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.