Estrogens - Effects
The effects of estrogens result mainly from their interaction with nuclear receptors, genomic effects, leading to modifications of the transcription of certain genes. These receptors are present especially in female sexual organs but also in other organs like hypothalamus, pituitary gland, liver and bone. There are two types of estrogen receptors called alpha and beta having a specific tissue distribution
In addition to their genomic effects, estrogens, estradiol in particular, have fast nongenomic effects such as vasodilation which are explained by direct activation of potassium channels of the plasma membrane leading to an exit of potassium and a relaxation of vascular smooth fibers. An increase of NO release by estradiol is also possible.
One can distinguish two types of effects, sexual and metabolic effects
Sexual effects
- During sexual differentiation of the fetus: the estrogens do not play a determining physiological part in female sexual differentiation because without ovaries, the fetus takes a female phenotype. But from a pharmacological and toxicological point of view, estrogens taken during pregnancy can induce deleterious effects. In girls born from mothers treated during their pregnancy by diethylstibestrol, a synthetic estrogen, vaginal and cervical cancers have appeared in adulthood. The prescription of estrogens to pregnant women is contra-indicated.
- At puberty: estrogens cause the development of primary and secondary sexual characters (uterus,uterine tube, vagina, breasts) and modify general morphology with female distribution of adipose tissue and skin changes.. At puberty, estrogens accelerate growth, their effect on growth being probably potentiated by androgens.
- Adulthood , estrogens act primarily on the genital apparatus.
They prevent the involution of the sexual characters: after a bilateral ovariectomy, the involution of uterus, vagina and tubes is prevented by the administration of estrogens which tends to restore the integrity of the sexual organs
- On the uterus: they induce an intense cellular multiplication (mitoses) of the endometrium whose thickness increases, as well as a proliferation of the cells of the myometrium with increase in their contractility. They induce the synthesis of progesterone receptors.
The administration of estrogens followed by their discontinuation can elicit a menstruation known as estrogen withdrawal bleeding.
- On the uterine cervix: they induce the secretion of abundant and fluid cervical mucus which is favourable to the penetration of the spermatozoa into the uterus.
- On the vagina: they maintain the trophicity of the mucous membrane and its hydration while the surface cells become eosinophil and scale. The reduction of the estrogens after the menopause induces some atrophy of the mucous membrane and its hypovascularisation. Estriol could act preferentially on the vagina. The vaginal modifications are measured in rats by the keratinisation test called Allen and Doisy test.
- On the pituitary gland: estradiol reduces the release of gonadorelin (GnRH) and FSH and take part in the regulation of the hormonal cycle in women. However, in the middle of the cycle, estradiol, by positive pituitary feedback effect, induces the secretion of LH. At onset of menopause, when the ovarian secretion decreases, there is a pituitary overstimulation.
Notice
Another hormone, inhibin, which is a glycoprotein secreted by ovaries, placenta and testis, decreases also the secretion of FSH and, to a lesser degree, LH.
Metabolic effects
- Protein anabolic activity: which remains much lower than that of androgens, but which is however important. The combination of estrogens with very low doses of androgens could induce growth. But estrogens accelerate epiphyseal fusion and can reduce the final size; they are used in high dose to slow down the growth of girls whose size risks being excessive.
- Anti-osteoporotic effect: and this is one of the reasons for their prescription after the menopause.
- Cardiovascular protection: It is considered that in women before the menopause they reduce the frequency of cardiovascular events, myocardial infarction, stroke. This beneficial effect is partly explained by a decrease of lipoproteins LDL and an increase in the HDL but also by a vasodilation, in particular by opening of potassium channels.
- They modify the serum concentration of some coagulation factors: decrease that of fibrinogen, procoagulant factor, but also decrease anti-thrombin and protein S, anticoagulant factors.
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