Je. Levine et al., AMPLITUDE AND FREQUENCY-MODULATION OF PULSATILE LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE, Cellular and molecular neurobiology, 15(1), 1995, pp. 117-139
1. A variety of neuroendocrine approaches has been used to characteriz
e cellular mechanisms governing luteinizing hormone-releasing hormone
(LHRH) pulse generation. We review recent in vivo microdialysis, in vi
tro superfusion, and in situ hybridization experiments in which we tes
ted the hypothesis that the amplitude and frequency of LHRH pulses are
subject to independent regulation via distinct and identifiable cellu
lar pathways. 2. Augmentation of LHRH pulse amplitude is proposed as a
central feature of preovulatory LHRH surges, Three mechanisms are des
cribed which may contribute to this increase in LHRH pulse amplitude:
(a) increased LHRH gene expression, (b) augmentation of facilitatory n
eurotransmission, and (c) increased responsiveness of LHRH neurons to
afferent synaptic signals, Neuropeptide Y (NPY) is examined as a proto
typical afferent transmitter regulating the generation of LHRH surges
through the latter two mechanisms. 3. Retardation of LHRH pulse genera
tor frequency is postulated to mediate negative feedback actions of go
nadal hormones, Evidence supporting this hypothesis is reviewed, inclu
ding results of in vivo monitoring experiments in which LHRH pulse fre
quency, but not amplitude, is shown to be increased following castrati
on. A role for noradrenergic neurons as intervening targets of gonadal
hormone negative feedback actions is discussed. 4. Future directions
for study of the LHRH pulse generator are suggested.