Please use this identifier to cite or link to this item: https://doi.org/10.1210/me.2013-1210
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dc.titleGonadotropin-releasing hormone-regulated prohibitin mediates apoptosis of the gonadotrope cells
dc.contributor.authorSavulescu, D.
dc.contributor.authorFeng, J.
dc.contributor.authorPing, Y.S.
dc.contributor.authorMai, O.
dc.contributor.authorBoehm, U.
dc.contributor.authorHe, B.
dc.contributor.authorO'Malley, B.W.
dc.contributor.authorMelamed, P.
dc.date.accessioned2014-10-27T08:29:41Z
dc.date.available2014-10-27T08:29:41Z
dc.date.issued2013
dc.identifier.citationSavulescu, D., Feng, J., Ping, Y.S., Mai, O., Boehm, U., He, B., O'Malley, B.W., Melamed, P. (2013). Gonadotropin-releasing hormone-regulated prohibitin mediates apoptosis of the gonadotrope cells. Molecular Endocrinology 27 (11) : 1856-1870. ScholarBank@NUS Repository. https://doi.org/10.1210/me.2013-1210
dc.identifier.issn08888809
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/100786
dc.description.abstractGnRH regulates circulating levels of the gonadotropins but has also been implicated in establishing the gonadotrope cell population. Consistent with this, GnRH induces proliferation of partially differentiated gonadotropes, while reducing the numbers of fully differentiated cells. We have previously reported that the proapoptotic protein, prohibitin (PHB) is expressed more abundantly in gonadotrope-derived LβT2 cells than in partially differentiated βT3-1 gonadotrope precursor cells, suggesting a possible role for PHB in GnRH-induced apoptosis. We show here that PHB is required for GnRH-induced apoptosis in mature gonadotropes. PHB expression and activity are regulated by GnRH: its transcription is via c-Jun NH2-terminal kinase, whereas its nuclear export follows activation of ERK. Moreover, PHB levels are down-regulated by microRNA27, which is expressed at lower levels in mature gonadotropes, possibly explaining the switch to an apoptotic response with development. PHB is required for mitochondrial import of the proapoptotic BAX, whose expression is also induced by GnRH-activated c-Jun NH2-terminal kinase, as is expression of the BH3-only protein, HRK, and this too plays a role in GnRH-induced apoptosis. Finally, we show that gonadotrope-specific PHB-knockout mice display reproductive abnormalities, including a larger gonadotrope population, increased LH levels, reduced fertility, and altered gonad development. We thus demonstrate a role for PHB in GnRH-induced cell death in mature gonadotropes, which is crucial for the normal development and function of the reproductive axis. © 2013 by The Endocrine Society.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1210/me.2013-1210
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1210/me.2013-1210
dc.description.sourcetitleMolecular Endocrinology
dc.description.volume27
dc.description.issue11
dc.description.page1856-1870
dc.description.codenMOENE
dc.identifier.isiut000326168300007
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