Vasopressinergic Activity of the Suprachiasmatic Nucleus and mRNA Expression of Clock Genes in the Hypothalamus-Pituitary-Gonadal Axis in Female Aging DOI Creative Commons
Angela Cristina de Nicola,

Larissa Brazoloto Ferreira,

Milene Mantovani Mata

et al.

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 24, 2021

The important involvement of the suprachiasmatic nucleus (SCN) and activity vasopressinergic neurons in maintaining rhythmicity female reproductive system depends on mRNA transcription-translation feedback loops. Therefore, circadian clock function, like most physiological processes, is involved events that determine aging. This study describes change expression genes, Per2 , Bmal1 Rev-erbα hypothalamus-pituitary-gonadal axis (HPG) rats with regular cycle (RC) irregular (IC), SCN kisspeptin arcuate (ARC) these animals. Results for gonadotropins cFos/AVP-ir IC were higher, but kisspeptin-ir was minor. Change temporal synchrony HPG axis, during period prior to cessation ovulatory cycles, identified. analysis adult rodents shows regularity estrous guaranteed by alternation amount Bmal 1 between light dark phases, which ceases occur contributes determining senescence. These results showed desynchronization central peripheral clocks irregularity events. We suggest loops genes modulate spontaneous transition from acyclicity rodents.

Language: Английский

The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction DOI Creative Commons
Qinying Xie,

Yafei Kang,

Chenlu Zhang

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 28, 2022

The discovery of kisspeptin as a critical central regulatory factor GnRH release has given people novel understanding the neuroendocrine regulation in human reproduction. Kisspeptin activates signaling pathway by binding to its receptor (KISS1R) promote secretion, thereby regulating hypothalamic-pituitary-gonadal axis (HPG) axis. Recent studies have shown that neurons located arcuate nucleus (ARC) co-express neurokinin B (NKB) and dynorphin (Dyn). Such are called KNDy neurons. participate positive negative feedback estrogen secretion. In addition, is key initiation puberty, also regulates processes female follicle development, oocyte maturation, ovulation through HPG male reproduction, plays an important role, getting involved Leydig cells, spermatogenesis, sperm functions reproductive behaviors. Mutations KISS1 gene or disorders kisspeptin/KISS1R system may lead clinical symptoms such idiopathic hypogonadotropic hypogonadism (iHH), precocious puberty (CPP) infertility. Understanding influence on related mechanisms will help future application disease diagnosis treatment. this review, we critically appraise role axis, including pathways, mechanisms, control

Language: Английский

Citations

111
MC3R links nutritional state to childhood growth and the timing of puberty DOI
Brian Lam, Alice Williamson, Sarah Finer

et al.

Nature, Journal Year: 2021, Volume and Issue: 599(7885), P. 436 - 441

Published: Nov. 3, 2021

Language: Английский

Citations

101
The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty DOI Open Access
Vinicius Nahime Brito, Ana Pinheiro Machado Canton, Carlos Eduardo Seraphim

et al.

Endocrine Reviews, Journal Year: 2022, Volume and Issue: 44(2), P. 193 - 221

Published: Aug. 5, 2022

The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital acquired causes that can be associated with structural or functional brain alterations. All CPP culminate in the premature pulsatile secretion hypothalamic GnRH and, consequently, reactivation hypothalamic-pituitary-gonadal axis. activation excitatory factors suppression inhibitory during childhood represent 2 major mechanisms CPP, revealing a delicate balance these opposing neuronal pathways. Hypothalamic hamartoma (HH) most well-known cause nervous system abnormalities. Several by which have been proposed, an anatomical connection to anterior hypothalamus, autonomous neuroendocrine activity neurons, trophic secreted HH, mechanical pressure applied hypothalamus. importance genetic and/or epigenetic underlying has grown significantly last decade, as demonstrated evidence abnormalities lesions (eg, hamartomas, gliomas), syndromic disorders (Temple, Prader-Willi, Silver-Russell, Rett syndromes), isolated from monogenic defects (MKRN3 DLK1 loss-of-function mutations). Genetic discoveries involving had influence on diagnosis familial counseling providing bases for potential prevention sexual development new treatment targets future. Global preventive actions inducing healthy lifestyle habits less exposure endocrine-disrupting chemicals lifespan are desirable because they potentially CPP.

Language: Английский

Citations

54
Neuroendocrine interactions of the stress and reproductive axes DOI Creative Commons
Chayarndorn Phumsatitpong,

Elizabeth R. Wagenmaker,

Suzanne M. Moenter

et al.

