CIRCULATING GONADOTROPIN SURGE-ATTENUATING FACTOR FROM SUPEROVULATED WOMEN SUPPRESSES IN-VITRO GONADOTROPIN-RELEASING-HORMONE SELF-PRIMING

A perifusion system based on ovine pituitary tissue explants was used to investigate the effects of follicular fluid (hFF) and serum from su perovulated women on pituitary responsiveness to gonadotrophin-releasi ng hormone (GnRH). The specific aims of the study were to determine bo th if gonadotrophin surge-attenuating factor (GnSAF) bioactivity is pr esent in the peripheral circulation as well as in the follicles of sup erovulated women and if GnSAF suppresses GnRH self-priming in vitro. T wo pulses of GnRH, 1 h apart, produced marked peaks in LH secreted fro m control chambers, with GnRH self-priming evident in the significant difference between the first (134.4 +/- 1.7-232.1 +/- 24.0% of basal s ecretion) and second (183.9 +/- 15.8-313.9 +/- 14.0% of basal secretio n) LH peaks. Both follicular fluid and serum pooled from two different groups of women produced marked suppression of the first (unprimed) a nd second (primed) LH peaks. The hFF reduced the first LH peak to 69.6 +/- 7.8 and 60.2 +/- 9.7% and the second LH peak to 57.4 +/- 6.7 and 42.6 +/- 6.5% of control LH secretion. Overall, the serum reduced the first and second LH peaks to 76.8 +/- 4.2 and 62.9 +/- 3.6% of control respectively. These results demonstrated that GnSAF bioactivity suppr esses GnRH self-priming, and is present in both the peripheral circula tion and hFF. The same material administered to dispersed ovine pituit ary monolayers produced similar marked suppression of GnRH-induced LH secretion, with approximately 50-fold less GnSAF bioactivity in serum compared with hFF. Combined doses of oestradiol and progesterone, or h FF from large follicles containing little GnSAF, produced stimulation of GnRH-induced LH secretion and GnRH self-priming (second peaks 78.1 +/- 38.9 and 27.4 +/- 15.7% respectively higher than first peaks). Thu s, in conclusion, GnSAF in hFF and serum markedly attenuated both unpr imed and primed pituitary response to GnRH, virtually abolishing the G nRH self-priming effect.