ADRENOCORTICOTROPIN, PROLACTIN AND BETA-ENDORPHIN STIMULATORY ACTIONSOF ALPHA-2-ADRENOCEPTOR ANTAGONISTS

We studied the effect of glucocorticoid pretreatment, mediobasal hypot halamus lesion (MBHL) and the interaction between clonidine and yohimb ine in male Wistar rats to elucidate the sites and/or mechanisms of en docrine actions of alpha(2)-antagonists. The pretreatment of 1 mg/kg s .c. dexamethasone for 4 days effectively prevented the stimulatory eff ect of alpha(2)-antagonists yohimbine (5 mg/kg i.p.) and CH-38083 (1 m g/kg i.p.) on adrenocorticotropin (ACTH) secretion, while the action o f these antagonists on prolactin (PRL) and beta-endorphin (beta E) rem ained unchanged. The central (i.c.v.) pretreatment of 5 mu g/rat cloni dine failed to antagonize the prolactin (PRL) and beta E releasing eff ect of yohimbine. However, it inhibited the yohimbine-induced ACTH sec retion. MBHL resulted in a significant enhancement in basal plasma PRL and beta-endorphin (beta E) levels. But basal plasma ACTH levels have not been changed. Yohimbine failed to stimulate ACTH secretion in MBH -lesions rats, while PRL and beta E response to the yohimbine was main tained in these animals. This study confirms that the alpha(2)-antagon ists stimulate ACTH secretion by a corticosteroid-sensitive mechanism which is located centrally. In contrast, alpha(2)-antagonists affect P RL and beta E secretion via a corticosteroid-insensitive mechanism loc ated at the periphery, possible within the pituitary gland.