Neurokinin B signaling in the female rat : a novel link between stress and reproduction
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Date
Authors
Grachev, Pasha
Li, X.F.
Hu, M.H.
Li, S.Y.
Millar, Robert P.
Lightman, Stafford L.
O'Byrne, Kevin T.
Journal Title
Journal ISSN
Volume Title
Publisher
The Endocrine Society
Abstract
Acute systemic stress disrupts reproductive function by inhibiting pulsatile gonadotropin secretion.
The underlying mechanism involves stress-induced suppression of the GnRH pulse generator, the
functional unit of which is considered to be the hypothalamic arcuate nucleus kisspeptin/neurokinin
B/dynorphinAneurons. Agonists of the neurokininB(NKB) receptor (NK3R) have beenshown
to suppress the GnRH pulse generator, in a dynorphin A (Dyn)-dependent fashion, under hypoestrogenic
conditions, and Dyn has been well documented to mediate several stress-related central
regulatory functions. We hypothesized that the NKB/Dyn signaling cascade is required for stressinduced
suppression of the GnRH pulse generator. To investigate this ovariectomized rats, iv
administered with Escherichia coli lipopolysaccharide (LPS) following intracerebroventricular pretreatment
with NK3R or -opioid receptor (Dyn receptor) antagonists, were subjected to frequent
blood sampling for hormone analysis. Antagonism of NK3R, but not -opioid receptor, blocked the
suppressive effect of LPS challengeonLHpulse frequency. Neither antagonist affected LPS-induced
corticosterone secretion. Hypothalamic arcuate nucleus NKB neurons project to the paraventricular
nucleus, the major hypothalamic source of the stress-related neuropeptides CRH and arginine
vasopressin (AVP), which have been implicated in the stress-induced suppression of the hypothalamic-
pituitary-gonadal axis. A separate group of ovariectomized rats was, therefore, used to
address the potential involvement of central CRH and/or AVP signaling in the suppression of LH
pulsatility induced by intracerebroventricular administration of a selective NK3R agonist, senktide.
Neither AVP nor CRH receptor antagonists affected the senktide-induced suppression of the LH
pulse; however, antagonism of type 2 CRH receptors attenuated the accompanying elevation of
corticosterone levels. These data indicate that the suppression of the GnRH pulse generator by
acute systemic stress requires hypothalamic NKB/NK3R signaling and that any involvement of CRH
therewith is functionally upstream of NKB.
Description
Keywords
Stress, Reproduction, Acute systemic stress, GnRH pulse generator, Neurokinin B (NKB), NKB/NK3R signaling
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Citation
Grachev, P, Li, XF, Hu, MH, Li, SY, Millar, RP, Lightman, SL & O'Byrne, KT 2014, 'Neurokinin B signaling in the female rat : a novel link between stress and reproduction', Endocrinology, vol. 155, no. 7, pp. 2589-2601.