ROLE OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE SUPPRESSION OFLUTEINIZING-HORMONE RELEASE BY DELTA-9-TETRAHYDROCANNABINOL

The ability of cannabinoids to affect anterior pituitary luteinizing h ormone (LH) secretion has been largely attributed to a central nervous system site of action, however, the mechanism(s) by which cannabinoid s alter LH release remains unclear. In the present study, the acute ad ministration of delta-9-tetrahydrocannabinol (THC) produced a dose-rel ated suppression of plasma LH and stimulation of adrenocorticotropin ( ACTH) levels in ovariectomized female rats. To determine if activation oi the hypothalamic-pituitary-adrenal axis was involved in the abilit y of THC to inhibit LH release, female rats were either pretreated wit h the corticotropin-releasing hormone (CRH) receptor antagonist, alpha -helical CRH, or were adrenalectomized prior to acute THC administrati on. in order to assess the roles of CRH and corticosterone in the abil ity of THC to suppress LH secretion, A low dose of THC (0.5 mg/kg b.w. , iv) produced a decrease in plasma LH levels at 20 and 40 min posttre atment in ovariectomized, sham adrenalectomized rats. However, in adre nalectomized animals, plasma LH levels were suppressed at 40 min and r emained decreased at 80 min following THC administration, Thus, the du ration of LH suppression following THC treatment was significantly inc reased in adrenalectomized versus sham adrenalectomized rats (p < 0.05 ). Furthermore, pretreatment with the CRH receptor antagonist, alpha-h elical CRH (100 mu g/5 mu l, icv), 30 min before THC administration, a ttenuated the ability of a high THC dose (1.0 mg/kg) to inhibit LH rel ease in ovariectomized rats. Together, these results demonstrate that THC has significant effects on LH and ACTH secretion in ovariectomized rats and suggest that THC-induced CRH activation, but not corticoster one release, plays a role in the suppression of LH release by cannabin oids.