Immunoneutralization of Endogenous Inhibin Modifies Hormone Secretion and Ovulation Rate in the Rat*

Studies were conducted to determine the effects of inhibin immunoneutralization on gonadotropins and sex steroids secretion, as well as ovulation rate and the outcome of pregnancy in the rat. These changes were compared to the normal pattern of hormone release during the estrous cycle, as well as to the ovulatory and gestational history of control animals. Measurement of plasma inhibin levels with antibodies raised against the N-terminus part of the alpha-chain of the molecule indicated an increase in immunoreactive inhibin-alpha release during the afternoon of proestrus, followed by a marked decline after the primary gonadotropin surge. Removal of endogenous inhibin by the iv injection of anti-inhibin serum on diestrus-1 caused the expected rise in plasma FSH, but not LH values. FSH secretion remained elevated for approximately 28 h, then returned to baseline. While not altering vaginal cytology, the injection of the antiserum during diestrus-1 or -2, and to a lesser degree, during estrus, caused a marked increase in the number of tubal ova shed during the subsequent estrus. However, plasma estrogen and progesterone remained comparable at all times between control and treated animals. In female rats mated after inhibin immunoneutralization at diestrus-1, the increase in ovulation rate resulted in a significant increase in developing fetuses, but only ca. 40% of the pups survived. In order to assess whether elevated FSH secretion represented the primary mechanism through which removal of endogenous inhibin increased the number of maturing follicles, ovine FSH was infused for 35 h starting in diestrus-1 or diestrus-2. Similar to the treatment with the anti-inhibin serum, FSH infusion caused an increase the number of eggs present in the oviducts on the next day of estrus. These results support the existence of a close functional relationship between the circulating levels of FSH and inhibin in the female rat. They also indicate that immunization against inhibin increases ovulation rate, a phenomenon probably mediated through elevated levels of circulating FSH.