Inhibitory Effects of Porcine Follicular Fluid on Monkey Serum FSH Levels and Follicular Maturation1

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Abstract
To examine the role of FSH during follicular maturation in monkeys, serum FSH was suppressed during cycles on days 1-4 i.p. by administration of charcoal-treated porcine follicular fluid (PFF1, crude inhibin-F). Following PFF1 treatment, the putative dominant follicle was examined on days 10-14. Granulosa cells were recovered from this follicle and cultured. Treatment of 4 monkeys with PFF1 led to decreased size of the dominant follicle and a decrease in the number of granulosa cells recovered from the follicle. Serum FSH, but not LH [lutropin], levels were decreased 50-80% in 3 of 4 monkeys. Pig serum (control) had no discernible effects. The actions of charcoal-treated PFF1 were examined further in long-term castrate female cynomolgus and rhesus monkeys. With a single injection of 0.5, 1.0, 5, 10, 15 or 100 ml of PFF PFF1 administration at time 0, there was a dose-dependent decrease in FSH, with no significant alteration in serum LH. With the lowest dose (5.0 ml), there was a 25% decrease (P < 0.05) in serum FSH after 42 h. Both 30 and 100 ml doses produced a near maximal decrease (70-80%) in serum FSH. There may be 2 pools of FSH, one of which is not suppressible by PFF1, or a single pool which is not completely suppressible by this experimental approach. Additional experiments were performed in monkeys to examine the effect of PFF1 administered during the spontaneous midcycle and exogenous estrogen-induced FSH/LH surges. PFF1 was injected into 2-4 daily doses of 4 ml each during the anticipated time of the midcycle gonadotropin surges. These 4 day PFF1 treatments led to postponement of the LH/FSH surges in 2 monkeys and the abolishment of the anticipated LH/FSH surges in 2 additional monkeys. These four PFF1-treated monkeys failed to ovulate in the treated cycle, but did ovulate during the next menstrual cycle. Administration of porcine serum at midcycle did not alter the midcycle LH/FSH surge. Administration of a daily 10 ml dose of PFF1 over a 4 day period inhibited the estrogen-induced (estradiol benzoate) rise of LH and FSH in 5 intact adult female cynomolgus and rhesus monkeys during the early follicular phase. In a final experiment, s.c. administration of 2 ml PFF1, but not pig serum, to both male and female infant (12-17 mo.) rhesus monkeys led to a selective decline in serum FSH.