Pituitary-Adrenal Function in the Rat After Gonadectomy and Gonadal Hormone Replacement1

Gonadectomy in male rats impaired growth but increased pituitary and adrenal weight and adrenal RNA and DNA content. Pituitary ACTH content increased also. Testosterone replacement lowered both ACTH content and adrenal weight to control levels. Estradiol administration increased pituitary ACTH without a further increment in adrenal weight. Gonadectomy and adrenalectomy together increased pituitary ACTH content compared with adrenalectomy alone. Under these conditions, testosterone replacement reduced pituitary ACTH and estradiol administration increased it further. Plasma corticosterone (Cpd. B) concentrations in castrated males at rest, after stress or after ACTH injection did not differ from those observed in intact controls. Biological half-life in vivo was shortened and hepatic inactivation of steroid in vitro was increased. Steroid production by adrenal slices in vitro was diminished by castration, and the output of steroid in adrenal venous blood also decreased. Increased steroid secretion was produced by administration of either gonadal hormone to castrated males. Gonadectomy in female rats resulted in greater body weight and pituitary weight but decreased adrenal weight and RNA content. Pituitary ACTH content was unaffected by oophorectomy but increased after replacement with estradiol, as did adrenal weight. Testosterone administration lowered adrenal weight without change in pituitary ACTH. Gonadectomy and adrenalectomy together decreased ACTH content compared to adrenalectomy alone. Under these conditions, estradiol replacement increased pituitary ACTH and testosterone administration lowered it further. Oophorectomized rats also demonstrated decreased plasma Cpd. B concentrations, prolonged steroid turnover, decreased adrenal steroid production in vitro and diminished steroid output in adrenal venous blood. Both estradiol and testosterone increased adrenal secretion in spayed animals. The data suggest that the gonadal hormones affect pituitary-adrenal function at multiple sites. Testosterone depressed ACTH secretion and steroid clearance but increased adrenal responsiveness to ACTH, whereas estradiol exerted a consistently stimulatory effect.