# Ovarian Steroidogenesis and the Two-Cell Theory

> NEET-PG Obstetrics and Gynaecology notes on ovarian steroidogenesis and the two-cell theory, covering theca and granulosa roles, aromatase and PCOS androgens.

- Canonical URL: https://prepelephant.com/topics/neet-pg/obstetrics-and-gynaecology/ovarian-steroidogenesis-two-cell-theory
- Exam / course: NEET-PG · Subject: Obstetrics and Gynaecology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Williams Gynecology; Guyton and Hall Textbook of Medical Physiology
- How to cite: "Ovarian Steroidogenesis and the Two-Cell Theory", PrepElephant, https://prepelephant.com/topics/neet-pg/obstetrics-and-gynaecology/ovarian-steroidogenesis-two-cell-theory

## Direct answer

Two-cell steroidogenesis is the process in which theca cells make androgens under LH and granulosa cells convert them to oestradiol under FSH, so neither cell type makes oestrogen alone. Theca cells express CYP17, while granulosa cells express aromatase (CYP19A1), and this division of labour explains the ovarian steroid pattern. It also explains why the androgen excess of PCOS originates in the theca cells.

## What you must remember

- **Theca cells:** carry LH receptors and CYP17 (17α-hydroxylase and 17,20-lyase), making androstenedione and testosterone from cholesterol.
- **Granulosa cells:** carry FSH receptors and aromatase (CYP19A1), converting androstenedione to oestrone and testosterone to oestradiol.
- **StAR protein:** moves cholesterol into the mitochondrion, the rate-limiting step, where CYP11A1 cleaves the side chain to pregnenolone.
- **Missing enzyme:** granulosa cells lack CYP17, so they depend on theca-derived androgens as their substrate.
- **Oestradiol:** the dominant ovarian oestrogen, produced mainly by growing follicles in the follicular phase.
- **Progesterone:** luteinised granulosa cells of the corpus luteum make most of it after the LH surge.
- **PCOS:** excess LH and insulin drive theca androgen overproduction, causing hyperandrogenism and anovulation.
- **17α-hydroxylase deficiency:** blocks both cortisol and sex steroid synthesis, causing primary amenorrhoea with absent puberty, and hypertension with hypokalaemia.

## How the two cells divide the work

The two cell types cooperate across the follicle wall, and each supplies what the other cannot make. The table compares their receptors, enzymes and products, along with the clinical situation that each one explains.

| Feature | Theca cell | Granulosa cell |
|---|---|---|
| Gonadotropin receptor | LH | FSH |
| Key enzyme | CYP17 (17α-hydroxylase) | Aromatase (CYP19A1) |
| Main product | Androstenedione and testosterone | Oestrone and oestradiol |
| Substrate source | Cholesterol | Theca-derived androgens |
| Clinical link | Androgen excess in PCOS | Oestrogen-driven follicular growth |

Blocking aromatase raises androgen levels in the follicle, while blocking CYP17 removes androgen production altogether. Exam vignettes often test which of the two enzymes is missing, so the table is worth memorising.

In the follicular phase, FSH raises aromatase activity in granulosa cells, so oestradiol climbs as the dominant follicle matures, while the LH-driven theca androgen supply sets the upper limit on that conversion. After the LH surge, the luteinised granulosa cells switch to progesterone production, which is why the same cell type changes its output across the cycle.

## Where the exam tries to catch you

Two-cell questions usually hinge on which cell carries which enzyme.

- **Trap:** Thinking granulosa cells make androgens from cholesterol. — **Correct:** They lack CYP17 and depend on androgens supplied by theca cells as their substrate.
- **Trap:** Attributing PCOS hyperandrogenism to a granulosa aromatase defect. — **Correct:** Theca cells overproduce androgens under LH and insulin, and granulosa aromatase only converts them, so it is not the primary cause.
- **Trap:** Confusing 17α-hydroxylase deficiency with aromatase deficiency. — **Correct:** 17α-hydroxylase deficiency causes hypertension with absent sex steroids and no puberty, whereas aromatase deficiency causes androgen excess and virilisation.

## Frequently asked questions

### Which ovarian cells produce androgens?
Theca cells produce androgens such as androstenedione and testosterone, using CYP17 under LH stimulation. These androgens then pass to granulosa cells, which convert them to oestrogen.

### Why do granulosa cells depend on theca cells for oestrogen synthesis?
Granulosa cells express aromatase but lack CYP17, so they cannot make androgens from cholesterol. They rely on androgens from theca cells, which is the basis of the two-cell theory.

### Which enzyme converts androgens to oestrogen in the ovary?
Aromatase, encoded by CYP19A1, converts androstenedione to oestrone and testosterone to oestradiol in granulosa cells under FSH stimulation. Its activity largely decides how much androgen becomes oestrogen in the follicle.

### Why does PCOS cause hyperandrogenism?
PCOS causes hyperandrogenism mainly through theca cell overproduction driven by excess LH and insulin resistance. Granulosa aromatase converts some of this androgen, but the primary defect lies in the theca cells.