Estrogen is a class of hormones that are produced by the ovaries in women and by other tissues in both sexes. They are responsible for the development and maintenance of the female reproductive system and secondary sex characteristics. Estrogens also have important non-reproductive roles, such as regulating bone growth and maintaining brain function.
The main estrogen in women is 17β-estradiol, which is produced primarily by the granulosa cells of the ovary during follicular maturation. Smaller amounts of estrone and estriol are also present in circulation. The levels of all three estrogens fluctuate throughout the menstrual cycle, with highest levels occurring just before ovulation. During pregnancy, circulating levels of estrogen increase dramatically, peaking near the end of the first trimester. After menopause, production of ovarian estrogens ceases entirely and circulating levels decline sharply. However, small amounts of estrogen continue to be produced by adipose tissue throughout postmenopausal life.
In men, testosterone is converted to estrogen by aromatase enzymes present in various tissues including adipose tissue, muscle, and skin . This conversion results in low but significant circulating levels of estrone and 17β-estradiol in men. As with women, these levels fluctuate throughout the day but remain relatively constant over time .
The biological effects of estrogen are mediated via its binding to two types of receptors: nuclear receptors (NRs) located within cells ,and membrane receptors (mERs) found on cell surfaces . NRs include both ligand-dependent transcription factors (ERα and ERβ) that regulate gene expression , as well as orphan NRs that lack known ligands but may still be involved in mediating some estrogenic effects . mERs include G protein-coupled receptors (GPR30/GPER1 ) as well as receptor tyrosine kinases (RYK) . Ligand binding to either typeof receptor resultsin activationof different signaling pathways that ultimately leadto changesin gene expression or other cellular responses . In additionto its actionsthrough specificreceptors ,estrogen canalso influencecellular responses indirectlyby modulatingthe activityof other signaling moleculessuch askinasesor transcription factors not directly under its control .