Neural control of the synthesis and release of luteinizing hormone-releasing hormone.

Abstract

Preovulatory surges of luteinizing hormone (LH) depend upon neurotransmitter activation of neurons that secrete LH-releasing hormone (LHRH, gonadotropin-releasing hormone GnRH) and noradrenaline plays a pivotal role in this critical event. The interaction is amongst noradrenaline and other neurotransmitters such as GABA (gamma-aminobutyric acid), opiates, serotonin and excitatory amino acids (N-methyl-D-aspartate, NMDA) on LHRH neuronal activity are complex. GABA and opiates suppress the presynaptic release of noradrenaline but only GABA also directly affects the responsiveness of LHRH neurons to noradrenaline. Morphine induces the release of serotonin which either directly or indirectly via other neurotransmitters (e.g. dopamine) sensitizes LHRH neurons to the stimulatory effects of noradrenaline. NMDA rapidly induces LH release but whether this drug directly affects the activity of LHRH neurons is not known. The neuronal release of LHRH is modulated by the action of oestrogen on these various neurotransmitter systems. Antioestrogens, when placed into the medial preoptic area of otherwise completely oestrogenized rats, block LH surges; LHRH mRNA levels in such animals resemble those in 9-day castrated rats. Normally, LHRH message levels increase about the time of increased noradrenaline secretion just before the LH surge. NMDA rapidly releases LH and LHRH mRNA levels are significantly raised within 15 minutes and remain so over the next 45 minutes. Thus, it seems that stimuli which evoke LHRH release also increase LHRH mRNA transcription to replenish the hormone released during the LH surge.