Pituitary Regulation: Three Key Hormones
The anterior pituitary controls the ovaries via three hormones, each with specific target cells and morphogenetic effects:
- FSH (follicle-stimulating hormone) acts on follicular cells. It initiates the growth of the primordial and secondary follicle pool, supports their development, and stimulates the enzyme aromatase.
- LH (luteinizing hormone) acts on theca (interstitial) cells. It triggers ovulation, ensures the transformation of the follicle into the corpus luteum, and stimulates androgen production, which is indirectly required for estrogen synthesis.
- Prolactin (luteotropic hormone) acts on the luteal cells of the corpus luteum, stimulating progesterone production and exerting a supportive trophic effect on ovarian structures.
The "Two-Cell Theory" of Estrogen Synthesis
The core concept of steroid biosynthesis in the growing follicle relies on cooperation between two cell types.
- First step (in theca cells): Stimulated by LH, these cells uptake cholesterol and convert it first into progesterone and then into testosterone.
- Second step (in follicular/granulosa cells): Testosterone diffuses across the basement membrane from the theca into the follicular layer. Here, driven by FSH, the enzyme aromatase (utilizing $H_2O$) converts androgens into estradiol.
Produced estrogens partially accumulate in the follicular fluid, creating a nourishing environment for the oocyte, and partially diffuse back across the basement membrane into the bloodstream.
Histological Analogy with the Male Reproductive System
Comparing the structures of the ovary and testis clearly demonstrates the homology of cell functions across sexes:
- Leydig cells (testis) and theca cells (ovary) are interstitial and responsible for testosterone synthesis.
- Sertoli cells (testis) and follicular cells (ovary) are capable of converting testosterone into estradiol.
Peptide Regulation and Follicular Atresia
Follicular cells synthesize not only steroids but also the protein hormone gonadocrinin. It accumulates in the follicular fluid and induces the death (atresia) of neighboring follicles, assisting in the selection of the dominant follicle, or triggers atresia of the follicle itself if ovulation is disrupted.
Atresia is accompanied by a shift in the pattern of hormonal secretion:
- In the early stage, while follicular cells remain viable, the atretic follicle serves as a major source of estrogen synthesis.
- In the late stage, follicular cells die, and atretic bodies form from the derivatives of the theca. Secretion shifts toward androgens and progesterone.
Note: At the onset of the menopausal transition, the mass maturation of primordial follicles (formation of the theca interna) and their subsequent massive atresia cause a sharp surge of estrogens and androgens. Over time, falling estrogen production against a background of preserved androgen synthesis by the ovaries and adrenal cortex can lead to virilization/masculinization.
Biosynthesis in the Corpus Luteum and Feedback
When a follicle transforms into a corpus luteum, a genetic switch occurs. In the follicular cells—which become luteal cells—the genes for aromatase enzymes are turned off, and the genes for the initial steps of biosynthesis are turned up. Consequently, luteal cells (under prolactin stimulation) halt at the stage of converting cholesterol to progesterone.
Ovarian estrogens and progesterone regulate their own production via negative feedback. They act on neurons in the limbic system, signaling the hypothalamus to decrease gonadotropin-releasing hormone (GnRH) production.
- Estrogens inhibit FSH secretion, keeping it suppressed almost throughout the entire cycle.
- Progesterone inhibits LH secretion, suppressing it during the second half of the cycle.
This prevents the development of new follicles during the current cycle.