PANHYPOPITUITARISM AS A MODEL TO STUDY THE METABOLISM OF DEHYDROEPIANDROSTERONE (DHEA) IN HUMANS

The physiological importance and therapeutical interest of dehydroepia ndrosterone (DHEA) and its sulfate ester (DHEAS), are still controvers ial. Panhypopituitarism is characterized by the absence of secretion o f adrenal and gonadal steroids and thus the production of their metabo lites. The conversion of DHEA given orally into Delta 5 derivatives. a ndrogens, androgen metabolites, and estrogens was studied in ten patie nts with complete panhypopituitarism. Sex steroid therapy was withdraw n for at least 2 months. Each patient received, at 1-month intervals a nd in a random order, two single oral doses of DHEA (50 mg and 200 mg) and placebo. During each treatment, urine samples were collected for 24 h, and blood samples were drawn at hourly intervals For 8 h. In pat ients with pituitary deficiency, plasma DHEA and DHEAS were not detect able and increased, with the 50 mg dose, up to levels observed in youn g adults. The administration of 200 mg of DHEA induced an increase of both steroids to supraphysiological plasma levels. A small increase of Delta 5-androstenediol was observed. In contrast, the increase of pla sma Delta 4-androstenedione was important and dose dependent. DHEA was also converted into the potent sex steroid testosterone (T). The admi nistration of a 50 mg dose of DHEA restored plasma T to levels similar to those observed in young women. The 200 mg dose induced an importan t increase of plasma T, slightly below the levels observed in normal m en. The increase of plasma dihydrotestosterone levels was small at bot h doses of DHEA, in contrast with the large conversion of DHEA into an drosterone glucuronide and androstanediol glucuronide. Finally, DHEA a dministration induced a significant and dose dependent increase of pla sma estrogens and particularly of Estradiol.In conclusion, this short term study demonstrates that: 1) panhypopituitarism is a model of inte rest to study the metabolism of DHEA; 2) in the absence of pituitary h ormones and of adrenal and gonadal steroids, DHEA given orally is main ly converted into Delta 4 derivatives, which in turn are strongly meta bolized into 5 alpha-3keto-reduced steroids; 3) a significant increase of sex active hormones was observed in plasma after 200 and even 50 m g of DHEA. Thus, biotransformation of DHEA into potent androgens and e strogens may explain several of the reported beneficial actions of thi s steroid in aging people.