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Estrogen response element-independent estrogen receptor (ER)-alpha signaling does not rescue sexual behavior but restores normal testosterone secretion in male ERalpha knockout mice



Estrogen response element-independent estrogen receptor (ER)-alpha signaling does not rescue sexual behavior but restores normal testosterone secretion in male ERalpha knockout mice



Endocrinology 148(11): 5288-5294



Estrogen receptor (ER)-alpha mediates estradiol (E-2) actions in the male gonads and brain and is critical for normal male reproductive function. In the classical pathway, ER alpha binds to estrogen response elements (EREs) to regulate gene transcription. ER alpha can also regulate gene transcription independently of EREs via protein-protein interactions with transcription factors and additionally signal via rapid, non-genomic pathways originating at the cell membrane. This study assessed the degree to which ERE-independent ER alpha signaling can rescue the disrupted masculine sexual behaviors and elevated serum testosterone ( T) levels that have been shown to result from ER alpha gene deletion. We utilized male ER alpha null mice that possess a ER knock-in mutation (E207A/G208A; AA), in which the mutant ER alpha is incapable of binding to DNA and can signal only through ERE-independent pathways (ER alpha(-/AA) mice). We found that sexual behavior, including mounting, is virtually absent in ER alpha(-/-) and ER alpha(-/AA) males, suggesting that ERE-independent signaling is insufficient to maintain any degree of normal sexual behavior in the absence of ERE binding. By contrast, ERE-independent signaling in the ER alpha(-/AA) mouse is sufficient to restore serum T levels to values observed in wild-type males. These data indicate that binding of ERs to EREs mediates most if not all of E-2's effects on male sexual behavior, whereas ERE-independent ER alpha signaling may mediate E-2's inhibitory effects on T production.

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Accession: 053043723

Download citation: RISBibTeXText

PMID: 17673514

DOI: 10.1210/en.2007-0673


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