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 re lease:(1) NPY release in the S-ME was pulsatile; (2) NPY pulses occurr ed 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-re sponsive manner; whereas (4) infusion of a specific antiserum to NPY i nto the S-ME suppressed LHRH pulses. Further studies suggest that NPY neurons may mediate the action of steroid hormones. While treatment wi th a small dose of estrogen did not affect the coupling of NPY and LHR H pulses, it enhanced the sensitivity of LHRH release in response to N PY by 10,000-fold. Progesterone treatment 24 hr after estrogen induced an increase in LHRH release followed by an LH surge: Progesterone inc reased the pulse frequencies of both NPY release and LHRH release, mai ntaining the tight coupling of the pulses, while increasing LHRH pulse amplitude, but not NPY pulse amplitude. A parallel role of norepineph rine (NE) neurons in the modulation of pulsatile LHRH release was also observed indicating that more than one neuronal system can be simulta neously involved in the regulation of LHRH release and the action of o varian steroids. Moreover, in the modulation of LHRH pulses, NPY and N E neurons were independent of each other. Further studies indicate tha t the LHRH neurosecretory system in the sexually immature monkey was i nsensitive to estrogen. This insensitivity appeared to be due to the t onic inhibition of pulsatile LHRH release by gamma-aminobutyric acid ( GABA) neurons through GABA(A) receptors. These results suggest that in vivo LHRH release is modulated by NPY, NE, and GABA neuronal inputs w hich mediate the action of steroid hormones. (C) 1994 Academic Press, Inc.