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neurons projecting from the locus ceruleus [
64
], the BNST [
41
], and the amygdala [
45
],
as well as several neuropeptides, including AVP, Dyn, and calcitonin gene-related pep-
tide (CGRP), along with the chiefl y inhibitory amino acid neurotransmitter
γ
-aminobutyric acid (GABA), have all been shown to play key roles in the stress-induced
suppression of reproductive function. These mechanisms are further discussed below.
Finally, while stress is commonly known to confer an energetic advantage to an organ-
ism at the expense of its nonessential bodily functions, e.g., reproduction, in some sce-
narios, stressful stimuli may serve to enhance the functions of the HPG axis and, in
particular, induce premature LH surges and ovulation [
91
,
92
]. These observations hint
at a complex network of stress-reactive neurons spanning numerous regions of the brain,
without a clearly identifi ed central mediator of the integration of stress stimuli with
reproductive function, in the context of kisspeptin signaling.
To date, various limbic structures have been differentially implicated in the modu-
lation of the effects of different stressors on the HPA axis [
8
]. We have recently shown
evidence for the involvement of the MeA and CeA in psychogenic and immunological
stress-induced suppression of the GnRH pulse generator, respectively [
45
]. Adult
female rats in which the MeA was chemically lessoned showed an attenuated restraint-
induced, but
not
hypoglycemia- or LPS-induced, decrease in LH pulse frequency
[
45
]. The extent of the LPS-induced suppression of pulsatile LH secretion was
strongly reduced in CeA-lesioned animals vs. intact controls, though the CeA lesions
had
no
effect on the LH pulse following restraint or hypoglycemic stress [
45
]. These
data suggest that these two amygdaloid loci are not involved in mediating the hypo-
glycemic stress-induced suppression of the LH pulse. Indeed, we have previously
shown that removal of the area postrema of the caudal brainstem prevents insulin-
induced glucoprivic suppression of pulsatile LH secretion [
93
].
CRF neurons of the BNST connect the PVN with the amygdala, hippocampus,
and prefrontal cortex [
94
]. Further, non-CRF interneurons project to mPOA GnRH
perikarya [
95
]. When stimulated electrochemically, lateral BNST neurons prevent
ovulation by abrogating the preovulatory surge of LH, while medial BNST neurons
advanced the LH surge in proestrus rats [
96
]. Administration of CRF directly into
the dorsolateral BNST of adult female rats dose dependently suppresses pulsatile
LH secretion and activates GABA neurons in the mPOA [
41
]. Furthermore, intra-
BNST injection of a selective CRF-R2 antagonist blocked the restraint-induced, but
not IIH-induced, suppression of pulsatile LH secretion [
41
].
The brainstem noradrenergic locus ceruleus is innervated by CRF neurons pro-
jecting from CeA [
97
], BNST [
98
], and PVN [
99
]. Bilateral electrolytic lesions of
the locus ceruleus disrupt both the pulsatile [
100
] and surge [
101
] modes of LH
release. Intra-cerulear administration of CRF to adult OVX rats dose dependently
suppresses pulsatile LH secretion and activates GABA neurons in the mPOA [
64
].
These effects are amplifi ed by estradiol [
64
]. Furthermore, intra-cerulear injection
of a nonselective CRF receptor antagonist blocked the restraint-induced, but not
glucoprivic, suppression of pulsatile LH secretion [
64
].
Although CRF signaling appears indispensible in mediating stress-induced sup-
pression of the HPG axis, other neuropeptide and amino acid signaling molecules
have also been implicated in the inhibition of GnRH neurons. AVP and CRF, both
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