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Neurokinin B signaling in the female rat: a novel link between stress and reproduction
- Source :
- Endocrinology
- Publication Year :
- 2014
-
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/dynorphin A neurons. Agonists of the neurokinin B (NKB) receptor (NK3R) have been shown 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 stress-induced suppression of the GnRH pulse generator. To investigate this ovariectomized rats, iv administered with Escherichia coli lipopolysaccharide (LPS) following intracerebroventricular pretreatment with NK3R or κ-opioid receptor (Dyn receptor) antagonists, were subjected to frequent blood sampling for hormone analysis. Antagonism of NK3R, but not κ-opioid receptor, blocked the suppressive effect of LPS challenge on LH pulse 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.
- Subjects :
- Lipopolysaccharides
Receptors, Vasopressin
Vasopressin
Corticotropin-Releasing Hormone
Neurokinin B
Gonadotropin-releasing hormone
Substance P
Gonadotropin-Releasing Hormone
Rats, Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Kisspeptin
Receptor
Neurons
0303 health sciences
Reproduction
Dynorphin A
Receptors, Neurokinin-3
Gonadotropin secretion
Quinolines
Female
Antidiuretic Hormone Receptor Antagonists
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
medicine.medical_specialty
endocrine system
Ovariectomy
Neuropeptide
Biology
Receptors, Corticotropin-Releasing Hormone
03 medical and health sciences
Stress, Physiological
Internal medicine
medicine
Animals
Pyrroles
Injections, Intraventricular
030304 developmental biology
Arcuate Nucleus of Hypothalamus
Luteinizing Hormone
Peptide Fragments
Rats
Pyrimidines
chemistry
nervous system
Corticosterone
030217 neurology & neurosurgery
Subjects
Details
- Volume :
- 155
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....fd499dcf93d13070c0eafdd8ea76fdc5