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2-Adrenergic Control of Growth Hormone (GH) Secretion in Conscious Male Rabbits: Involvement of Endogenous GH-Releasing Factor and Somatostatin^*

Third Division, Department of Medicine and Division of Metabolism and Nutrition, International Center for Exchanging Medical Research, Kobe University School of Medicine Kobe 650, Japan

Address all correspondence and requests for reprints to: Dr. Naoto Minamitani, M.D., Third Division, Department of Medicine, Kobe University School of Medicine, 5–1, 7-chome, Kusunoki-cho, Chuohku, Kobe 650, Japan.

Abstract

In an attempt to clarify the regulatory role in GH secretion of central -adrenergic and dopaminergic mechanisms, the effects of iv administration of ¹- and ²-adrenergic antagonists and dopaminergic antagonists were investigated in undisturbed conscious male rabbits. During a 6-h observation period (1030–1630 h), control animals demonstrated spontaneous pulsatile GH secretion with mean (±EM) 6-h GH levels of 6.49 ± 0.54 ng/ml (n = 16). Intravenous injection of yohimbine (YOM; an 2-antagonist), chlorpromazine (CPZ), and haloperidol (HAL; dopamine and -adrenergic antagonists) completely suppressed this pulsatile GH secretion (mean 6-h GH levels, 2.98 ± 0.24, 3.48 ± 0.24, and 2.91 ± 0.29 ng/ml, respectively; P < 0.001), whereas prazosin (an 1-antagonist), pimozide (a selective dopamine antagonist), sulpiride, and YM-09151–2 (YM; D²-specific antagonists) failed to affect the GH secretory pattern (mean 6-h GH levels, 6.61 ±0.73, 6.71 ± 0.56, 5.44 ± 0.44, and 6.87 ± 1.44 ng/ml, respectively). While an iv injection of 2 µg synthetic human GH-releasing factor-(l–44)-NH2 (hGRF) induced GH rises in prazosin-, HAL-, pimozide-, sulpiride-, and YM-treated rabbits as well as control rabbits, YOM and CPZ completely abolished these GH responses to hGRF injection.

An iv injection of 10 ml antisomatostatin -globulin caused a prompt and transient GH rise, followed by a sustained elevation of GH trough levels in normal control rabbits. YOM treatment completely abolished this highly oscillated GH release. However, suppression by YOM or CPZ of hGRF-induced GH rises was significantly reversed by iv administration of 10 ml antisomatostatin -globulin. Therefore, the inhibitory effect of YOM and CPZ on both episodic GH release and hGRF-induced GH rises is due to the enhanced release of somatostatin, with a simultaneous suppression of endogenous GRF. On the other hand, HAL, possessing a weaker -blocking action than CPZ, blunted pulsatile GH secretion, but only modestly suppressed hGRF-induced GH rises.

These results suggest the following. 1) Central ²-adrenergic mechanisms play a more important role in the regulation of GH secretion than ¹-adrenergic mechanisms in the rabbit as well as in other species. 2) The ²-adrenergic blockade causes suppression of the release of hypothalamic GRF and enhanced release of endogenous somatostatin, thereby suppressing GH secretion. Furthermore, hypothalamic GRF neurons may show a more sensitive response to ²-adrenergic blockade than somatostatin neurons. 3) Dopaminergic mechanism has little effect on the regulation of GH secretion in the rabbit.

Footnotes

^* This work was supported in part by research grants from the Japanese Ministry of Health and Welfare; the Japanese Ministry of Education, Science, and Culture; and the Growth Science Foundation, 1987.

Received May 24, 1989.