The control of gonadotrophin secretion by ovarian steroids

Ovarian steroids exert feedback effects at the level of both the hypothalamus and anterior pituitary to regulate the secretion of gonadotrophins. Oestradiol decreases the activity of mRNA encoding the alpha and beta subunits of gonadotrophins. In the late follicular phase, oestradiol exerts a positive feedback control over pituitary luteinizing hormone (LH) release and a negative control over follicle stimulating hormone (FSH). Oestradiol also induces a pre-ovulatory increase of gonadotrophin releasing hormone (GnRH) secretion which is continuous rather than episodic. Such a GnRH rise may not be required to produce the LH surge. Progesterone exerts its major effect at the hypothalamic level and decreases GnRH pulse frequency by inducing the release of beta-endorphin. However, the hypothalamus is not the exclusive target of progesterone action, for its facilitatory action on gonadotrophin release may be at the level of the pituitary gland. This positive feedback effect was studied in women with hypothalamic gonadotrophin deficiency treated with pulsatile GnRH. In physiological doses, progesterone had a stimulatory effect on LH secretion at the pituitary level. Finally, regarding the effect of androgens upon gonadotrophin secretion, the administration of a non-steroidal pure anti-androgen (Flutamide) for 12 months in 10 normally cycling women did not change significantly the mean levels, frequency, or amplitude of LH pulses or the LH and FSH responsiveness to GnRH. Androgens (apart from their aromatization to oestrogens) do not directly play a physiological role in gonadotrophin regulation in normal women.