IMMUNOLOGICAL AND BIOLOGICAL-ACTIVITIES OF PITUITARY FSH ISOFORMS IN PREPUBERTAL MALE-RATS - EFFECT OF ANTIANDROGENS

In male rats androgens are involved in the regulation of follicle-stim ulating hormone (FSH) synthesis and secretion. Two nonsteroidal antian drogens, flutamide and Casodex, were used to study the influence of an drogens on the carbohydrate structure of FSH isoforms and the relation ship with their bioactivity in prepubertal male rats. Different doses of flutamide or Casodex (vehicle, 1, 5, or 10 mg/rat/day) were adminis tered subcutaneously for 10 days to 23-day-old rats. Immunological FSH was determined by radioimmunoassay and the bioactivity by in vitro Se rtoli cell bioassay. Concanavalin A affinity chromatography was used t o study the distribution of immunoactive and bioactive pituitary FSH i soforms. A significant depletion of immunological and biological pitui tary FSH contents was observed even at the lowest dose of flutamide or Casodex used. The bioactive/immunoactive ratio of pituitary FSH was r educed at the highest dose of flutamide; however, no change was observ ed in Casodex-treated rats, suggesting a differential effect of the an tiandrogens on the FSH bioactivity. Flutamide treatment provoked a sig nificant decrease in proportion and bioactivity of FSH isoforms bearin g biantennary and truncated hybrid oligosaccharide side chains and an increase in the proportion but a decrease in bioactivity of FSH isofor ms bearing high-mannose oligosaccharides. Conversely, Casodex administ ration did not modify the proportions of FSH isoforms, although those bearing biantennary and truncated hybrid structures were less bioactiv e, while those bearing high-mannose oligosaccharides were more bioacti ve. The highest dose of flutamide decreased the bioactive/immunoactive ratio of FSH isoforms with a high degree of branching in their carboh ydrate chains. Our results suggest that androgens, acting directly and indirectly at the pituitary, regulate the selective incorporation of sugar residues to the FSH molecule, thus modulating its biological act ivity.