Frontiers in Neuroendocrinology, Journal Year: 2021, Volume and Issue: 63, P. 100928 - 100928

Published: June 24, 2021

Language: Английский

Citations

43
Modulation of pulsatile GnRH dynamics across the ovarian cycle via changes in the network excitability and basal activity of the arcuate kisspeptin network DOI Creative Commons
Margaritis Voliotis, Xiao Feng Li,

Ross Alexander De Burgh

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Nov. 17, 2021

Pulsatile GnRH release is essential for normal reproductive function. Kisspeptin secreting neurons found in the arcuate nucleus, known as KNDy co-expressing neurokinin B, and dynorphin, drive pulsatile release. Furthermore, gonadal steroids regulate dynamics across ovarian cycle by altering neurons' signalling properties. However, precise mechanism of regulation remains mostly unknown. To better understand these mechanisms, we start perturbing system at different stages estrous using optogenetics. We find that optogenetic stimulation stimulates GnRH/LH secretion mice but inhibits it diestrous mice. These vivo results combination with mathematical modelling suggest transition between estrus diestrus underpinned well-orchestrated changes neuropeptide excitability population controlled via glutamate signalling. Guided model predictions, show blocking animals LH pulses, optic mitigates this inhibition. In mice, disruption pulses generated sustained low-frequency population, supporting idea level network critical pulse generation. Our reconcile previous puzzling findings regarding estradiol-dependent effect several neuromodulators have on generator dynamics. Therefore, anticipate our to be a cornerstone more quantitative understanding pathways which Finally, could inform useful repurposing drugs targeting therapy.

Language: Английский

Citations

34
Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression DOI Creative Commons

Hollis Wright,

Carlos F. Aylwin, Carlos A. Toro

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Jan. 21, 2021

Abstract Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1 , a puberty-activating gene, key target of this silencing mechanism. Using gain-of-function approach and systems biology strategy we now show that EED, an essential PcG component, acts in the arcuate nucleus hypothalamus alter functional organization gene network involved stimulatory control puberty. A central node Kdm6b which encodes enzyme erases PcG-dependent histone modification H3K27me3. first neighbor network; genes encoding glutamatergic receptors potassium channels are second neighbors. By repressing expression, EED increases H3K27me3 abundance at these promoters, reducing expression throughout controlling activation. These results indicate repression basic mechanism used by modulate biological output networks.

Language: Английский

Citations

33
Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System DOI
Vikash Prashar,

Tania Arora,

Randeep Singh

et al.

Reproductive Sciences, Journal Year: 2022, Volume and Issue: 30(3), P. 802 - 822

Published: July 7, 2022

Language: Английский

Citations

21
Dissecting the KNDy hypothesis: KNDy neuron-derived kisspeptins are dispensable for puberty but essential for preserved female fertility and gonadotropin pulsatility DOI Creative Commons
Inmaculada Velasco, Delphine Franssen, Silvia Daza‐Dueñas

et al.

Metabolism, Journal Year: 2023, Volume and Issue: 144, P. 155556 - 155556

Published: April 28, 2023

Language: Английский

Citations

12
Changes of Signaling Pathways in Hypothalamic Neurons with Aging DOI Creative Commons
П. М. Маслюков

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(10), P. 8289 - 8308

Published: Oct. 12, 2023

The hypothalamus is an important regulator of autonomic and endocrine functions also involved in aging regulation. process the accompanied by disturbed intracellular signaling including insulin/insulin-like growth factor-1 (IGF-1)/growth hormone (GH), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/the mammalian target rapamycin (mTOR), mitogen activated protein (MAPK), janus (JAK)/signal transducer activator transcription (STAT), AMP-activated (AMPK), nuclear factor kappa-light-chain-enhancer cells (NF-ĸB), nitric oxide (NO). In current review, I have summarized understanding changes above-mentioned pathways with a focus on hypothalamic alterations.

Language: Английский

Citations

10
Role of membrane estrogen receptor alpha on the negative feedback of estrogens on luteinizing hormone secretion DOI Open Access

Mélanie Faure,

Rebeca Corona,

Laura Vandries

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contributions of its nuclear and membrane signaling are unclear.The present study investigated role ERα (mERα) using two complementary approaches: a mouse model lacking mERα (C451A‐ERα mice) estetrol (E 4 ), natural estrogen described to prevent activation in different cell types. While ovariectomy (OVX) induced comparable luteinizing hormone (LH) increase both wild‐type C451A‐ERα females, females failed respond chronic estradiol 2 ) (1 μg) exposure, indicating dysregulated negative feedback. This lack LH regulation was mirrored by an absence change number neurons immunoreactive (ir) kisspeptin (Kp) rostral periventricular area third ventricle (RP3V) arcuate nucleus (ARC), progesterone (PR)‐ir nuclei preoptic hypothalamus, neurokinin 3 (NK R) ARC. Interestingly, increasing dose E 5 μg restored normal feedback numbers Kp‐ir PR‐ir nuclei, not surface covered fibers NK R‐ir By contrast, mimicked on circulating OVX WT following acute treatment potentiated rather than blocked effects when administered along with it. also stimulatory several hypothalamic regions percentage material ARC, as well inhibitory action Therefore, mutation interferes control through distinct mechanisms differing their dose‐dependency . all associated neural circuits, that acts weak agonist this context. Together, these results suggest modifies sensitivity , impacting regulation.

Language: Английский

Citations

0