In vivo regulation of Zif268 messenger RNA expression by 17 beta-estradiol in the rat uterus.
Administration of 17 beta-estradiol (E2) induces a mitogenic response in the rat uterus. Previous studies have shown that this effect involves the transient activation of c-fos and c-myc expression, followed by significant increases in both DNA synthesis and cell proliferation. Zif268 is a zinc finger-containing, DNA-binding transcription factor that has been implicated in the regulation of cell growth and development and has been shown to be coregulated with c-fos in a number of systems. To determine whether Zif268 is also a target for estrogen regulation, we measured the effects of E2 on Zif268 mRNA expression in the uterus of the ovariectomized rat. In this report we demonstrate that although low levels of Zif268 mRNA expression are detectable in the uteri from ovariectomized control rats, treatment with E2 (4, 40, or 400 micrograms/kg BW) induces a rapid and transient 45- to 50-fold increase in the level of Zif268 mRNA 2 h after E2 treatment. The elevated levels of Zif268 mRNA returned to basal 6 h after hormone treatment. Lower doses of E2 (0.004, 0.04, and 0.4 micrograms/kg) had little or no effect on Zif268 mRNA expression, while higher doses of E2 (4-400 micrograms/kg) resulted in maximal increases in Zif268 expression. Dexamethasone, 5 alpha-dihydrotestosterone, and progesterone had no effect on uterine Zif268 mRNA expression, and the induction of Zif268 by E2 was abolished by pretreating the animals with the RNA synthesis inhibitor actinomycin-D. In addition, stimulation of Zif268 mRNA expression was observed with the short-acting estrogen estriol, suggesting that the response may be specific for estrogenic steroids.(ABSTRACT TRUNCATED AT 250 WORDS)
Suva
L J
LJ
Department of Bone Biology and Osteoporosis Research Merck, Sharp, and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Harm
S C
SC
Gardner
R M
RM
Thiede
M A
MA
D000199:Actins / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D004958:Estradiol / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017874:Immediate-Early Proteins; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014599:Uterus / Q000187:drug effects / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics
D000199:Actins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D013196:Dihydrotestosterone; D003609:Dactinomycin; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D012313:RNA; D003907:Dexamethasone