Estrogens: Physiology and Effects

Mechanism of action at the cellular level

Sex steroids exert their effects through specific receptors. There are two types of receptors in target cells: cytoplasmic (strictly specific to estrogens, progesterone, and testosterone) and nuclear.

The interaction of estrogens with a cell occurs in several stages:

1. The steroid hormone penetrates inside the target cell.
2. It binds to a specific cytoplasmic receptor.
3. The resulting hormone-receptor complex is transported into the cell nucleus.
4. The complex binds to chromatin.
5. Through the activation of DNA and RNA, the synthesis of specific proteins is initiated, which provide the final physiological response.

Synthesis and local reproductive effects

In females, the main source of estrogens (estradiol, estrone, estriol) is the follicular cells (granulosa) of maturing ovarian follicles. In males, a small amount of estrogens is synthesized by interstitial Leydig cells and is also produced in Sertoli cells via aromatization (conversion) of testosterone.

At the ovarian level, estrogens stimulate the proliferation of follicular cells, prevent the degeneration (atresia) of the dominant follicle, and induce the expression of new follicle-stimulating hormone (FSH) receptors.

In the uterus, they are responsible for the proliferative phase of the uterine cycle — active restoration of the functional layer of the endometrium after its rejection. In addition, estrogens ensure the maturation of female reproductive organs and stimulate the development of the duct system and stromal component of the mammary glands.

Systemic effect on the body

Estrogens affect many tissues that have receptors for them (including the myocardium, endothelium, and vascular smooth muscle cells):

• Bone system: initiate the closure of epiphyseal growth plates (stop longitudinal bone growth) and maintain normal remodeling, preventing the destruction (resorption) of bone tissue.
• Skin and appendages: activate collagen production, preserving skin elasticity.
• Metabolism and adipose tissue: shape the female phenotype of adipose tissue distribution, participate in the regulation of the lipid profile, calcium metabolism, and maintain the blood clotting system (hemostasis).
• Central nervous system: acting on receptors in the hippocampus (emotion regulation) and autonomic centers, estrogens participate in the formation of the "menstrual wave" phenomenon — physiological fluctuations in nervous system tone and mood during premenstrual days.

Estrogens and functional diagnostics tests

Estrogen levels change throughout a normal 28-day cycle. In the follicular phase, their concentration rises, peaking before ovulation (on the 14th day). This is clearly reflected in functional diagnostics tests:

• Pupil sign: reflects the degree of gaping of the external os of the uterine cervix and the amount of mucus. During ovulation, at the peak of estrogens, this sign is maximally expressed.
• Crystallization sign (fern phenomenon): the ability of cervical mucus to form crystals upon drying directly depends on estrogen levels. By ovulation, crystallization reaches its maximum.
• Karyopyknotic index (KPI): shows the percentage of superficial cells in a vaginal smear with pyknotic nuclei (a marker of estrogen saturation). In the early phase, it is 20–40%, and during ovulation, it rises to 80–88%.

Class and exam questions

What else to study on this topic

• Phases of the uterine and ovarian cycles
• Physiological effects of progesterone and androgens
• The "menstrual wave" phenomenon and the role of the central nervous system
• Mechanism of the thermogenic action of progesterone
• Endocrine function of male gonads

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.