Endocrine mechanisms of suppressive effect of low dose estrogen-antiandrogen treatment on androgen-dependent organs of male rats.

Abstract

The effects of low doses of hexestrol (Hex) (2-40 micrograms/kg bw) and flutamide (FI) (10 mg/kg bw) on some endocrine mechanisms in mature intact male rats are described in the present paper. It has been shown that each preparation, administered separately for 10 days, induced a moderate decrease in the weight of the ventral prostate (VP), anterior prostate lobe or coagulating gland (CG) and seminal vesicles (SV), in the DNA content and number of cells in the VP. 5 alpha-reductase activity was also decreased; the epithelium secretory activity of the VP was suppressed. After combined FI (10 mg/kg bw) and Hex (40 micrograms/kg bw) the following castration-like effects were observed: an abrupt fall in the weight of the accessory sexual glands, a decrease of DNA level and cell number in the VP as well as a suppression of the production of 5 alpha-reductase metabolites in this structure. Histologically, a marked degenerative changes in the VP secretory epithelium was observed; on the contrary an hyperplasia of connective and smooth muscle cells was evident. When FI alone was administered to rat, the above-mentioned changes were accompanied by a pronounced elevation of plasma bio-LH and testosterone (T) levels, also an increase of testicular delta 5-3 beta-hydroxysteroid dehydrogenase activity was observed. On the contrary, when Hex was administered alone or in combination with FI, bio-LH and T levels and enzyme activity decreased. We conclude that Hex administration in low doses, in combination with FI, could be an alternative method for a complete androgen blockade of the accessory sexual glands.