Circadian Control of the Female Reproductive Axis Through Gated Responsiveness of the RFRP-3 System to VIP Signaling

Russo, Kimberly A; La, Janet; Stephens, Shannon B. Z.; Poling, Matthew C.; Padgaonkar, Namita A.; Jennings, Kimberly J.; Piekarski, David J.; Kauffman, Alexander S.; Kriegsfeld, Lance J.

doi:10.1210/en.2014-1762

Cited by 63 publications

(74 citation statements)

References 65 publications

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“…17 and activities of the SCN, GnRH, and GnIH neurons are coordinated with ovulation (Gibson et al, 2008). Russo et al (2015) examined the specific neurochemical means by which the SCN controls GnIH activity and explored whether the GnIH system exhibits time-dependent responsiveness to SCN signaling to precisely time the LH surge. They found that GnIH cells in female hamsters receive close appositions from SCN-derived vasoactive intestinal polypeptide (VIP)-ergic terminal fibers.…”

Section: Regulation Of Estrous or Menstrual Cycle In Female Mammalsmentioning

confidence: 99%

“…Central VIP administration markedly suppresses GnIH cellular activity in the evening, but not the morning (Table 1). However, double-label in situ hybridization for GnIH and the VIP receptors, VPAC1and VPAC2, revealed that the majority of GnIH cells do not co-express either receptor in Syrian hamsters or mice, suggesting that SCN VIP-ergic signaling inhibits GnIH cells indirectly (Russo et al, 2015). Molnár et al (2011) investigated if GnIH neurons are involved in estrogen feedback signaling in mice.…”

Section: Regulation Of Estrous or Menstrual Cycle In Female Mammalsmentioning

confidence: 99%

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Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Ubuka

Son

Tsutsui

2016

General and Comparative Endocrinology

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Section: Regulation Of Estrous or Menstrual Cycle In Female Mammalsmentioning

confidence: 99%

Section: Regulation Of Estrous or Menstrual Cycle In Female Mammalsmentioning

confidence: 99%

Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Ubuka

Son

Tsutsui

2016

General and Comparative Endocrinology

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“…GnRH neuronal processes, named “dendrons,” by Herbison group [3], form an interwoven network that receives direct synaptic and neuropeptide input from upstream regulatory neurons, most notably kisspeptin [4, 5]. This GnRH network integrates other signals that impinge on reproduction, such as stress [6, 7], endocrine disruptors [8], circadian rhythms [9, 10], metabolism [11, 12], and acute inflammation during infection [13-15]. …”

Section: Introductionmentioning

confidence: 99%

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Lainez

Coss²

2019

Neuroendocrinology

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Background: The mechanisms whereby neuroinflammation negatively affects neuronal function in the hypothalamus are not clear. Our previous study determined that obesity-mediated chronic inflammation elicits sex-specific impairment in reproductive function via reduction in spine density in gonadotropin-releasing hormone (GnRH) neurons. Neuroinflammation and subsequent decrease in GnRH neuron spine density was specific for male mice, while protection in females was independent of ovarian estrogens. Methods: To examine if neuroinflammation-induced cytokines can directly regulate GnRH gene expression, herein we examined signaling pathways and mechanisms in males in vivo and in GnRH-expressing cell line, GT1–7. Results: GnRH neurons express cytokine receptors, and chronic or acute neuroinflammation represses GnRH gene expression in vivo. Leukemia inhibitory factor (LIF) in particular represses GnRH expression in GT1–7 cells, while other cytokines do not. STAT3 and MAPK pathways are activated following LIF treatment, but only MAPK pathway, specifically p38α, is sufficient to repress the GnRH gene. LIF induces cFOS that represses the GnRH gene via the -1,793 site in the enhancer region. In vivo, following high-fat diet, cFOS is induced in GnRH neurons and neurons juxtaposed to the leaky blood brain barrier of the organum vasculosum of the lamina terminalis, but not in the neurons further away. Conclusion: Our results indicate that the increase in LIF due to neuroinflammation induces cFOS and represses the GnRH gene. Therefore, in addition to synaptic changes in GnRH neurons, neuroinflammatory cytokines directly regulate gene expression and reproductive function, and the specificity for neuronal targets may stem from the proximity to the fenestrated capillaries.

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“…However, just prior to ovulation, peak E 2 concentrations act via positive‐feedback to initiate the LH surge that triggers ovulation . Previous findings by our group and others suggest that the temporary shift from negative‐ to positive‐feedback is coordinated by the SCN …”

Section: Introductionmentioning

confidence: 77%

Time‐of‐day‐dependent sensitivity of the reproductive axis to RFamide‐related peptide‐3 inhibition in female Syrian hamsters

Gotlieb

Baker

Moeller

et al. 2019

J Neuroendocrinology

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In spontaneously ovulating rodent species, the timing of the luteinising hormone (LH) surge is controlled by the master circadian pacemaker in the suprachiasmatic nucleus (SCN). The SCN initiates the LH surge via the coordinated control of two opposing neuropeptidergic systems that lie upstream of the gonadotrophin‐releasing hormone (GnRH) neuronal system: the stimulatory peptide, kisspeptin, and the inhibitory peptide, RFamide‐related peptide‐3 (RFRP‐3; the mammalian orthologue of avian gonadotrophin‐inhibitory hormone [GnIH]). We have previously shown that the GnRH system exhibits time‐dependent sensitivity to kisspeptin stimulation, further contributing to the precise timing of the LH surge. To examine whether this time‐dependent sensitivity of the GnRH system is unique to kisspeptin or a more common mechanism of regulatory control, we explored daily changes in the response of the GnRH system to RFRP‐3 inhibition. Female Syrian hamsters were ovariectomised to eliminate oestradiol (E2)‐negative‐feedback and RFRP‐3 or saline was centrally administered in the morning or late afternoon. LH concentrations and Lhβ mRNA expression did not differ between morning RFRP‐3‐and saline‐treated groups, although they were markedly suppressed by RFRP‐3 administration in the afternoon. However, RFRP‐3 inhibition of circulating LH at the time of the surge does not appear to act via the GnRH system because no differences in medial preoptic area Gnrh or RFRP‐3 receptor Gpr147 mRNA expression were observed. Rather, RFRP‐3 suppressed arcuate nucleus Kiss1 mRNA expression and potentially impacted pituitary gonadotrophs directly. Taken together, these findings reveal time‐dependent responsiveness of the reproductive axis to RFRP‐3 inhibition, possibly via variation in the sensitivity of arcuate nucleus kisspeptin neurones to this neuropeptide.

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Circadian Control of the Female Reproductive Axis Through Gated Responsiveness of the RFRP-3 System to VIP Signaling

Cited by 63 publications

References 65 publications

Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Time‐of‐day‐dependent sensitivity of the reproductive axis to RFamide‐related peptide‐3 inhibition in female Syrian hamsters

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