Regulatory mechanism of aromatase and '2-cell, 2-gonadotropin hypothesis'. The left panel illustrates that follicles are mainly composed of oocytes, granulosa cells and theca cells. Androstenedione and androsterone secreted by theca cells penetrate into granulosa cells and are converted into estrone and estradiol by the aromatase in granulosa cells under the stimulation of FSH and LH hormones. A small part acts on the ovaries, and the majority is released into the blood, collectively referred to as the '2-cell, 2-gonadotropin hypothesis'. The right panel mainly introduces the regulatory mechanism of aromatase in granulosa cells. FSH and LH bind to receptors and regulate CYP19A1 through PKA pathway. At the same time, IGF-1 binds to its receptor to activate PI3K/Akt, which upregulates the expression of CYP19; T3 cooperates with FSH also to acts on aromatase via PI3K/AKT pathway. The inhibition of the hormone-stimulated ERK with PD98059 can act on c-fos, causing the upregulation of CYP19 and the downregulation of CYP17. LH, luteinizing hormone; FSH, follicle-stimulating hormone; ERK, extracellular signal-regulated kinase; PI3K, phosphoinositide 3-kinase; PKA, protein kinase A; cAMP, cyclic adenosine monophosphate; CEBPB, CCAAT/enhancer-binding protein beta.