NEUROENDOCRINE CONTROL OF REPRODUCTION.
The hypothalamic GnRH, the ovarian steroids estradiol and progesterone, and less well-characterized ovarian peptide hormones, are the three factors involved in modulating gonadotropin function. The GnRH, released in a pulsatile manner, plays a pivotal role in the induction of pituitary secretion of LH. Normal gonadotropin secretion is dependent on pulsatile GnRH discharge with a frequency and amplitude within a critical range. The LH pulses frequencies of 1/90 minutes (follicular phase) to 1/220 minutes (late luteal phase) have been measured and are thought to represent the GnRH frequency at the corresponding phase of the cycle. Decreasing GnRH pulse frequency decreases LH secretion but increases FSH secretion; this situation may be remedied by the administration of exogenous pulsatile GnRH. Increased GnRH pulse frequency has been one of the factors said to be responsible for hyper secretion of LH in patients. Glucocorticoids also have been shown to have a differential effect on FSH and LH secretion, whereby they suppressed LH responsiveness to GnRH but did not have the same effects on FSH secretion. Glucocorticoid levels may prove to be part of the mechanism of differential control of FSH and LH secretion.
Pulsatile release of GnRH is mediated by a catecholaminergic mechanism and can be modified itself by gonadal steroids, as well as endorphins and possibly leukotrienes and cytokines. Dopaminergic neurons also have an inhibitory effect on GnRH pulsatility via an effect on the arcuate nucleus. The net effect of the various neurotransmitter-brain peptides is to dictate the pulsatility of GnRH via interaction with hypothalamic centers. The GnRH pulsatility plays a permissive role in pituitary gonadotropin synthesis and secretion, but the major control elements regulating gonadotropin levels are controlled by ovarian steroid feedback on the anterior pituitary.