Passive immunoneutralization of endogenous inhibin: sex-related differences in the role of inhibin during development.

The purpose of these studies was to ascertain the extent to which endogenous inhibin regulates follicle-stimulating hormone (FSH) secretion at different intervals during development in the male and female rat. This was determined by examining the changes in plasma FSH that resulted from immunoneutralizing endogenous inhibin in male and female rats at different ages during development and into adulthood. Passive immunoneutralization of endogenous inhibin was achieved using specific, high titer ovine antiserum, generated against the alpha-subunit of the recently described inhibin molecule. Optimal antiserum volumes and time after injection required to observe maximal changes in FSH secretion were determined in initial experiments. No clear effect of immunoneutralizing endogenous inhibin could be demonstrated on FSH secretion in female rats until 20 days of age, after the completion of the endogenous rise in FSH which occurs between days 5 and 20. Thereafter, injection of the anti-alpha-inhibin serum (anti-alpha IN) produced a progressively marked increase in plasma FSH as the age of the females increased. In male rats, injection of the anti-alpha IN serum caused an increase in FSH secretion as early as 5 days of age, although the response was more delayed at this age than at later times. The ability of the anti-alpha IN serum to increase plasma FSH was observed through 20 days of age. At 30 days of age, during the peak of the endogenous rise in plasma FSH, injection of the anti-alpha IN serum failed to further increase the already elevated levels of plasma FSH. As the endogenously high levels of FSH gradually decreased, the ability of anti-alpha IN serum to increase FSH secretion returned (40 days of age) but was diminished by 50 days of age and was completely lost by 60 days of age. The results of the present study indicate that inhibin plays an increasingly important role as a regulator of FSH secretion in the female from at least 20 days of age into adulthood. In the male, however, the role of inhibin in regulating FSH secretion, which is clearly present during early postnatal development, is apparently lost at the time of puberty.