HIGH BIOAVAILABILITY OF DEHYDROEPIANDROSTERONE ADMINISTERED PERCUTANEOUSLY IN THE RAT

Dehydroepiandrosterone (DHEA) administered percutaneously by twice dai ly application for 7 days to the dorsal skin of the rat stimulates an increase in ventral prostate weight with approximately one third the p otency of the compound given by subcutaneous injection. The doses requ ired to achieve a 50% reversal of the inhibitory effect of orchiectomy are approximately 3 and 1 mg respectively. By the oral route, on the other hand, DHEA has only 10-15% of the activity of the compound given percutaneously. Taking the bioavailability obtained by the subcutaneo us route as 100%, it is estimated that the potencies of DHEA by the pe rcutaneous and oral routes are approximately 33 and 3% respectively. S imilar ratios of activity were obtained when dorsal prostate and semin al vesicle weight were used as parameters of androgenic activity. When examined on an estrogen-sensitive parameter, namely uterine weight in ovariectomized rats, the stimulatory effect of DHEA was much less pot ent than its androgenic activity measured in the male animal, a 50% re versal of the inhibitory effect of ovariectomy on uterine weight being observed at the 3 and 30 mg doses of DHEA administered by the subcuta neous and percutaneous routes respectively. When measured on uterine w eight, percutaneous DHEA thus shows a 10% potency compared with the su bcutaneous route. The sulfate of DHEA (DHEA-S), on the other hand, was approximately 50% as potent as DHEA at increasing ventral prostate we ight after subcutaneous or percutaneous administration. When the effec t was measured on dorsal prostate and seminal vesicle weight, percutan eous' DHEA-S had 10-25% of the activity of DHEA. DHEA decreased serum LH levels in ovariectomized animals, an effect which was completely re versed by treatment with the antiandrogen flutamide. On the other hand , flutamide had no significant effect on the increase in uterine weigh t caused by DHEA, thus suggesting a predominant estrogenic effect of D HEA at the level of the uterus and an androgenic effect on the feedbac k control of LH secretion. The present data show a relatively high bio availability of percutaneous DHEA as measured by its androgenic and/or estrogenic biological activity in well-characterized peripheral targe t intracrine tissues in the rat.