+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Classical and membrane-initiated estrogen signaling in an in vitro model of anterior hypothalamic kisspeptin neurons

Classical and membrane-initiated estrogen signaling in an in vitro model of anterior hypothalamic kisspeptin neurons

Endocrinology 156(6): 2162-2173

The neuropeptide kisspeptin is essential for sexual maturation and reproductive function. In particular, kisspeptin-expressing neurons in the anterior rostral periventricular area of the third ventricle are generally recognized as mediators of estrogen positive feedback for the surge release of LH, which stimulates ovulation. Estradiol induces kisspeptin expression in the neurons of the rostral periventricular area of the third ventricle but suppresses kisspeptin expression in neurons of the arcuate nucleus that regulate estrogen-negative feedback. To focus on the intracellular signaling and response to estradiol underlying positive feedback, we used mHypoA51 cells, an immortalized line of kisspeptin neurons derived from adult female mouse hypothalamus. mHypoA51 neurons express estrogen receptor (ER)-α, classical progesterone receptor (PR), and kisspeptin, all key elements of estrogen-positive feedback. As with kisspeptin neurons in vivo, 17β-estradiol (E2) induced kisspeptin and PR in mHypoA51s. The ERα agonist, 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, produced similar increases in expression, indicating that these events were mediated by ERα. However, E2-induced PR up-regulation required an intracellular ER, whereas kisspeptin expression was stimulated through a membrane ER activated by E2 coupled to BSA. These data suggest that anterior hypothalamic kisspeptin neurons integrate both membrane-initiated and classical nuclear estrogen signaling to up-regulate kisspeptin and PR, which are essential for the LH surge.

(PDF emailed within 0-6 h: $19.90)

Accession: 057411785

Download citation: RISBibTeXText

PMID: 25730107

DOI: 10.1210/en.2014-1803

Related references

Membrane-initiated estrogen signaling in hypothalamic neurons. Molecular and Cellular Endocrinology 290(1-2): 14-23, 2008

Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice. Endocrinology 157(9): 3604-3620, 2017

Membrane-initiated estradiol signaling in immortalized hypothalamic N-38 neurons. Steroids 78(6): 607-613, 2014

β-arrestin regulates estradiol membrane-initiated signaling in hypothalamic neurons. Plos One 10(3): E0120530, 2016

Estrogen and Progesterone Integration in an in vitro Model of RP3V Kisspeptin Neurons. Neuroendocrinology 106(2): 101-115, 2017

Kisspeptin-GPR54 signaling in mouse NO-synthesizing neurons participates in the hypothalamic control of ovulation. Journal of Neuroscience 32(3): 932-945, 2012

Glutamatergic Transmission to Hypothalamic Kisspeptin Neurons Is Differentially Regulated by Estradiol through Estrogen Receptor α in Adult Female Mice. Journal of Neuroscience 38(5): 1061-1072, 2017

Estrogen permits vasopressin signaling in preoptic kisspeptin neurons in the female mouse. Journal of Neuroscience 35(17): 6881-6892, 2015

Rbpj-κ mediated Notch signaling plays a critical role in development of hypothalamic Kisspeptin neurons. Developmental Biology 406(2): 235-246, 2016

A variant of estrogen receptor-a, hER-a36: Transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling. Proceedings of the National Academy of Sciences of the United States of America 103(24): 63-8, 2006

Kisspeptin cell-specific PI3K signaling regulates hypothalamic kisspeptin expression and participates in the regulation of female fertility. American Journal of Physiology. Endocrinology and Metabolism 307(11): E969-E982, 2015

Synuclein gamma stimulates membrane-initiated estrogen signaling by chaperoning estrogen receptor (ER)-alpha36, a variant of ER-alpha. American Journal of Pathology 177(2): 964-973, 2011

Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proceedings of the National Academy of Sciences of the United States of America 107(52): 22693-8, 2011

Rapid signaling of estrogen in hypothalamic neurons involves a novel estrogen receptor that is G protein - coupled to activation of PKC. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 504 7, 2003

Kisspeptin directly regulates neuropeptide Y synthesis and secretion via the ERK1/2 and p38 mitogen-activated protein kinase signaling pathways in NPY-secreting hypothalamic neurons. Endocrinology 151(10): 5038-5047, 2010