The role of changing pulse frequency in the regulation of ovulation

Ovulatory cycles in women result from sequential stimulation of ovarian follicular development by pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH). In the follicular phase the initial FSH stimulus declines and LH secretion increases toward the mid-cycle ovulatory surge. During the luteal phase gonadotrophin secretion is reduced. This reflects the effects of ovarian steroids inhibiting the frequency of gonadotrophin releasing hormone (GnRH) secretion by the hypothalamus, and the direct effects of oestradiol and inhibin to reduce gonadotroph (FSH) secretion. The frequency of GnRH stimulation of the gonadotroph is a selective regulator of gonadotrophin synthesis, with slow frequency stimuli favouring FSH and faster frequency stimuli favouring LH secretion. Current research has only revealed a single gonadotrophin releasing hormone. Thus, the ability to change the pattern (particularly frequency) of GnRH stimulation of the gonadotroph is proposed as an important regulator of differential FSH and LH synthesis, and hence of ovulatory cycles. In some disorders of ovulation the ability to regulate GnRH pulse frequency appears to have been lost. Slow frequency GnRH pulses are consistently seen in women with hypothalamic amenorrhoea and hyperprolactinaemia. The reduced GnRH secretion appears to reflect increased hypothalamic opiate tone and can be rapidly reversed with an opiate receptor blocker. Other disorders associated with anovulation show rapid frequency GnRH secretion, and polycystic ovarian syndrome (PCO) is commonly associated with fast-frequency, high-amplitude LH (GnRH) pulses. Such a GnRH stimulus would favour LH and androgen production and the failure of ovarian follicular maturation in PCO may reflect inappropriate sequential FSH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)