Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary

Citation
Y. Ikeda et al., Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary, DEV DYNAM, 221(4), 2001, pp. 443-453
Citations number
48
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Cell & Developmental Biology
Journal title
DEVELOPMENTAL DYNAMICS
ISSN journal
1058-8388 → ACNP
Volume
221
Issue
4
Year of publication
2001
Pages
443 - 453
Database
ISI
SICI code
1058-8388(200108)221:4<443:NEEISI>2.0.ZU;2-Q
Abstract
Treatment of newborn female rats with estrogens significantly inhibits the growth and differentiation of the ovary. To understand the molecular mechan ism of estrogen action in the induction of abnormal ovary, we examined the expression profiles of steroidogenic factor 1 (SF-1) and several of its tar get genes in the developing ovaries after neonatal exposure to synthetic es trogen, estradiol benzoate (EB) by using reverse transcriptase polymerase c hain reaction, in situ hybridization, and immunohistochemistry. Morphologic examination indicated inhibitory effects of estrogen on the stratification of follicles and development of theca and interstitial gland during postna tal ovarian differentiation. The expression of the steroidogenic acute regu latory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 ( P450(SCC)), which are both essential for steroid biosynthesis, markedly dec reased in theca and interstitial cells throughout the postnatal development of the EB-treated ovary. However, expression of the transcriptional activa tor of the two genes, SF-1 was unaffected in theca and interstitial cells, although the number of these cells was lower in the EB-treated ovary than i n the control ovary. The expression of the estrogen mediator, estrogen rece ptor-alpha (ER-alpha), diminished specifically in theca cells at P6 and rec overed by P14 in the EB-treated ovary. These results indicate that the effe ct of estrogens is mediated by means of ER-alpha resulting in the down-regu lation of StAR and P450(SCC) genes during early postnatal development of th e ovary. These results suggest that the abnormal ovarian development by neo natal estrogen treatment is closely correlated with the reduced steroidogen ic activity, and the data obtained by using this animal model may account i n part the mechanism for aberrant development and function of the ovary in prenatally estrogen-exposed humans. (C) 2001 Wiley-Liss, Inc.