Feedback regulation of growth hormone in the central nervous system of adult, male rats.

Abstract

The function of central catecholaminergic system, growth hormone (GH), and insulin-like growth factor 1 (IGF-I) in the GH feedback mechanism is not fully understood. Mean GH levels in the plasma sequentially sampled from chronically cannulated, unstressed male rats was used to estimate the GH secretion under several experimental conditions. Human (h) GH (15ug/5ul) intracerebroventricular (icv) administration inhibited endogenous GH secretion (1.43 $\pm$ 0.68 vs 20.91 $\pm$ 3.2 ng/ml, p $<$.01). Blockade of D$\sb2$-dopaminergic and alpha$\sb1$- and beta- adrenergic neurotransmission did not restore the GH secretion suppressed by hGH icv. IGF-I antiserum icv alone had no effect on GH secretion with or without the treatment of hGH icv. But in animals passively immunized with somatostatin antisera, IGF-I antiserum icv restored the GH secretion, which was previously inhibited by human GH icv and only partially restored by somatostatin antisera alone (28.96 $\pm$ 2.08 vs 21.16 $\pm$ 1.43 ng/ml, p $<$.05). This stimulatory effect of IGF-I antiserum was attentuated by passive immunization with growth hormone releasing hormone (GHRH) antiserum. IGF-I antiserum icv didn't affect the responsiveness of somatotropes to human GHRH. IGF-I immunoreactivity in the cerebrospinal fluid of the anesthetized animal was elevated 4 hours after hGH icv (5.6 $\pm$.28 vs 3.15 $\pm$.32 ng/ml, p $<$.01), whereas, levels of IGF-I immunoreactivity in the plasma were relatively stable in the 6 hours of sampling period, and they showed no correlation to plasma GH levels observed. Recombinant IGF-I icv suppressed GH secretion but not in a dose-dependent manner, and was completely restored by somatostatin antisera iv. Taken together, these results suggest: (1) the central catecholamine systems tested do not play a major role in GH feedback regulation, (2) IGF-I does not impose a tonic influence on hypothalamus to regulate GH secretion, (3) GH stimulates hypothalamic somatostatin release independent of IGF-I, (4) somatostatin is the major mediator in GH feedback regulation, and (5) hGH icv enhances the influence of IGF-I on the hypothalamus, which in turn inhibits the release of GHRH.