Document Detail

Estrogen receptor beta is required for optimal cAMP production in mouse granulosa cells.
MedLine Citation:
PMID:  19324971     Owner:  NLM     Status:  MEDLINE    
Granulosa cells of preovulatory follicles differentiate in response to FSH, and this differentiation is augmented by estradiol. We have previously shown that FSH-mediated granulosa cell differentiation requires functional estrogen receptor-beta (ERbeta) by demonstrating that the granulosa cells of ERbeta(-/-) FSH-treated mice are unable to maximally induce expression of the LH receptor (an indicator of granulosa cell differentiation) compared with ERbeta(+/+) controls. As a result, FSH-primed ERbeta(-/-) granulosa cells exhibit a reduced response to a subsequent ovulatory dose of LH. In this study, we further characterized the attenuated response of ERbeta(-/-) granulosa cells to stimulation by LH and FSH using isolated mouse granulosa cells and primary granulosa cell cultures. We observed a 50% reduction in cAMP levels in cultured ERbeta(-/-) granulosa cells exposed to LH compared with ERbeta(+/+) controls. We also observed an attenuated genomic response in granulosa cells isolated from FSH-primed ERbeta(-/-) mice compared with ERbeta(+/+) controls. Our data indicate that this attenuated response may result from inadequate levels of cAMP, because cAMP levels in cultured ERbeta(-/-) granulosa cells exposed to forskolin were approximately 50% lower than in ERbeta(+/+) granulosa cells. Phosphorylation of cAMP regulatory element binding protein, an indicator of protein kinase A activity, was also reduced in FSH-treated ERbeta(-/-) granulosa cells compared with ERbeta(+/+) controls. These are the first data to indicate that ERbeta plays a role in the induction of the cAMP pathway in mouse granulosa cells and that disruption of proper ERbeta signaling associated with this pathway may cause negative effects on ovulation and fertility.
Bonnie J Deroo; Karina F Rodriguez; John F Couse; Katherine J Hamilton; Jennifer B Collins; Sherry F Grissom; Kenneth S Korach
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2009-03-26
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  23     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-10-12     Revised Date:  2013-03-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  955-65     Citation Subset:  IM    
Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
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MeSH Terms
Cells, Cultured
Cyclic AMP / metabolism*
Down-Regulation / drug effects,  genetics
Estrogen Receptor beta / genetics,  metabolism,  physiology*
Fertility / genetics
Forskolin / pharmacology
Granulosa Cells / drug effects,  metabolism*
Luteinizing Hormone / pharmacology
Mice, Knockout
Ovulation / genetics,  metabolism
Receptors, LH / genetics,  metabolism
Reg. No./Substance:
0/Estrogen Receptor beta; 0/Receptors, LH; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 9002-67-9/Luteinizing Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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