Research Paper Volume 12, Issue 7 pp 6089—6108

Estradiol-induced senescence of hypothalamic astrocytes contributes to aging-related reproductive function declines in female mice

Figure 6. A model of estradiol action on hypothalamic astrocytes involving the progesterone production on the basis of present results and previous findings. Circulating estradiol acts on astrocytes that regulate progesterone (PROG) synthesis to activate the cAMP-PKA pathway. PKA can phosphorylate cytochrome P450scc and 3β-HSD, which regulate PROG production. The activated PKA pathway can also increase the expression of CYPs genes, which participate in the process of estradiol metabolism. Metabolic products of estradiol, 2-OHE2 and 4-OHE2, exert strong oxidative stress on astrocytes. ER, i.e. estrogen receptor; CHOL, i.e.cholesterol.