A Study of Feedback Suppression of ACTH Secretion Utilizing Glucocorticoid Implants in the Hypothalamus: The Comparative Effects of Cortisol, Corticosterone, and their 21-Acetates

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Abstract
The comparative effects of 4 glucocorticoids, cortisol, corticosterone and their respective 21-acetates, on pituitary-adrenal function were studied in the rat. The 4 glucocorticoids and cholesterol were implanted in the median eminence of the hypothalamus and the plasma-corticosterone response to a standard ether stress was studied at intervals ranging from 2-21 days after implantation. Cholesterol was ineffective in suppressing the plasma corticosterone response to ether as was implantation of the glucocorticoids in the cerebral cortex. Cortisol-21-acetate suppressed the response to the standard stress, and produced adrenal atrophy that persisted for at least 21 days. The implanted cortisol-21-acetate pellets were still visible in the region of the median eminence of the hypothalamus 3 weeks after implantation. The other glucocorticoids were effective in suppressing the response to the standard stress at 2 and 4 days, but not 8 days, after implantation. By 14 days after implantation, cortisol, corticosterone and corticosterone-21-acetate were no longer visible at the site of implantation in the median eminence. It is concluded that the rat''s natural glucocorticoid, corticosterone, is less suitable for some studies on the effects of steroid implants in the brain because of its rapid absorption from the site of implantation. On the other hand, cortisol-21-acetate seems eminently suited for such studies because of its slow rate of absorption.