These results show that, in normal women, circulating FSH bioactivity is associated with isoforms with different oligosaccharide [correction of oligosacharide] structures according to hormonal status. FSH in the follicular phase has a higher degree of branching and a more complete carbohydrate chain than the FSH secreted during the menopause.
In male rats androgens are involved in the regulation of follicle-stimulating hormone (FSH) synthesis and secretion. Two nonsteroidal antiandrogens, fiutamide and Casodex, were used to study the influence of androgens on the carbohydrate structure of FSH isoforms and the relationship with their bioactivity in prepubertal male rats. Different doses of flutamide or Casodex (vehicle, 1, 5, or 10 mg/rat/day) were administered subcutaneously for 10 days to 23-day-old rats. Immunological FSH was determined by radioimmunoassay and the bioactivity by in vitro Sertoli cell bioassay. Concanavalin A affinity chromatography was used to study the distribution of immunoactive and bioactive pituitary FSH isoforms. A significant depletion of immunological and biological pituitary FSH contents was observed even at the lowest dose of flutamide or Casodex used. The bioactive/immunoactive ratio of pituitary FSH was reduced at the highest dose of flutamide; however, no change was observed in Casodex-treated rats, suggesting a differential effect of the antiandrogens on the FSH bioactivity. Flutamide treatment provoked a significant decrease in proportion and bioactivity of FSH isoforms bearing biantennary and truncated hybrid oligosaccharide side chains and an increase in the proportion but a decrease in bioactivity of FSH isoforms bearing high-mannose oligosaccharides. Conversely, Casodex administration did not modify the proportions of FSH isoforms, although those bearing biantennary and truncated hybrid structures were less bioactive, while those bearing high-mannose oligosaccharides were more bioactive. The highest dose of flutamide decreased the bioactive/immunoactive ratio of FSH isoforms with a high degree of branching in their carbohydrate 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 activity.
Follicle-stimulating hormone (FSH) is involved in the regulation and maintenance of gametogenesis. It exists in multiple molecular forms with different oligosaccharide structures which in turn are influenced by the hormonal milieu. Previous studies from our laboratory demonstrated that antiandrogen administration to immature male rats altered the biological activity and the distribution profile of pituitary FSH isoforms. The aim of this study was to examine possible modifications in pituitary FSH polymorphism throughout sexual development (10-, 32- and 75-day-old rats). In addition, the effect of androgen deprivation by castration (32-day-old rats) and its replacement with a nonaromatizable androgen – dihydrotestosterone – on pituitary FSH polymorphism was determined. Concanavalin A affinity chromatography was used to isolate groups of FSH isoforms according to their carbohydrate inner structure. Radioimmunoassay and Sertoli cell bioassay were used to evaluate FSH immuno- and bioactivities. Androgen rise in serum was accompanied by a marked increase in pituitary bio- and immuno-FSH content in 32- and 75-day-old rats. However, FSH pituitary content did not vary despite the significant increment observed in serum FSH levels after castration and decrease to control levels after androgen replacement. The distribution profile of immuno- and bioactive FSH changed throughout sexual maturation. The proportion of pituitary FSH isoforms bearing complex oligosaccharide structures (triantennary, bisecting, complete and truncated biantennary) increased with age, with a concomitant decrease in the proportion of isoforms bearing incomplete carbohydrate chains. The distribution profile observed in castrated 32-day-old rats was similar to that determined in 10-day-old animals. Androgen replacement restored the distribution profile to normal. These results suggest that androgens regulate the incorporation of sugar residues to the carbohydrate chains of pituitary FSH favoring the biosynthesis of complex-type oligosaccharide structures.
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