Activation of 'immediate-early' genes by estrogen is not sufficient to achieve stimulation of DNA synthesis in rat uterus.
17 beta-estradiol, a long acting estrogen that is mitogenic for rat uterus in vivo, or the short acting estrogens estriol and 16 alpha-estradiol, not mitogenic on their own, were injected into adult, castrated rats and their effect on uterine gene expression and rate of DNA synthesis were compared. All three compounds increased steady-state mRNA concentration of c-fos, c-jun and c-myc proto-oncogenes to comparable levels (2 hrs after treatment), whereas only 17 beta-estradiol was found to stimulate significantly DNA synthesis (20-22 hrs later). Based on the different retention time of the tested estrogens in rat tissues, it is concluded that a short exposure to the hormone is sufficient to render uterine cells competent to progress through the cell cycle, via activation of 'immediate-early' genes expression, but that stimulation of DNA synthesis requires further changes, achieved via a prolonged exposure of the cells to the estrogenic stimulus.
Persico
E
E
Istituto di Patologia Generale e Oncologia, Prima Facoltà di Medicina e Chirurgia, Università di Napoli, Italy.
Scalona
M
M
Cicatiello
L
L
Sica
V
V
Bresciani
F
F
Weisz
A
A
D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology*; D004964:Estriol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D010052:Ovariectomy; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014599:Uterus / Q000502:physiology*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D004958:Estradiol; D004247:DNA; D004964:Estriol