Document Detail

Progestin signaling through mPRα in Atlantic croaker granulosa/theca cell cocultures and its involvement in progestin inhibition of apoptosis.
MedLine Citation:
PMID:  20962051     Owner:  NLM     Status:  MEDLINE    
Although there is substantial evidence that membrane progestin receptors (mPRs) perform a critical physiological role in meiotic maturation of fish oocytes, it is unknown whether they are also intermediaries in progestin signaling in the surrounding follicular cells. Here, we show that mPRα protein is located on the plasma membranes of both granulosa and theca cells (G/T cells) isolated from Atlantic croaker ovaries and is associated with the presence of a single high affinity, limited capacity, pertussis toxin-sensitive, specific progestin [17,20β,21-trihydroxy-4-pregnen-3-one (20β-S)] membrane binding site with the characteristics of mPRα. Treatment of G/T cells with 20β-S caused rapid G protein activation and a transient, pertussis toxin-sensitive, decrease in cAMP levels, whereas the selective nuclear progesterone receptor agonist, R5020, did not cause G protein activation, consistent with previous reports on mPRα signaling. 20β-S treatment decreased serum starvation-induced cell death in both G/T cells and in seatrout mPRα-transfected MDA-MB-231 cells, whereas R5020 was ineffective. Moreover, a selective mPRα agonist, 10-ethenyl-19-norprogesterone, mimicked the protective action of 20β-S against cell death, which was lost upon knockdown of mPRα protein but not after progesterone receptor knockdown, further demonstrating an involvement of mPRα. Signaling molecules involved in inhibition of apoptosis, Erk and serine-threonine kinase, were activated in G/T cells by 20β-S, which suggests a potential mechanism for mPRα inhibition of apoptosis. This is the first study to demonstrate endogenous mPR signaling in the ovarian follicle and to suggest a novel physiological role for mPRα in mediating the antiapoptotic actions of progestins in ovarian follicle cells.
Gwen E Dressing; Yefei Pang; Jing Dong; Peter Thomas
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-20
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-04     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5916-26     Citation Subset:  AIM; IM    
University of Texas at Austin Marine Science Institute, Port Aransas, Texas 78373, USA.
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MeSH Terms
Cell Death
Cells, Cultured
Coculture Techniques
Cortodoxone / analogs & derivatives
Extracellular Signal-Regulated MAP Kinases / genetics,  metabolism
Granulosa Cells / cytology,  physiology*
Perciformes / physiology*
Proto-Oncogene Proteins c-akt / genetics,  metabolism
RNA, Small Interfering
Receptors, Progesterone / genetics,  metabolism*
Theca Cells / cytology,  physiology*
Grant Support
ESO 12961//PHS HHS
Reg. No./Substance:
0/Progestins; 0/RNA, Small Interfering; 0/Receptors, Progesterone; 152-58-9/Cortodoxone; 5786-59-4/17,20,21-trihydroxy-4-pregnen-3-one; EC Proteins c-akt; EC Signal-Regulated MAP Kinases

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