Estrogens (estradiol, estrone, estriol)
Also known as: oestrogen, estradiol, oestradiol, E2, estrone, estriol
C18 steroids — chiefly estradiol from ovarian granulosa cells — that drive female sexual development, proliferation of the endometrium, the mid-cycle LH surge and the maintenance of bone, and act in both sexes on bone, brain and liver.
Overview
Synthesis follows the two-cell, two-gonadotropin model: LH stimulates theca interna cells to make androstenedione from cholesterol; it diffuses into granulosa cells, where FSH-induced aromatase (CYP19A1) converts it to estrone and then (17β-HSD) to estradiol (E2), the most potent and main premenopausal estrogen. Estrone (E1) is formed by aromatisation in adipose tissue and is the main estrogen after menopause; estriol (E3) is the dominant estrogen of pregnancy, made by the placenta from fetal adrenal DHEA-S (the fetoplacental unit).
Estrogens act mainly through nuclear estrogen receptors ERα and ERβ (plus the membrane receptor GPER). Reproductive actions: growth of the uterus, tubes and vagina; proliferative phase of the endometrium and induction of progesterone receptors; thin, abundant, stretchy cervical mucus at ovulation; vaginal epithelial maturation (glycogen → lactobacilli → acidic pH); ductal growth of the breast; increased tubal motility and myometrial oxytocin receptors. Feedback: negative on GnRH/FSH/LH for most of the cycle, but positive when estradiol stays high (≈≥200 pg/mL for ≈36–48 h), producing the LH surge. Systemic actions: pubertal growth spurt and epiphyseal closure (in both sexes), maintenance of bone mass (reduced osteoclast activity), female fat distribution, favourable lipids (↑HDL, ↓LDL), and increased hepatic synthesis of binding globulins (SHBG, TBG, CBG), angiotensinogen and clotting factors — hence thrombotic risk with oral estrogen.
- Location
Source: ovarian granulosa cells (follicular phase) and corpus luteum; placenta (pregnancy); adipose tissue aromatisation (postmenopause and in men). Targets: uterus, cervix, vagina, breast, bone, brain, liver, blood vessels.
Function
- Development of female secondary sexual characteristics at puberty.
- Proliferation of the endometrium; induction of progesterone receptors.
- Positive feedback that triggers the LH surge and ovulation.
- Maintenance of bone density and epiphyseal closure (both sexes).
- Hepatic protein synthesis and favourable lipid profile.
- Physiology
Class: C18 steroids. Receptors: ERα, ERβ (nuclear), GPER (membrane). Bound to SHBG and albumin. Key enzyme: aromatase.
- Regulation
FSH (aromatase) and LH (theca androgen supply) stimulate ovarian synthesis; estradiol feeds back negatively on GnRH/FSH/LH except at mid-cycle (positive feedback). Placental estriol depends on fetal adrenal and liver function.
Clinical significance
Estrogen deficiency
Menopause, premature ovarian insufficiency, Turner syndrome, functional hypothalamic amenorrhoea: vasomotor symptoms, genitourinary syndrome of menopause (vaginal atrophy, dyspareunia, recurrent UTIs), osteoporosis and increased cardiovascular risk.
Unopposed estrogen and cancer
Estrogen without progesterone (anovulation in PCOS, obesity, estrogen-only HRT with a uterus, granulosa-cell tumours) causes endometrial hyperplasia and endometrioid adenocarcinoma. ER-positive breast cancers are treated with tamoxifen (a SERM — antagonist in breast, partial agonist in endometrium and bone) or aromatase inhibitors (letrozole, anastrozole).
Gynaecomastia
An increased estrogen:androgen ratio in men — puberty, cirrhosis (reduced clearance, increased aromatisation), Klinefelter syndrome, drugs (spironolactone, anabolic steroids), hCG-secreting tumours.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.