Membrane progestin receptor expression, signaling and function in reproductive somatic cells of female vertebrates

dc.contributor.advisorThomas, P. (Peter)en
dc.creatorDressing, Gwen Ellen, 1980-en
dc.date.accessioned2008-08-29T00:23:32Zen
dc.date.available2008-08-29T00:23:32Zen
dc.date.issued2008-05en
dc.descriptiontexten
dc.description.abstractThe goal of the current research was to examine the expression, signaling and function of the membrane progestin receptors (mPRs) in the ovarian follicular cells of the Atlantic croaker (Micropogonias undulatus) and in human breast cancer cells. Multiple studies have examined the role of mPRs in the germ cells of several vertebrate classes, yet few studies have examined the role of the mPRs in the somatic cells of reproductive tissues. Therefore this research examines the mechanism of mPR action and its function in somatic cells of female reproductive tissues. Results from studies on the expression, localization and signaling of the mPR[alpha] in co-cultures of granulosa and theca cells from the croaker suggest that the mPR[alpha] is localized to the plasma membrane of both cell types and that the mPR[alpha] is associated with and signals via pertussis toxin-sensitive inhibitory G proteins to decrease intracellular cAMP and activate ERK. In addition, exposure of follicular co-cultures to progestins that activate the mPR[alpha] results in a decrease in serum starvation-induced cell death which is not replicated by progestins which activate the nuclear progestin receptor (nPR), indicating mPR mediation. Similar studies in two immortalized human breast cancer cell lines, MDA-MB-468 and SKBR3, suggest that the mPR[alpha] is also present in the membranes of these cells and signals in human breast cancer cell lines via activation of a pertussis toxin-sensitive G protein to significantly decrease in intracellular cAMP and activate ERK. Progesterone exposure also decreased serum starvation-induced cell death in SKBR3 cells which are nPR positive and in MDA-MB-468 cells which are nPR negative. Synthetic progestins which activate the nPR but not the mPR were ineffective in inhibiting death in either cell type suggesting that the mPR is the mediator of this progestin action. mPR[alpha], mPR[beta] and mPR[gamma] expression analysis of paired normal and malignant breast tissue biopsies from thirteen women revealed that at least one mPR isoform was upregulated in the malignant tissue of 70% of the women. In addition the expression of mPR[gamma] was positively correlated with the expression of the nPR and CK19, a breast epithelial cell marker.en
dc.description.departmentMarine Scienceen
dc.format.mediumelectronicen
dc.identifierb70703620en
dc.identifier.oclc244252570en
dc.identifier.urihttp://hdl.handle.net/2152/3978en
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshProgesterone--Receptorsen
dc.subject.lcshSomatic cellsen
dc.subject.lcshCellular control mechanismsen
dc.subject.lcshApoptosisen
dc.subject.lcshCancer cellsen
dc.subject.lcshAtlantic croakeren
dc.subject.lcshBreast--Canceren
dc.titleMembrane progestin receptor expression, signaling and function in reproductive somatic cells of female vertebratesen
dc.type.genreThesisen
thesis.degree.departmentMarine Science Instituteen
thesis.degree.disciplineMarine Scienceen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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