Effects of Estradiol on Pituitary-Adrenal Function in Male and Female Rats1

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Abstract
Two weeks after a single injection of polyestradiol phosphate, pituitary weight more than doubled in both male and female rats. Pituitary ACTH content was unchanged in the males but increased 2.5-fold in the female animals. Pituitary RNA and DNA increased in the male rats, whereas only RNA increased in the females. Adrenal weight was increased only in male rats, associated with an increase in adrenal RNA. Adrenal RNA and DNA in female rats were both decreased. Estradiol administration reversed previously reported sex differences in adrenal secretion and peripheral metabolism of corticosterone (Cpd. B). Plasma Cpd. B concentrations after stress or ACTH were increased in treated male rats and unchanged in females. In male animals, estradiol increased hepatic reduction of ring A of Cpd. B in vitro and shortened the biological half-life of Cpd. B in vivo. Converse effects were obtained in females. Following estradiol administration in vivo or after its direct addition in vitro, steroidogenesis was stimulated in adrenal slices from male rats. No change or inhibition was observed in adrenals from intact female donors, but stimulation occurred in glands from oophorectomized rats. The maximal secretion rate of Cpd. B in adrenal venous blood was elevated in males and depressed in females given estradiol. A greater steroid secretion rate was obtained in female control rats compared to male controls. A hypothesis consistent with all the evidence is that the effects of estradiol are related to dose. Small amounts are stimulatory and larger amounts are inhibitory, with respect to both adrenal secretory capacity and peripheral metabolism of Cpd. B.