Effect of dehydroepiandrosterone (DHEA) on diethylstilbestrol (DES) induced pituitary hyperplasia

SUÁREZ CECILIA, GARCÍA TORNADÚ I, KHALIL W, BECÚ-VILLALOBOS D

Mendoza

Congreso; XXXII Reunión de la Sociedad Argentina de Farmacología Experimental; 2000

SAFE

The physiological importance and therapeutical interest of DHEA has been outstanded in relation to its action as inhibitor of the promotion and progression of several kinds of tumors, including those of mammary, lung, colon, liver and skin tissues. The aim of this study was to determine the role of DHEA on DES-induced pituitary hyperplasia. Female 60-day-old Sprague-Dawley rats were divided into four treatment groups. DES rats were implanted sc with a 23 mg DES pellet. DHEA rats were implanted sc with two 50 mg DHEA pellets. DHEA/DES rats were implanted sc with a 23 mg DES pellet plus two 50 mg DHEA pellets. Control rats were not implanted. Every week, all rats were weighed, cycled and jugular blood samples were taken under ether anesthesia. After seven weeks, rats were sacrificed. Hypophyses were removed and weighed, and serum prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) plasma content were assayed by RIA. DHEA treatment had a protective effect over rat mortality (0/6 vs 4/6 deaths in DHEA/DES and DES group), reversed the loss of body weight, reduced pituitary hyperplasia (39 +/- 4 mg DHEA/DES vs 69 +/- 18 mg DES) and delayed the continuous estrus onset produced by DES. Both DHEA and DES per se increased serum PRL and GH. However, when administered together, the effect was not additive. On the contrary, DHEA reversed the increased PRL plasma levels induced by DES, specially from the fourth week of treatment onwards (338 + 50 ng/ml DHEA/DES vs 638 + 133 ng/ml DES in the fifth week). We conclude that administration of DHEA has an inhibitory effect over DES-induced endocrine changes, as well as a protective role over other negative side effects produced by estrogen exposure.