Neuroendocrine Mechanism Regulating Luteinizing Hormone Secretion during Periovulatory Period: Negative and Positive Feedback Actions of Estrogen in the Brain

Abstract

The brain mechanism governing pulsatile GnRH release, which induces pulsatile LH secretion from the pituitary, plays a key role to maintain the ovarian cyclicity. The frequency of GnRH/LH pulses is much higher at follicular phase than that at luteal phase. The increase in the pulse frequency is accepted to contribute to ovarian follicular development. Low level of estrogen secreted from immature follicles has a negative feedback effect on GnRH/LH release, while high level estrogen from matured follicles has a positive feedback effect on the release, resulting in the LH surge. One of the positive feedback action sites of estrogen has been revealed to be located in the medial preoptic area, where abundant estrogen receptors (ER) have been found. The arcuate nucleus, where many ERs is also distributed, could be another action site. It is suggested that GnRH pulse and surge generator are separately located and function in the brain, since multiple unit activity reflecting the GnRH pulse generator activity is not associated with the LH surge. Environmental factors, such as stress, malnutrition and suckling stimulus, suppress LH pulses, but not affect LH surge induced by exogenous estrogen treatment. This fact may be well explained by the above-mentioned concept that the mechanisms regulating LH pulse and surge modes of LH secretion are independent. The inhibition of LH surge and ovulation by the inhibitory environmental factors is due to the suppression the activity of GnRH pulse generator but not that of surge generator.