Ovarian Function and Estrogen-Progesterone Physiology

Ovarian function comprises folliculogenesis, ovulation, and the production of the ovarian steroids estrogen and progesterone. Under the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), follicles grow and synthesize estrogen via a cooperation between theca and granulosa cells; after ovulation the corpus luteum produces progesterone, the hormone that prepares and maintains the secretory endometrium.

Definition

Ovarian function is the gonadotropin-regulated process of follicular development, ovulation, and corpus luteum formation, through which the ovary produces oocytes and secretes estrogen (chiefly during follicular growth) and progesterone (chiefly from the corpus luteum).

Scope

The topic covers the recruitment and selection of ovarian follicles, the two-cell, two-gonadotropin pathway of estrogen synthesis, the formation and function of the corpus luteum, and the production of estrogen and progesterone. It is a physiology reference topic and does not provide clinical guidance.

Core questions

• How are follicles recruited and selected for growth?
• How do theca and granulosa cells cooperate to synthesize estrogen?
• How is the corpus luteum formed and what does it secrete?
• How do ovarian steroids feed back on the hypothalamic-pituitary axis?

Key concepts

• Folliculogenesis and the resting follicle pool
• Theca and granulosa cells
• Two-cell, two-gonadotropin estrogen synthesis
• Aromatase
• Dominant follicle selection
• Corpus luteum and progesterone
• Estrogen and progesterone feedback

Key theories

Two-cell, two-gonadotropin model of estrogen synthesis

Ovarian estrogen production requires both cell types and both gonadotropins: LH stimulates theca cells to make androgen substrate, which granulosa cells aromatize to estrogen under FSH control, so neither cell can make estrogen efficiently alone.

Initial and cyclic follicle recruitment

Follicles leave the resting pool through gonadotropin-independent initial recruitment, but only cyclic, FSH-dependent recruitment in each cycle rescues a cohort from atresia, from which a dominant follicle is selected.

Mechanisms

Primordial follicles are continuously recruited from the resting pool independently of gonadotropins, but each cycle a cohort is rescued from atresia by rising FSH (cyclic recruitment), from which one dominant follicle is selected (McGee & Hsueh, 2000). Within the growing follicle, LH stimulates theca cells to produce androgens, which diffuse to the granulosa cells where FSH-induced aromatase converts them to estradiol; this two-cell, two-gonadotropin cooperation accounts for follicular estrogen output (Hillier et al., 1994). The mid-cycle LH surge triggers ovulation and luteinization of the ruptured follicle; the resulting corpus luteum secretes progesterone, which dominates the luteal phase and supports a secretory endometrium (Mihm et al., 2011). Estrogen and progesterone feed back on the hypothalamus and pituitary, predominantly negatively, with estrogen exerting positive feedback to generate the ovulatory surge.

Clinical relevance

These mechanisms underlie understanding of ovulation, fertility, and the hormonal phases of the female reproductive cycle. The entry is educational reference on ovarian physiology; it is non-prescriptive and is not a basis for diagnosis or treatment.

History

The two-cell, two-gonadotropin concept of ovarian estrogen synthesis emerged from studies of theca and granulosa cell cooperation and was consolidated as a model of follicular oestrogen production (Hillier et al., 1994). Work on follicle dynamics distinguished gonadotropin-independent initial recruitment from cyclic, FSH-dependent recruitment and dominant-follicle selection (McGee & Hsueh, 2000), refining the physiological account of folliculogenesis.

Key figures

• Stephen Hillier
• Aaron Hsueh
• Eric McGee

Seminal works

• hillier-1994
• mcgee-2000

Frequently asked questions

Why does estrogen synthesis need two cell types?

Theca cells make androgen precursors under LH but cannot aromatize them efficiently, while granulosa cells have FSH-induced aromatase but limited substrate; estrogen is produced when the two cooperate, the two-cell, two-gonadotropin model.

What does the corpus luteum do?

After ovulation the ruptured follicle becomes the corpus luteum, which secretes progesterone to support the secretory endometrium during the luteal phase of the cycle.