ROLE OF GROWTH-HORMONE (GH)-RELEASING HORMONE AND SOMATOSTATIN IN THEMEDIATION OF CLONIDINE-INDUCED GH RELEASE IN SHEEP

GH secretion is stimulated by the administration of an alpha(2)-adrene rgic agonist, clonidine, in several species, including man. This actio n is probably mediated at the level of the hypothalamus, where the dru g may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to c ollect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. C lonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorde d during the same period. Next, we tested the effect of clonidine in s heep actively immunized against GHRH or SRIH. The alpha(2)-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas im munization against SRIH did not modify the GH response. Finally, we ob served that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect i s mediated through changes in GHRH, but not SRIH, release into hypophy sial portal blood.