17-beta-estradiol elicits genomic and non-genomic responses in mouse male germ cells.
Estrogens have been postulated to exert a detrimental effect on spermatogenesis in vivo. Since mouse male germ cells express estrogen receptors, we have investigated whether molecular pathways are activated by estrogen stimulation of these cells. Our results demonstrate that estrogen receptor beta is expressed in mitotic and meiotic male germ cells as well as in the spermatogonia derived GC-1 cell line. By using this cell line, we show that 17-beta-estradiol triggers activation of a transcriptional response that requires a functional estrogen receptor. Moreover, GC-1 cells respond to estrogens by transiently activating a signal transduction pathway that impinges on the mitogen-activated protein kinases (MAPK) ERK1 and -2. A similar dose-dependent transient activation of ERKs was also observed in primary mouse spermatocytes in culture. Activation by the estrogen was specific because other steroids such as progesterone and dihydrotestosterone were ineffective and because it could be blocked by the selective inhibitor of the ERK pathway and by competitive inhibitors of the estrogen receptor. Finally, we observed that 17-beta-estradiol does not affect spontaneous or induced apoptosis in cultured mouse spermatocytes, indicating that the apoptotic effects observed in vivo require additional testicular components.
Department of Histology and Medical Embriology, University of Rome La Sapienza, Rome, Italy.
Elena
E
Vicini
Maria
M
Loiarro
Silvia
S
Di Agostino
Serena
S
Corallini
Federica
F
Capolunghi
Rita
R
Carsetti
Paolo
P
Chieffi
Raffaele
R
Geremia
Mario
M
Stefanini
Claudio
C
Sette
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015533:Transcriptional Activation
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases