Circadian and kisspeptin regulation of the preovulatory surge

Piet, Richard

doi:10.1016/j.peptides.2023.170981

Cited by 10 publications

(6 citation statements)

References 240 publications

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“…Yet, VIP- or VPAC2- null mice remain fertile ( Harmar et al, 2002 ; Colwell et al, 2003 ) despite asynchronous SCNs ( Aton et al, 2005 ). The signal triggering ovulation at the appropriate time of the day is evident in species with short estrous cycle like rodents ( Barofsky and Harney, 1983 ; McElhinny et al, 1999 ; Piet, 2023 ). However, studies show that ovulation occurs at the end of the night or early morning in a majority of women, phase-locked with the circadian cortisol peak ( Cahill et al, 1998 ; Kerdelhue et al, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide excites GnRH neurons via KCa3.1, a potential player in the slow afterhyperpolarization current

Constantin,

Quignon,

Pizano

et al. 2024

Front. Cell. Neurosci.

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Vasoactive intestinal peptide (VIP) is an important component of the suprachiasmatic nucleus (SCN) which relays circadian information to neuronal populations, including GnRH neurons. Human and animal studies have shown an impact of disrupted daily rhythms (chronic shift work, temporal food restriction, clock gene disruption) on both male and female reproduction and fertility. To date, how VIP modulates GnRH neurons remains unknown. Calcium imaging and electrophysiology on primary GnRH neurons in explants and adult mouse brain slice, respectively, were used to address this question. We found VIP excites GnRH neurons via the VIP receptor, VPAC2. The downstream signaling pathway uses both Gs protein/adenylyl cyclase/protein kinase A (PKA) and phospholipase C/phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. Furthermore, we identified a UCL2077-sensitive target, likely contributing to the slow afterhyperpolarization current (IAHP), as the PKA and PIP2 depletion target, and the KCa3.1 channel as a specific target. Thus, VIP/VPAC2 provides an example of Gs protein-coupled receptor-triggered excitation in GnRH neurons, modulating GnRH neurons likely via the slow IAHP. The possible identification of KCa3.1 in the GnRH neuron slow IAHP may provide a new therapeutical target for fertility treatments.

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Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide excites GnRH neurons via KCa3.1, a potential player in the slow afterhyperpolarization current

Constantin,

Quignon,

Pizano

et al. 2024

Front. Cell. Neurosci.

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“…5-HT may mediate the permissive effect of the metabolic hormone leptin on the hypothalamic-pituitary-gonadal axis ( 79 ) and, indeed, the DR is involved in many aspects of energy balance ( 80 ). Additionally, 5-HT signaling may be involved in regulating circadian rhythms and responses to stressors ( 81 – 83 ), which also affect LH secretion and the surge ( 20 , 21 ). Further studies will be required to determine the precise contribution of changes in 5-HT neurotransmission in regulating the surge and whether this involves RP3V KISS1 neurons.…”

Section: Discussionmentioning

confidence: 99%

Serotonin stimulates female preoptic area kisspeptin neurons via activation of type 2 serotonin receptors in mice

Buo,

Bearss,

Novak

et al. 2023

Front. Endocrinol.

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BackgroundThe neuroendocrine control of ovulation is orchestrated by neuronal circuits that ultimately drive the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus to trigger the preovulatory surge in luteinizing hormone (LH) secretion. While estrogen feedback signals are determinant in triggering activation of GnRH neurons, through stimulation of afferent kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3VKISS1 neurons), many neuropeptidergic and classical neurotransmitter systems have been shown to regulate the LH surge. Among these, several lines of evidence indicate that the monoamine neurotransmitter serotonin (5-HT) has an excitatory, permissive, influence over the generation of the surge, via activation of type 2 5-HT (5-HT2) receptors. The mechanisms through which this occurs, however, are not well understood. We hypothesized that 5-HT exerts its influence on the surge by stimulating RP3VKISS1 neurons in a 5-HT2 receptor-dependent manner.MethodsWe tested this using kisspeptin neuron-specific calcium imaging and electrophysiology in brain slices obtained from male and female mice.ResultsWe show that exogenous 5-HT reversibly increases the activity of the majority of RP3VKISS1 neurons. This effect is more prominent in females than in males, is likely mediated directly at RP3VKISS1 neurons and requires activation of 5-HT2 receptors. The functional impact of 5-HT on RP3VKISS1 neurons, however, does not significantly vary during the estrous cycle.ConclusionTaken together, these data suggest that 5-HT2 receptor-mediated stimulation of RP3VKISS1 neuron activity might be involved in mediating the influence of 5-HT on the preovulatory LH surge.

