PMID- 26465008 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151014 LR - 20181113 IS - 2373-2822 (Print) IS - 2373-2822 (Electronic) IS - 2373-2822 (Linking) VI - 2 IP - 4 DP - 2015 Jul-Aug TI - Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus. LID - 10.1523/ENEURO.0012-15.2015 [doi] LID - ENEURO.0012-15.2015 AB - Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs). PRs are expressed as two isoforms, PR-A and PR-B, that have distinct functions in physiology and behavior. Because these PR isoforms cannot be distinguished using cellular resolution techniques, the present study used isoform-specific null mutant mice that lack PR-A or PR-B for the first time to investigate whether 17beta-estradiol benzoate (EB) regulates the differential expression of the PR isoforms in the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus, and medial preoptic area, brain regions that are rich in EB-induced PRs. Interestingly, EB induced more PR-A than PR-B in all three brain regions, suggesting that PR-A is the predominant isoform in these regions. Given that steroid receptor coactivator (SRC)-1 and SRC-2 are important in estrogen receptor (ER)-dependent transcription in brain, including PR induction, we tested whether the expression of these coactivators was correlated with PR isoform expression. The majority of EB-induced PR cells expressed both SRC-1 and SRC-2 in the three brain regions of all genotypes. Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner. In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology. FAU - Acharya, Kalpana D AU - Acharya KD AD - Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481. FAU - Finkelstein, Sarah D AU - Finkelstein SD AD - Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481. FAU - Bless, Elizabeth P AU - Bless EP AD - Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481. FAU - Nettles, Sabin A AU - Nettles SA AD - Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481. FAU - Mulac-Jericevic, Biserka AU - Mulac-Jericevic B AD - Department of Molecular and Cellular Biology, Baylor College of Medicine , Houston, Texas 77030. FAU - Conneely, Orla M AU - Conneely OM AD - Department of Molecular and Cellular Biology, Baylor College of Medicine , Houston, Texas 77030. FAU - Mani, Shaila K AU - Mani SK AD - Department of Molecular and Cellular Biology, Baylor College of Medicine , Houston, Texas 77030. FAU - Tetel, Marc J AU - Tetel MJ AD - Neuroscience Program, Wellesley College , Wellesley, Massachusetts 02481. LA - eng GR - R01 DK061935/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20150813 PL - United States TA - eNeuro JT - eNeuro JID - 101647362 PMC - PMC4596027 OTO - NOTNLM OT - SRC-1 OT - estrogens OT - female reproduction OT - progesterone OT - steroid receptor coactivator OT - ventromedial hypothalamus COIS- The authors declare no conflicting financial interests. EDAT- 2015/10/16 06:00 MHDA- 2015/10/16 06:01 PMCR- 2015/08/13 CRDT- 2015/10/15 06:00 PHST- 2015/01/30 00:00 [received] PHST- 2015/07/24 00:00 [revised] PHST- 2015/07/25 00:00 [accepted] PHST- 2015/10/15 06:00 [entrez] PHST- 2015/10/16 06:00 [pubmed] PHST- 2015/10/16 06:01 [medline] PHST- 2015/08/13 00:00 [pmc-release] AID - eN-NWR-0012-15 [pii] AID - 10.1523/ENEURO.0012-15.2015 [doi] PST - epublish SO - eNeuro. 2015 Aug 13;2(4):ENEURO.0012-15.2015. doi: 10.1523/ENEURO.0012-15.2015. eCollection 2015 Jul-Aug.