Ovarian feedback, mechanism of action and possible clinical implications

The secretion of gonadotrophins from the pituitary in women is under ovarian control via negative and positive feed-back mechanisms. Steroidal and non-steroidal substances mediate the ovarian effects on the hypothalamic-pituitary system. During the follicular phase of the cycle, estradiol (E2) plays a key role, while circulating progesterone (at low concentrations) and inhibin B contribute to the control of LH and FSH secretion respectively. During the luteal phase, both E2 and progesterone regulate secretion of the two gonadotrophins, while inhibin A plays a role in FSH secretion. The intercycle rise of FSH is related to changes in the levels of the steroidal and non-steroidal substances during the luteal-follicular transition. In terms of the positive feedback mechanism, E2 is the main component sensi-tizing the pituitary to GnRH. Activity of a non-steroidal ovarian substance, named gonadotrophin surge-attenuating factor (GnSAF), has been detected after ovarian stimulation. It is hypothesized that GnSAF, by antagonizing the sen-sitizing effect of E2 on the pituitary, regulates the amplitude of the endogenous LH surge at midcycle. Disturbances in the feedback mechanisms can occur in various abnormal conditions or after treatment with pharmaceutical com-pounds that interfere with the production or the action of endogenous hormones. Key words: FSH/LH/estrogen/ovarian feedback/progesteron