Immunological and Biological Activities of Pituitary FSH Isoforms in Prepubertal Male Rats: Effect of Antiandrogens

Abstract

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.

Androgen Regulation of Immunological and Biological Activities of Pituitary Follicle-Stimulating Hormone Isoforms inMale Rats

“…The same pattern is observed in intact 10-day-old rats. Similar changes were obtained in a previous study where androgen action in prepubertal rats was blocked by flutamide administration [10]. …”

“…Also, it has been demonstrated that castration as well as antiandrogen administration increase the proportion of some of the less acidic isoforms [8, 9]. In our previous report we have shown that antiandrogen administration to prepubertal male rats altered both the biological activity and the distribution profile of pituitary FSH isoforms when determined according to their oligosaccharide structure within the terminal sugar, sialic acid [10]. These results suggest that the endocrine milieu not only regulates sialic acid content of FSH isoforms but the processing of their inner oligosaccharide structure as well.…”

Effect of Dihydrotestosterone on Pituitary Follicle-Stimulating Hormone Isoforms in Adult Male Rats Treated with a Gonadotropin-Releasing Hormone Antagonist

“…In normal women, previous studies have demonstrated that the endocrine milieu modulates not only the incorporation of the terminal sialic acid to the carbohydrate chain but also the processing of the inner structure of FSH oligosaccharides [17]. In immature male rats, we demonstrated that either castration or antiandrogen treatment induces an increase in the proportion of pituitary FSH isoforms bearing incompletely processed carbohydrate chains, whereas androgens appear to reverse this situation [26, 27]. However, the mechanism by which androgens may be influencing the carbohydrate synthesis of FSH in the adult pituitary is not clearly elucidated.…”

“…T or DHT (0.25 mg/rat in corn oil) were injected subcutaneously (s.c.) every day. F was administered s.c. twice a day (5 mg/day/rat as a suspension in a 0.9% NaCl solution containing 1% gelatin; [26]). GnRH Ant was injected daily (1 mg/kg/day in saline [28]).…”

Effects of Androgens and Antiandrogens on the Quantitative Immunohistochemistry of Gonadotrope Cells in Prepubertal Male Rats

“…The specific androgen-receptor blockade caused by the nonsteroidal antiandrogens, flutamide and Casodex, has likewise proved to be a valid tool for the study of the in vivo effects of androgens [6, 7]. Flutamide blocks androgen receptors either at peripheral sites or at the hypothalamic-pituitary axis, thus preventing the feedback regulation of androgens on gonadotropin synthesis and secretion [8, 9].…”