Ontogeny of Steroidogenesis in the Fetal Sheep Gonad1

Abstract

The aim of this study was to determine 1) the time of onset and cellular localization of gene expression for steroidogenic factor-1 (SF-1), steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase/Delta(5),Delta(4) isomerase (3beta-HSD), and the cytochrome P450 enzymes for cholesterol side-chain cleavage (P450(scc)), 17alpha-hydroxylase (P450(17alphaOH)), and aromatase (P450(arom)) during gonadal development; and 2) the amount of progesterone, androstenedione, testosterone, and 17beta-estradiol present in the fetal sheep gonad. Fetuses were collected on Days 24, 26, 28, 30, 32, 35, 40, 55, and 75 of gestation, and gene expression was determined by in situ hybridization. The steroid content of gonads collected on Days 30, 35, 55, and 75 of gestation was determined by RIA. Developing gonads collected from both male and female fetuses were steroidogenically active around the time of morphological sexual differentiation. In the female, the steroidogenic cells were initially located at the boundary of the cortex and medulla but become increasingly restricted to the mesonephric-derived cell streams. In the male, once tubules were identifiable, steroidogenesis was restricted to the interstitial regions. Interestingly, expression of both SF-1 and 3beta-HSD was observed prior to morphological sexual differentiation. In addition, expression of both of these genes was more widespread than the other genes in both males and females.

Disordered follicle development in ovaries of prenatally androgenized ewes

“…The presence of putative theca cells in the stroma surrounding medium-sized (and some small) preantral follicles has been suggested in a study of rat ovary (Hirshfield 1991) although, in rodents, the theca layer tends to form at an earlier stage of follicular development than in the ovine ovary (Fortune & Eppig 1979, Lundy et al 1999. Nevertheless, the presence of P450c17 has been demonstrated in both follicular and stromal tissues of the fetal sheep ovary, suggesting that the ovine ovary has the capacity to produce androgen in the absence of mature follicles (Quirke et al 2001).…”

Endocrinology of the mammalian fetal testis

“…In cases where fetal Leydig cells fail to develop, or androgen production is disrupted, pseudohermaphroditism will occur (Geissler et al 1994, Kremer et al 1995, Caron et al 1997, Clark et al 2000, Hu et al 2002. Transcripts encoding the critical enzymes required for androgen production can be detected in the testis shortly after Leydig cell differentiation (13.0 dpc in the mouse and 35 dpc in the sheep; Greco & Payne 1994, Quirke et al 2001, and testosterone can be detected at around 13.0 dpc in the mouse (Gondos 1980), 35 dpc in the sheep (Quirke et al 2001), and at 7 GW in the human, peaking in the human in the early second trimester (Tapanainen et al 1981, Fowler et al 2009, Scott et al 2009). INSL3 production by the fetal Leydig cells appears to be largely constitutive, and Insl3 transcripts are detectable in the mouse testis at about the same time as Leydig cell differentiation in the mouse (McKinnell et al 2005), and both INSL3 protein and transcript are clearly present in the male human fetus by the early second trimester (Anand-Ivell et al 2008, Bay et al 2008.…”

FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development

“…In sheep, ovaries are steroidogenically active at the time of morphological sexual differentiation as attested by direct hormonal dosages or CYP19 expression studies (Mauléon et al 1977, Payen et al 1996, Quirke et al 2001. Interestingly, in XX sex-reversed PIS / goat fetuses, the first affected gene following FOXL2 extinction is CYP19 (Pailhoux et al 2002.…”