抄録
Estrogen binds the estrogen receptor (ER), and the subsequent regulation of gene transcription is called the slow genomic mode of estrogen action. In contrast, rapid, non-genomic actions of estrogen initiated at the membrane also exist. Though the genomic actions of estrogen have been more prominent, both rapid and slow modes of action are important in reproduction. Using a two-pulse paradigm, we have shown that a first pulse of a membrane-limited estrogen conjugate (E2-BSA) rapidly initiates non-genomic actions and potentiates transcription induced by a subsequent pulse of 17β-estradiol from a consensus estrogen-response element (ERE) driven reporter gene in neuroblastoma cells, transfected with ERα. In these cells, we have shown that rapid effects that are important to this transcriptional potentiation by E2-BSA include kinase activation and calcium flux. In addition, we show that these actions are initiated via a Gαq-coupled receptor at the membrane and may involve βγ signaling to the protein kinase B pathway. Behaviorally, pulsatile estradiol benzoate (EB) administration to ovariectomized female rats induces lordosis behavior comparable to a single continuous administration of EB. Infusion of E2-BSA into the ventromedial hypothalamus could potentiate lordosis behavior induced by EB, demonstrating the applicability of this paradigm in vivo. We are currently searching for endogenous estrogen-induced genes, relevant to reproduction, whose transcription is affected by E2-BSA. [J Physiol Sci. 2008;58 Suppl:S33]
