Document Detail

Activation of soluble guanylyl cyclase inhibits estradiol production and cyclic AMP accumulation from cultured rat granulosa cells.
MedLine Citation:
PMID:  15474089     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To demonstrate the expression of soluble guanylyl cyclase (sGC) alpha and beta subunits in rat granulosa cells and determine the effects sGC activation on levels of cyclic GMP (cGMP), E2, and cAMP. DESIGN: Basic research study. SETTING: University research laboratory. ANIMAL(S): Estrogen-treated immature Sprague-Dawley female rats from which primary cell culture of granulosa cells was obtained. INTERVENTION(S): Functionally immature rat granulosa cells were incubated for 48 hours with media alone, FSH, or FSH plus YC-1, a specific activator of sGC. MAIN OUTCOME MEASURE(S): Expression of sGC alpha and beta subunits was determined by immunoblot analysis. Media concentrations of E2, cAMP, and cGMP were measured by radioimmunoassays. RESULT(S): Immunoblot analysis of granulosa cells revealed the expression of sGC alpha and beta subunits. While cGMP accumulation was low in cells incubated with media alone or with FSH, cotreatment with FSH plus YC-1 increased cGMP levels approximately five-fold. Incubation of cells with FSH stimulated E2 production in a dose-dependent manner. However, cotreatment of cells with FSH plus YC-1 significantly decreased E2 concentrations at all doses of FSH tested. Similarly, while FSH increased cAMP accumulation from granulosa cells, cotreatment with YC-1 markedly inhibited FSH-stimulated cAMP levels. CONCLUSION(S): These findings demonstrate the expression of sGC subunits in rat granulosa cells and indicate that activation of sGC increases cGMP levels, which are associated with inhibition of FSH-stimulated E2 production and cAMP accumulation.
Michael A Tafoya; Jean You-Hsin Chen; Robert L Stewart; Philip S Lapolt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Fertility and sterility     Volume:  82 Suppl 3     ISSN:  0015-0282     ISO Abbreviation:  Fertil. Steril.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-11     Completed Date:  2004-11-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372772     Medline TA:  Fertil Steril     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1154-9     Citation Subset:  IM    
Department of Biological Sciences, California State University, Los Angeles, California 90032, USA.
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MeSH Terms
Cells, Cultured
Cyclic AMP / antagonists & inhibitors*,  metabolism
Cyclic GMP / metabolism
Drug Synergism
Enzyme Activation / physiology
Enzyme Activators / pharmacology
Estradiol / biosynthesis*
Follicle Stimulating Hormone / pharmacology
Granulosa Cells / enzymology,  metabolism*
Guanylate Cyclase / chemistry,  metabolism*
Hormones / pharmacology
Indazoles / pharmacology
Isoenzymes / chemistry,  metabolism
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
0/Enzyme Activators; 0/Hormones; 0/Indazoles; 0/Isoenzymes; 154453-18-6/3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; 50-28-2/Estradiol; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; 9002-68-0/Follicle Stimulating Hormone; EC Cyclase

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