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“…Multiple hypothalamic subregions coordinate the release of reproductive neuropeptides and hormones ( Plant, 2015 ), including kisspeptin within the arcuate (ARC) and anteroventral paraventricular (AVPV) nuclei, gonadotropin releasing hormone (GnRH) within the preoptic area (POA) and anterior hypothalamus, and RFamide-related peptide 3 (the mammalian ortholog of avian gonadotropin-inhibitory hormone) within the dorsomedial nucleus of the hypothalamus ( Ubuka et al, 2018 ; Angelopoulou et al, 2019 ). These populations integrate with the central clock in the suprachiasmatic nucleus (SCN) and extrahypothalamic regions to generate an exquisitely coordinated circadian-, ovulatory phase-, pulse-, and environmentally-modulated GnRH signal (reviewed in ( Moeller et al, 2022 ; Piet, 2023 )). GnRH is released to the portal vasculature of the anterior pituitary where it triggers the release of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH).…”

Section: Introductionmentioning

confidence: 99%

“…This change is coincident with rising levels of estradiol that peak prior to ovulation, and low concentrations of progesterone. In spontaneously-ovulating rodents, sufficiently elevated estradiol integrates with SCN vasopressin (AVP)-ergic circadian signaling at kisspeptin neurons of the AVPV to stimulate the LH surge that initiates ovulation ( Moeller et al, 2022 ; Moralia et al, 2022 ; Tonsfeldt et al, 2022 ; Piet, 2023 ). In addition, SCN vasoactive-intestinal polypeptide (VIP)-ergic projections to the POA also contribute to the LH surge via direct communication to GnRH cells ( Moeller et al, 2022 ; Moralia et al, 2022 ; Tonsfeldt et al, 2022 ; Piet, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…In spontaneously-ovulating rodents, sufficiently elevated estradiol integrates with SCN vasopressin (AVP)-ergic circadian signaling at kisspeptin neurons of the AVPV to stimulate the LH surge that initiates ovulation ( Moeller et al, 2022 ; Moralia et al, 2022 ; Tonsfeldt et al, 2022 ; Piet, 2023 ). In addition, SCN vasoactive-intestinal polypeptide (VIP)-ergic projections to the POA also contribute to the LH surge via direct communication to GnRH cells ( Moeller et al, 2022 ; Moralia et al, 2022 ; Tonsfeldt et al, 2022 ; Piet, 2023 ). Although numerous lines of evidence point to the negative impact of circadian disruption on ovulation in women, the SCN does not appear to be necessary for the LH surge in women and higher primates (reviewed in ( Moeller et al, 2022 )).…”

Section: Introductionmentioning

confidence: 99%

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Neural substrates underlying rhythmic coupling of female reproductive and thermoregulatory circuits

Grant,

Kriegsfeld

2023

Front. Physiol.

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Coordinated fluctuations in female reproductive physiology and thermoregulatory output have been reported for over a century. These changes occur rhythmically at the hourly (ultradian), daily (circadian), and multi-day (ovulatory) timescales, are critical for reproductive function, and have led to the use of temperature patterns as a proxy for female reproductive state. The mechanisms underlying coupling between reproductive and thermoregulatory systems are not fully established, hindering the expansion of inferences that body temperature can provide about female reproductive status. At present, numerous digital tools rely on temperature to infer the timing of ovulation and additional applications (e.g., monitoring ovulatory irregularities and progression of puberty, pregnancy, and menopause are developed based on the assumption that reproductive-thermoregulatory coupling occurs across timescales and life stages. However, without clear understanding of the mechanisms and degree of coupling among the neural substrates regulating temperature and the reproductive axis, whether such approaches will bear fruit in particular domains is uncertain. In this overview, we present evidence supporting broad coupling among the central circuits governing reproduction, thermoregulation, and broader systemic physiology, focusing on timing at ultradian frequencies. Future work characterizing the dynamics of reproductive-thermoregulatory coupling across the lifespan, and of conditions that may decouple these circuits (e.g., circadian disruption, metabolic disease) and compromise female reproductive health, will aid in the development of strategies for early detection of reproductive irregularities and monitoring the efficacy of fertility treatments.

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Circadian and kisspeptin regulation of the preovulatory surge

Cited by 10 publications

References 240 publications

Vasoactive intestinal peptide excites GnRH neurons via KCa3.1, a potential player in the slow afterhyperpolarization current

Vasoactive intestinal peptide excites GnRH neurons via KCa3.1, a potential player in the slow afterhyperpolarization current

Serotonin stimulates female preoptic area kisspeptin neurons via activation of type 2 serotonin receptors in mice

Neural substrates underlying rhythmic coupling of female reproductive and thermoregulatory circuits

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