Hypothalamic dysfunction

A pulsatile GnRH stimulus is required to maintain gonadotropin synthesis an d secretion. The frequency and amplitude of GnRH pulses determine gonadotro pin subunit gene expression and secretion of pituitary LH and FSH. Rapid fr equency (more than 1 pulse per h) GnRH pulses favor LH while slower frequen cies favor FSH secretion. During ovulatory cycles, an increase in GnRH freq uency during the follicular phase favors LH synthesis prior to the LH surge , while following ovulation, luteal steroids slow GnRH pulses to favor FSH synthesis. Thus, a changing frequency of GnRH stimulation of the gonadotrop e is one of the mechanisms involved in differential gonadotropin secretion during ovulatory cycles. In hypothalamic amenorrhea a majority of women exh ibit a persistent slow frequency of LH (GnRH) pulses., which reflects exces s hypothalamic opioid tone and can be temporarily reversed by opioid antago nists. At the other end of the spectrum, in polycystic ovarian syndrome, LH (GnRH) pulses are persistently rapid and favor LH synthesis, hyperandrogen ism and impaired follicular maturation. Administration of progesterone can slow GnRH pulse secretion. favor FSH secretion and induce follicular matura tion. Thus, the ability to change the pattern of GnRH secretion is an impor tant factor in the maintenance of cyclic ovulation, and loss of this functi on leads to anovulation and amenorrhea. (C) 2001 Published by Elsevier Scie nce Ireland Ltd.