Abstract

PIP: A study assessing the effects of estrogen on the pituitary-adrenal axis in rats is reported. In a series of experiments, rats were subjected to single and multiple doses of ethinyl estradiol (EE) and injections of ACTH. Administration of single doses of EE to quiescent rats brought increased plasma and adrenal gland corticosterone concentrations and in vitro corticosteroid production. In animals stressed by ether vapor, the plasma and in vitro corticosterone values were 40% lower than in controls although adrenal corticosterone levels were higher. Treatment with 500 mcg/kg EE per day for 7 days resulted in loss of body weight and hypertrophied, hyperdemic adrenal and pituitary glands in rats sacrificed 1 day after treatment. Rats studied 9 days after treatment showed normal growth and a regression in adrenal size but not in pituitary size. Plasma corticosterone concentration was unchanged 1 day after the 7-day treatment, adrenal weight increased by 58%, and in vivo steroid production was reduced suggesting a distinct hypersecretion of ACTH. Plasma protein binding capacity for corticosterone was unchanged by the 7-day treatment. After 9 days of rest from the EE regimen, an ACTH injection restored in vitro corticosteroid production to normal levels and raised plasma and adrenal content levels in stressed rats which suggests that the adrenal gland regained its function more quickly than the pituitary. Injection with long-acting ACTH caused a 56% increase in adrenal weight and no change in pituitary weight. Adrenal activity was not changed by ACTH treatment suggesting that the adrenal gland was insensitive to an acute release of endogenous ACTH. Inhibition of the pituitary-adrenal response to stress is most likely caused by inhibition of cholesterol synthesis although lack of precursor corticoid secretion due to exhaustion must be considered as a cause. Inhibition of the stress response after extended ACTH treatment is suggested to be due to a decreased sensitivity of the adrenal cortex although a reduction of circulating cholesterol cannot be excluded as a cause.