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Fig. 20.4
Effects of restraint, insulin-induced hypoglycemia (IIH), and lipopolysaccharide (LPS)
stress on kisspeptin (
Kiss1
) mRNA expression in the medial preoptic area (mPOA) (
a
) and arcuate
nucleus (ARC) (
b
), and on kisspeptin receptor (
Kiss1r
) mRNA expression in the mPOA (
c
) and
ARC (
d
) in ovariectomized estradiol (E
2
)-replaced rats.
Kiss1
and
Kiss1r
mRNA levels were mea-
sured in brain micropunch samples from the mPOA or ARC using real-time RT-PCR. Quantifi cation
for
Kiss1
,
Kiss1r,
and 28S rRNA was carried out on all samples and the values are expressed as a
ratio of
Kiss1
mRNA and 28S rRNA, or
Kiss1r
mRNA and 28S rRNA (mean ± SEM). *
P
< 0.05 vs.
respective control.
#
P
< 0.05 vs. restraint or LPS controls;
n
= 8 per group (from Kinsey-Jones JS,
Li XF, Knox AM, Wilkinson ES, Zhu XL, Chaudhary AA, et al. Down-regulation of hypothalamic
kisspeptin and its receptor, Kiss1r, mRNA expression is associated with stress-induced suppres-
sion of luteinising hormone secretion in the female rat. J Neuroendocrinol. 2009 Jan;21(1):20-9.
Reprinted with permission from John Wiley & Sons)
adulthood, and thus preventing infl ammatory suppression of LH secretion [
59
].
Indeed, the HPA axis is differentially modulated by the male and female gonadal
steroids: hypothalamic activation of ER
augments the diurnal and stress-induced
rises in circulating CORT, thus impairing glucocorticoid negative feedback on the
HPA axis [
60
], while T enhances this feedback mechanism by increasing the avail-
ability of bioactive CORT, thereby decreasing circulating glucocorticoid levels [
61
].
In summary, neonatal LPS challenge modulates kisspeptin/Kiss1r signaling in
adults and differentially programs responsiveness to stress later in adulthood in
males and females.
Intravenous administration of insulin dramatically decreases plasma glucose,
inducing acute hypoglycemia—a well-established paradigm of metabolic stress.
Such stress rapidly elevates serum cortisol and suppresses both the endocrine and
the electrophysiological correlates of the GnRH pulse generator in ovariectomized
α
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