Estrogens (AmE), oestrogens (BE), or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal. Their name comes from the Greek words estrus/οίστρος = sexual desire + gen/γόνο = to generate.
Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors which in turn modulate the expression of many genes. Additionally, estrogens have been shown to activate a G protein-coupled receptor, GPR30.
Estrone is produced during menopause, estradiol is the predominant form in nonpregnant females, and estriol is the primary estrogen of pregnancy. In the body these are all produced from androgens through actions of enzymes.
- From menarche to menopause the primary estrogen is estradiol. In postmenopausal women the primary estrogen is estrone.
- The enzyme aromatase converts testosterone to estradiol. Aromatase also converts androstenedione to estrone.
- Estrone is weaker than estradiol.
Premarin, a commonly prescribed estrogenic drug, contains the steroidal estrogens equilin and equilenin. There are oestradiol skin patches such as Estraderm (the original brand, introduced in the late 1980s) that offer a completely natural alternative. (A skin patch rather than pill also has the advantage of direct transmission into the blood stream without going through the liver.)
A range of synthetic and natural substances have been identified that also possess estrogenic activity.
- Synthetic substances of this kind are known as xenoestrogens.
- Plant products with estrogenic activity are called phytoestrogens.
- Those produced by fungi are known as mycoestrogens.
Unlike estrogens produced by mammals, these substances are not necessarily steroids.
Steroidogenesis, showing estrogens at bottom right as in pink triangle.
Estrogens are produced primarily by developing follicles in the ovaries, the corpus luteum, and the placenta. Luteinizing hormone (LH) stimulates the production of estrogen in the ovaries. Some estrogens are also produced in smaller amounts by other tissues such as the liver, adrenal glands, and the breasts. These secondary sources of estrogens are especially important in postmenopausal women. Fat cells also produce estrogen, potentially the reason why being underweight or overweight are risk factors for infertility.
In females, synthesis of estrogens starts in theca interna cells in the ovary, by the synthesis of androstenedione from cholesterol. Androstenedione is a substance of moderate androgenic activity. This compound crosses the basal membrane into the surrounding granulosa cells, where it is converted to oestrone or oestradiol, either immediately or through testosterone. The conversion of testosterone to oestradiol, and of androstenedione to oestrone, is catalyzed by the enzyme aromatase.
Oestradiol levels vary through the menstrual cycle, with levels highest just before ovulation.
The actions of estrogen are mediated by the Estrogen receptor (ER), a dimeric nuclear protein that binds to DNA and controls gene expression. Like other steroid hormones, estrogen enters passively into the cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences called a Hormone response element to activate the transcription of some 137 ER-regulated genes, of which 89 are direct target genes.  Since estrogen enters all cells, its action are dependent on the presence of the ER in the cell. The ER is expressed in specific tissues including the ovary, uterus and breast.
While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sexual characteristics, such as breasts, and are also involved in the thickening of the endometrium and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the reproductive system important to the maturation of sperm and may be necessary for a healthy libido. Furthermore, there are several other structural changes induced by estrogen in addition to other functions.
- promote formation of female secondary sex characteristics
- accelerate metabolism
- reduce muscle mass
- increase fat stores
- stimulate endometrial growth
- increase uterine growth
- increase vaginal lubrication
- thicken the vaginal wall
- maintenance of vessel and skin
- reduce bone resorption, increase bone formation
- morphic change (endomorphic -> mesomorphic -> ectomorphic) protein synthesis
- increase hepatic production of binding proteins
- Fluid balance
- Gastrointestinal tract
- Lung function
In mice, estrogens (which are locally aromatized from androgens in the brain) play an important role in psychosexual differentiation, for example, by masculinizing territorial behavior; the same is not true in humans. In humans, the masculinizing effects of prenatal androgens on behavior (and other tissues, with the possible exception of effects on bone) appear to act exclusively through the androgen receptor. As a result, the utility of rodent models for studying human psychosexual differentiation has been questioned.
Estrogen is considered to play a significant role in women’s mental health. Sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained estrogen low levels correlates with significant mood lowering. Clinical recovery from postpartum, perimenopause, and postmenopause depression has been shown to be effective after levels of estrogen were stabilized and/or restored.
Low estrogen levels in male lab mice may be one cause of obsessive–compulsive disorder (OCD). When estrogen levels were raised through the increased activity of the enzyme aromatase in male lab mice, OCD rituals were dramatically decreased. Hypothalamic protein levels in the gene COMT are enhanced by increasing estrogen levels which is believed to return mice that displayed OCD rituals to normal activity. Aromatase deficiency is ultimately suspected which is involved in the synthesis of estrogen in humans and has therapeutic implications in humans having obsessive-compulsive disorder.
Since estrogen circulating in the blood can negatively feed-back to reduce circulating levels of FSH and LH, most oral contraceptives contain a synthetic estrogen, along with a synthetic progestin. Even in men, the major hormone involved in LH feedback is estradiol, not