Partial purification and mechanism of action of gonadotrophin surge attenuating factor (GnSAF)
Gonadotrophin surge attenuating factor (GnSAF) is a non-steroidal ovarian factor which reduces pituitary responsiveness to GnRH both in vitro and in vivo. GnSAF is present in serum from superovulated women in a 141 kDa molecular weight form. GnSAF bioactivity (suppression of GnRH-induced LH secretion from cultured rat pituitary cells) in serum from superovulated women is not overcome by incubation with an inhibin antibody, demonstrating that it is distinct from inhibin. Under the culture conditions used, the ovarian steroids had no significant suppressive effects on GnRH-induced LH secretion, showing that GnSAF bioactivity is not due oestradiol or progesterone. GnSAF is also present in serum from the follicular phase of spontaneously cycling women with maximal levels being produced during the mid follicular phase. It has been suggested that GnSAF production during the follicular phase suppresses LH release from the pituitary until the levels of oestradiol produced by the developing follicle are high enough to overcome the effects of GnSAF and the LH surge occurs. However, suppression of LH secretion by an enriched GnSAF preparation is potentiated by oestradiol and progesterone, both individually and in combination. This suggests that it is not a rise in steroid positive feedback but a decrease in GnSAF negative feedback which enables the LH surge to occur. Follistatin and GnSAF in combination have additive effects on the suppression of GnRH-induced LH secretion, whereas GnSAF and inhibin in combination cause no greater suppression than they do individually. GnSAF present in inhibin-stripped human follicular fluid is also able to reduce both the GnRH self-priming response, and its augmentation by progesterone, by rat pituitary cells in culture after only 90 minutes exposure. Inhibin and follistatin have no such effects under the same conditions.