Differential role of the estrogen receptors ESR1 and ESR2 on the regulation of proteins involved with proliferation and differentiation of Sertoli cells from 15-day-old rats.
The aim of the present study was to investigate the role of each estrogen receptors on the regulation of proteins involved with proliferation and differentiation of Sertoli cells from 15-day-old rats. Activation of ESR1 by 17β-estradiol (E2) and ESR1-selective agonist PPT increased CCND1 expression, and this effect was dependent on NF-kB activation. E2 and the ESR2-selective agonist DPN, but not PPT, increased, in a PI3K and CREB-dependent manner, the expression of CDKN1B and the transcription factors GATA-1 and DMRT1. Analyzing the expression of ESR1 and ESR2 in different stages of development of Sertoli cells, we observed that the ESR1/ESR2 ratio decreased with age, and this ratio seems to be important to determine the end of cell proliferation and the start of cell differentiation. In Sertoli cells from 15-day-old rats, the ESR1/ESR2 ratio favors the effect of ESR1 and the activation of this receptor increased [Methyl-(3)H]thymidine incorporation. We propose that in Sertoli cells from 15-day-old rats E2 modulates Sertoli cell proliferation through ESR1/NF-kB-mediated increase of CCND1, and cell cycle exit and differentiation through ESR2/CREB-mediated increase of CDKN1B, GATA-1 and DMRT1. The present study reinforces the important role of estrogen for normal testis development.
Section of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de maio 100, INFAR, Vila Clementino, São Paulo, SP 04044-020, Brazil.
Thaís F G
TFG
Lucas
Section of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de maio 100, INFAR, Vila Clementino, São Paulo, SP 04044-020, Brazil.
Maria Fatima M
MFM
Lazari
Section of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de maio 100, INFAR, Vila Clementino, São Paulo, SP 04044-020, Brazil. Electronic address: csporto@unifesp.br.
Catarina S
CS
Porto
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D011422:Propionates
D017362:Cyclic AMP Response Element-Binding Protein; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D050982:GATA1 Transcription Factor; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; D013936:Thymidine; D014157:Transcription Factors; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C110547:DMRT1 protein; C000606206:Nfkbia protein, rat; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
CCND1; CDKN1B; DMRT1; Estrogen receptors; GATA-1; Sertoli cells