MICROHETEROGENEITY OF PITUITARY FOLLICLE-STIMULATING-HORMONE IN MALE-RATS - DIFFERENTIAL-EFFECTS OF THE CHRONIC ANDROGEN DEPRIVATION INDUCED BY CASTRATION OR ANDROGEN BLOCKADE

Testicular androgens are known to influence not only the secretion but also the bioactivity and molecular composition of pituitary FSH. In the present study, we investigated the effects of chronic androgen blockade and castration on the molecular heterogeneity of the gonadotrophin. Groups of male adult rats (five animals per group) received one of the following treatments: vehicle, the non-steroidal anti-androgens casodex (20 mg/kg per day) or flutamide (20 mg/kg per day), or castration. After 8 weeks, the animals were killed and individual pituitary homogenates fractionated by isoelectric focusing (IEF) on sucrose density gradients in the pH range 2-5-8. FSH was measured by radioimmunoassay (RIA) in the individual fractions and by in-vitro bioassay (Sertoli cell aromatase bioassay) in pools of fractions which were combined according to pH intervals of 0.5 units. Bioactive and immunoreactive FSH were also measured in sera and unfractionated pituitary extracts. Testosterone and inhibin were assayed in sera by RIA. A significant increase in serum immunoreactive and bioactive FSH was demonstrated in flutamide-treated and castrated animals, whereas the pituitary content of bioactive FSH remained unchanged in the four groups. Serum testosterone and inhibin were undetectable in castrated animals and significantly increased in those treated with flutamide. By RIA, the IEF profiles of the flutamide-treated and castrated rats showed a significant reduction of the FSH isoforms with 3.5<pI<4, with a significant increase in the isoforms with pI>4 only in the castrated group. By bioassay, there was a significant decrease in the isoforms with 3.5<pI<4 in both casodex- and flutamide-treated animals, with no significant differences between the two groups. Castration caused a further significant shift in the relative distribution of FSH isoforms towards the less acidic components, with a significant increase in the isoforms with 5<pI<5.5 not attained by androgen blockade alone. These results suggest that the effects of long-lasting castration on pituitary FSH heterogeneity cannot be entirely reproduced by the androgen blockade. Since inhibin, eliminated by castration but not by androgen blockade, is a major regulator of FSH in the male rat, we speculate that it might not only influence FSH secretion but also modulate its qualitative properties.