PMID- 19324971 OWN - NLM STAT- MEDLINE DCOM- 20091012 LR - 20211020 IS - 1944-9917 (Electronic) IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 23 IP - 7 DP - 2009 Jul TI - Estrogen receptor beta is required for optimal cAMP production in mouse granulosa cells. PG - 955-65 LID - 10.1210/me.2008-0213 [doi] AB - 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. FAU - Deroo, Bonnie J AU - Deroo BJ AD - Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. FAU - Rodriguez, Karina F AU - Rodriguez KF FAU - Couse, John F AU - Couse JF FAU - Hamilton, Katherine J AU - Hamilton KJ FAU - Collins, Jennifer B AU - Collins JB FAU - Grissom, Sherry F AU - Grissom SF FAU - Korach, Kenneth S AU - Korach KS LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20090326 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (Estrogen Receptor beta) RN - 0 (Receptors, LH) RN - 1F7A44V6OU (Colforsin) RN - 9002-67-9 (Luteinizing Hormone) RN - E0399OZS9N (Cyclic AMP) SB - IM MH - Animals MH - Cells, Cultured MH - Colforsin/pharmacology MH - Cyclic AMP/*metabolism MH - Down-Regulation/drug effects/genetics MH - Estrogen Receptor beta/genetics/metabolism/*physiology MH - Female MH - Fertility/genetics MH - Granulosa Cells/drug effects/*metabolism MH - Luteinizing Hormone/pharmacology MH - Mice MH - Mice, Knockout MH - Ovulation/genetics/metabolism MH - Receptors, LH/genetics/metabolism PMC - PMC2703605 EDAT- 2009/03/28 09:00 MHDA- 2009/10/13 06:00 PMCR- 2010/07/01 CRDT- 2009/03/28 09:00 PHST- 2009/03/28 09:00 [entrez] PHST- 2009/03/28 09:00 [pubmed] PHST- 2009/10/13 06:00 [medline] PHST- 2010/07/01 00:00 [pmc-release] AID - me.2008-0213 [pii] AID - 4454 [pii] AID - 10.1210/me.2008-0213 [doi] PST - ppublish SO - Mol Endocrinol. 2009 Jul;23(7):955-65. doi: 10.1210/me.2008-0213. Epub 2009 Mar 26.