in episodic bursts under the dual control of two hypothalamic peptides, GH-releasing factor (GRF) and GH-inhibiting factor (somatostatin, SRIF). Recent studies in rats suggest that episodic GH secretion is generated by the periodic release of GRF, which is associated with the simultaneous withdrawal of SRIF secretion. To test the possibility that GRF discharge is functionally coupled with the withdrawal of SRIF, we investigated whether acute withdrawal of SRIF can induce GRF release by the rat hypothalamus using highly specific antisera against SRIF and rat GRF. In conscious unrestrained rats, i.v. administration of SRIF antiserum at the period of the GH trough induced a rapid onset of the GH secretory surge with a peak value of 309 ± 67 μg/l (mean ± s.e.m.) 30 min after injection. Pretreatment with antiserum to rat GRF resulted in a ∼83% suppression of the GH surge induced by SRIF antiserum without affecting the trough GH values. GRF antiserum also significantly inhibited the spontaneous GH surge. In urethane-anaesthetized rats, as in conscious rats, an acute phasic GH release was caused by SRIF antiserum despite the interference of anaesthesia with spontaneous GH secretion. A further surge-like GH secretion was not restored during the next several hours, however, with the GH secretory profile being characterized by a tonic increase in the baseline levels of GH. In the anaesthetized rat antiserum to rat GRF, having no effect on basal GH levels, similarly inhibited by ∼66% the acute GH surge induced by SRIF antiserum and decreased by about 30% the later sustained rise in GH. These results indicate that an acute rather than a chronic withdrawal of SRIF can trigger the phasic discharge of GRF by the hypothalamus, and raise the possibility that SRIF, originally isolated as a hypothalamic hypophysiotrophic GH-inhibiting factor, also acts as a GRF-inhibiting factor within the hypothalamus. We suggest that the episodic GH secretion may be initiated by an acute disinhibition of GRF secretion caused by the sudden withdrawal of SRIF. J. Endocr. (1988) 117, 245–252