Transcriptional Regulation of Ovarian Steroidogenic Genes: Recent Findings Obtained from Stem Cell-Derived Steroidogenic Cells

Figure 3

Regulation of granulosa cell differentiation by DAX-1 and PGC-1α via SF-1/Ad4BP and LRH-1. (a) During follicular development, the activities of SF-1/Ad4BP, LRH-1, and PGC-1α are repressed by DAX-1 in undifferentiated granulosa cells. Therefore, transcription of steroidogenic genes hardly occurred. (b) Gonadotropin induces the differentiation of granulosa cells into progesterone-producing cells. At this time, PGC-1α is released from DAX-1-mediated suppression via its reduction. This PGC-1α activation induces SF-1/Ad4BP and LRH-1. In particular, LRH-1 is highly induced by positive-feedback loop. Then, NR5A family proteins couple with PGC-1α to induce steroidogenic genes, such as StAR, CYP11A1, 3-HSD, and SR-BI.

(a) Before differentiation

(b) After gonadotropin stimulation