Steroid modulation of pulsatile LHRH release in the rhesus monkey.

Studies using push-pull perfusion of the stalk-median eminence (S-ME) in ovariectomized adult monkeys indicate that input of neuropeptide Y (NPY) neurons is an important modulator for the pulsatility of LHRH release: (1) NPY release in the S-ME was pulsatile; (2) NPY pulses occurred coupled to LHRH pulses, with NPY pulses preceding LHRH pulses; and (3) infusion of NPY into the S-ME stimulated LHRH release in a dose-responsive manner; whereas (4) infusion of a specific antiserum to NPY into the S-ME suppressed LHRH pulses. Further studies suggest that NPY neurons may mediate the action of steroid hormones. While treatment with a small dose of estrogen did not affect the coupling of NPY and LHRH pulses, it enhanced the sensitivity of LHRH release in response to NPY by 10,000-fold. Progesterone treatment 24 hr after estrogen induced an increase in LHRH release followed by an LH surge: Progesterone increased the pulse frequencies of both NPY release and LHRH release, maintaining the tight coupling of the pulses, while increasing LHRH pulse amplitude, but not NPY pulse amplitude. A parallel role of norepinephrine (NE) neurons in the modulation of pulsatile LHRH release was also observed indicating that more than one neuronal system can be simultaneously involved in the regulation of LHRH release and the action of ovarian steroids. Moreover, in the modulation of LHRH pulses, NPY and NE neurons were independent of each other. Further studies indicate that the LHRH neurosecretory system in the sexually immature monkey was insensitive to estrogen. This insensitivity appeared to be due to the tonic inhibition of pulsatile LHRH release by gamma-aminobutyric acid (GABA) neurons through GABAA receptors. These results suggest that in vivo LHRH release is modulated by NPY, NE, and GABA neuronal inputs which mediate the action of steroid hormones.