Cerebral Involvement in the Inhibition of ACTH Secretion by Hydrocortisone

Abstract

Cerebral and pituitary involvement in the feedback regulation of ACTH secretion was investigated by stereotaxic placement of single (roughly 0.2 mg) or double implants of crystalline hydrocortisone acetate in the brain or pituitary of male rats. Compensatory adrenal hypertrophy (CAH) was measured 9–10 days following unilateral adrenalectomy. Single hydrocortisone implants in the median eminence and the anteromedial hypothalamus resulted in abolition of CAH and in atrophy of the remaining adrenal. Ventral prostate weights in these rats were decreased somewhat, but testicular, thyroid and pituitary weights were unchanged, and prostatic, testicular and thyroid histology was normal. Hydrocortisone implants in the lateral basal hypothalamus produced only partial inhibition of CAH, and cholesterol implants in the median eminence had no effect. Single hydrocortisone implants in the pituitary gland were likewise ineffective, as were 3 of 4 double implants in the pituitary. Normal CAH followed single anterior forebrain, posterior diencephalic and cerebellar implants, while responses from other forebrain areas were equivocal. Bilateral implants in the midbrain resulted in slight or no inhibition. It is concluded that the hypothalamus rather than the pituitary should be regarded as the primary locus of feedback inhibition of ACTH by hydrocortisone.