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Mol Endocrinol ; 23(3): 349-59, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19131510

RESUMO

Previously, we have reported that 17beta-estradiol (E(2)) induces an increase in firing activity of primate LH-releasing hormone (LHRH) neurons. The present study investigates whether E(2) alters LHRH release as well as the pattern of intracellular calcium ([Ca(2+)](i)) oscillations and whether G protein-coupled receptor 30 (GPR30) plays a role in mediating the rapid E(2) action in primate LHRH neurons. Results are summarized: 1) E(2), the nuclear membrane-impermeable estrogen, estrogen-dendrimer conjugate, and the plasma membrane-impermeable estrogen, E(2)-BSA conjugate, all stimulated LHRH release within 10 min of exposure; 2) whereas the estrogen receptor antagonist, ICI 182,780, did not block the E(2)-induced LHRH release, E(2) application to cells treated with pertussis toxin failed to induce LHRH release; 3) GPR30 mRNA was expressed in olfactory placode cultures, and GPR30 protein was expressed in a subset of LHRH neurons; 4) pertussis toxin treatment blocked the E(2)-induced increase in [Ca(2+)](i) oscillations; 5) knockdown of GPR30 in primate LHRH neurons by transfection with small interfering RNA (siRNA) for GPR30 completely abrogated the E(2)-induced changes in [Ca(2+)](i) oscillations, whereas transfection with control siRNA did not; 6) the estrogen-dendrimer conjugate-induced increase in [Ca(2+)](i) oscillations also did not occur in LHRH neurons transfected with GPR30 siRNA; and 7) G1, a GPR30 agonist, resulted in changes in [Ca(2+)](i) oscillations, similar to those observed with E(2). Collectively, E(2) induces a rapid excitatory effect on primate LHRH neurons, and this rapid action of E(2) appears to be mediated, in part, through GPR30.


Assuntos
Estradiol/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Neurônios/efeitos dos fármacos , Primatas , Receptores Acoplados a Proteínas G/fisiologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , Dendrímeros/farmacologia , Embrião de Mamíferos , Estradiol/análogos & derivados , Estrogênios Conjugados (USP)/farmacologia , Feminino , Fulvestranto , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Macaca mulatta , Neurônios/metabolismo , Condutos Olfatórios/efeitos dos fármacos , Condutos Olfatórios/metabolismo , Toxina Pertussis/farmacologia , Gravidez , Primatas/metabolismo , Primatas/fisiologia , RNA Interferente Pequeno/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Soroalbumina Bovina/farmacologia , Transmissão Sináptica/efeitos dos fármacos
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