A calcium-induced calcium release mechanism supports luteinizing hormone-induced testosterone secretion in mouse Leydig cells

Autor(es)

Costa, Roberta Ribeiro ^[1] ; Varanda, Wamberto Antonio ^[1] ; Franci, Celso Rodrigues ^[1]

Afiliação do(s) autor(es)

^[1] Ribeirao Preto USP, Dept Physiol, Sch Med, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 299, n. 2, p. C316-C323, AUG 2010.
• Citações Web of Science: 20

Resumo

Costa RR, Varanda WA, Franci CR. A calcium-induced calcium release mechanism supports luteinizing hormone-induced testosterone secretion in mouse Leydig cells. Am J Physiol Cell Physiol 299: C316-C323, 2010. First published June 2, 2010; doi: 10.1152/ajpcell.00521.2009.-Leydig cells are responsible for the synthesis and secretion of testosterone, processes controlled by luteinizing hormone (LH). Binding of LH to a G protein-coupled receptor in the plasma membrane results in an increase in cAMP and in intracellular Ca(2+) concentration ({[}Ca(2+)](i)). Here we show, using immunofluorescence, that Leydig cells express ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs). Measurements of intracellular calcium changes using the fluorescent calcium-sensitive dye fluo-3 and confocal microscopy show that both types of receptors are involved in a calcium-induced calcium release (CICR) mechanism, which amplifies the initial Ca(2+) influx through plasma membrane T-type calcium channels (Ca(V)3). The RyRs and IP(3)Rs are functional, as judged from both their activation by caffeine and IP(3) and block by ryanodine and 2-aminoethoxydiphenyl borate (2-APB), respectively. RyRs are the principal players involved in the release of Ca(2+) from the endoplasmic reticulum, as evidenced by the fact that global Ca(2+) changes evoked by LH are readily blocked by 100 mu M ryanodine but not by 2-APB or xestospongin C. Finally, steroid production by Leydig cells is inhibited by ryanodine but not by 2-APB. These results not only broaden our understanding of the role played by calcium in Leydig cells but also show, for the first time, that RyRs have an important role in determining testosterone secretion by the testis. (AU)

• Processo FAPESP: 04/08868-0 - Consolidação do Centro de Microscopia Funcional do Campus da USP/ Ribeirão Preto
• Beneficiário: Roy Edward Larson
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 06/50954-7 - Correntes iônicas e receptores na fisiologia de células excitáveis e não excitáveis
• Beneficiário: Wamberto Antonio Varanda
• Modalidade de apoio: Auxílio à Pesquisa - Temático