Amelioration of Cortisone-Induced Pituitary-Adrenal Suppression by Estrad1

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Abstract
Administration of cortisone acetate, 2.5 mg daily for 7 days, to male and female rats reduces both pituitary ACTH content and adrenal weight. Plasma corticosterone concentrations measured at rest and 30 min after ether stress or ACTH injection are decreased in cortisone-treated animals. A greater degree of depression is produced in male rats given steroid than in females. The concomitant administration of a depot ACTH preparation with cortisone leads to an increased plasma corticosterone response to a subsequent test dose of ACTH. However, no change is obtained in the impaired response to stress. Polyestradiol-17β phosphate (Estradurin), administered as a single depot injection of 2 mg/100 g body weight, significantly modifies all the effects of cortisone. Compared to cortisone-treated rats, pituitary ACTH content is higher in unstressed animals and the net falls in ACTH content are significantly greater after stress. Plasma corticosterone responses to both ACTH and stress are enhanced in rats given estradiol as well as cortisone. These data may be explained by stimulatory effects of estradiol on pituitary and adrenal function consistent with previous studies. Sex differences in steroid clearance and the effects of estradiol on the biological half-life of corticosterone may also play a role.