Antisera to Porcine Follicular Fluid in Monkeys:Neutralization of Human and Pig Inhibin Activity in Vivo andin Vitro*

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Abstract
Repetitious administration of charcoal-stripped porcine follicular fluid (pFF) to four intact cycling females and six long term castrate rhesus monkeys was associated with a gradual onset of resistence to the FSH-suppressing effects of pFF. After a treatment hiatus of 6 or more months, the pFFinduced selective suppression of FSH in circulation was again demonstrable, but only transiently; that is, within 10–14 weeks after the resumption of therapy, even large doses of pFF were no longer effective in reducing serum FSH in these monkeys. One monkey was studied through seven regimens over 4 yr. Accordingly, our series of investigations was divided into three parts. First, we observed that these changing FSH patterns were apparently due to cyclic fluctuations of pFF antibodies in conjunction with the intermittent schedule of pFF administration. The amnestic response to booster injections occurred within 7–14 days, followed by a gradual decline in the anti-pFF titer during succeeding months. Second, we tested whether these anti-pFF sera would neutralize inhibin activities (selective FSH suppression) in rat pituitary cell cultures. Indeed, the anti-pFF sera were effective in blocking the FSH-suppressing activity of pFF. Again, each successive episode of pFF administration was correlated with an enhancement of the anti-pFF titer, indicated by greater potency of the monkey antisera in the in vitro setting. Thirdly, we assessed whether the monkey's anti-pFF sera would neutralize the inhibin activity in human FF (hFF); thereby establishing cross-reactivity with human inhibin. Clearly, the mixture of anti-pFF serum along with charcoal-stripped hFF prevented the selective suppression of FSH secretion that occurred when control monkey serum was used instead. These findings indicate that porcine inhibin present in charcoalstripped pFF is highly immunogenic in monkeys; further, some of the antibodies generated cross-react with the active inhibin component in hFF. Indeed, the neutralization of inhibin activity in hFF by anti-pFF monkey sera suggests some significant structural similarities between human and pig inhibins; yet, concurrently, the ready immunogenicity of pFF administered to monkeys indicates clear recognition of the antigen as an intrinsically foreign protein. These anti-pFF monkey sera may be useful in the establishment of RIA for porcine and/or human inhibins as well as the preparation of improved reagents for studying the physiological significance of this substance (s) in follicular fluid and circulation.