The effects of estrogen on the expression of genes underlying the differentiation of somatic cells in the murine gonad.
Estrogen (17beta-estradiol, E2)-deficient aromatase knockout (ArKO) mice develop Sertoli and Leydig cells at puberty. We hypothesized that estrogen, directly or indirectly, regulates genes responsible for somatic cell differentiation and steroidogenesis. ArKO ovaries expressed estrogen receptors alpha and beta, and LH receptor, indices of estrogen responsiveness in the ovary. Wild-type (Wt) and ArKO mice received either E2 or placebo for 3 wk, from 7-10 wk of age. E2 decreased serum FSH and LH and increased uterine weights of 10-wk-old ArKO mice. We measured mRNA expression of Sertoli cell, Sry-like HMG box protein 9 (Sox9); three upstream transcription factors, liver receptor homolog-1 (Lrh-1), steroidogenic factor 1, and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1; and one downstream factor, Müllerian-inhibiting substance. Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and 17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. In conclusion, the expression of the genes regulating somatic cell differentiation is directly or indirectly responsive to estrogen.
Britt
Kara L
KL
Prince Henry's Institute of Medical Research, Monash Medical Centre Clayton, Clayton, Victoria 3168, Australia. kara.britt@phimr.monash.edu.au.
Stanton
Peter G
PG
Misso
Marie
M
Simpson
Evan R
ER
Findlay
Jock K
JK
D000818:Animals; D001141:Aromatase / Q000502:physiology; D002454:Cell Differentiation; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000166:cytology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013739:Testosterone / Q000097:blood
D004967:Estrogens; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006913:Hydroxysteroid Dehydrogenases; C035507:3(17)-hydroxysteroid dehydrogenase; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase