CONTROL OF LUTEINIZING-HORMONE-RELEASING HORMONE PULSE GENERATION IN NONHUMAN-PRIMATES

1. The pulsatile release of luteinizing hormone-releasing hormone (LHR H) is critical for reproductive function, However, the exact mechanism of LHRH pulse generation is unclear. The purpose of this article is t o review the current knowledge on LHRH pulse generation and to discuss a series of studies in our laboratory. 2. Using push-pull perfusion i n the stalk-median eminence of the rhesus monkey several important fac ts have been revealed. There is evidence indicating that LHRH neurons themselves have endogenous pulse-generating mechanisms but that the pu lsatility of LHRH release is also modulated by input from neuropeptide Y (NPY) and norepinephrine (NE) neurons. The release of NPY and NE is pulsatile, with their pulses preceding or occurring simultaneously wi th LHRH pulses, and the neuroligands NPY and NE and their agonists sti mulate LHRH pulses, while the antagonists of the ligands suppress LHRH pulses. 3. The pulsatile release of LHRH increases during the estroge n-induced LH surge as well as the progesterone-induced LH surge. These increases are partly due to the stimulatory effects of estrogen and p rogesterone on NPY neurons. 4. An increase in pulsatile LHRH release o ccurs at the onset of puberty. This pubertal increase in LHRH release appears to be due to the removal of tonic inhibition from gamma aminob utyric acid (GABA) neurons and a subsequent increase in the inputs of NPY and NE neurons to LHRH neurons. 5. There are indications that addi tional neuromodulators are involved in the control of the LHRH pulse g eneration and that glia may play a role in coordinating pulses of the release of LHRH and neuromodulators. 6. It is concluded that the mecha nism generating LHRH pulses appears to comprise highly complex cellula r elements in the hypothalamus. The study of neuronal and nonneuronal elements of LHRH pulse generation may serve as a model to study the os cillatory behavior of neurosecretion.