Theca Cells vs Granulosa Cells: Roles in Hormone Production

Estrogen in the ovary is a two-cell job. The theca cells on the outside of each egg follicle make the raw ingredient, and the granulosa cells on the inside finish it. Neither can produce estrogen alone, so researchers describe them as partners rather than separate factories. That split explains several things people run into in real life, from AMH fertility tests to the high testosterone seen in PCOS.

Where Theca and Granulosa Cells Sit in the Ovary

Each egg in the ovary sits in a fluid-filled sac called a follicle, wrapped in layers of support cells. As the follicle grows, the granulosa layers multiply and the fluid cavity enlarges. Usually only one follicle reaches ovulation each cycle.

Granulosa cells form the inner layer closest to the egg, and they have no blood vessels of their own.¹ A thin membrane separates them from the outer theca layer, where blood vessels grow from the secondary follicle stage onward.² So theca cells receive hormones and cholesterol straight from the blood, while granulosa cells depend on what passes through the membrane.

That membrane works more like a filter than a wall: small molecules such as androgens can pass, but the two layers stay distinct.

The pituitary gland releases two hormones that run the ovary: LH (luteinizing hormone) and FSH (follicle-stimulating hormone). The receptor for FSH is found only on granulosa cells.³ Theca cells carry the LH receptor and respond to LH by making androgens, male-type hormones.⁴ So the brain can steer each layer separately by changing how much LH versus FSH it sends.

How the Two Cells Team Up to Make Estrogen

Under LH, theca cells convert cholesterol into androgens such as androstenedione.⁵ They do this work because the enzyme needed for the key androgen-making step is made only in theca cells.⁶ LH raises both androstenedione output and the activity of that enzyme’s gene in theca cells.⁷

The androgens then diffuse across the membrane into granulosa cells.⁸ There, FSH makes the granulosa cells produce aromatase, the enzyme that converts androgens into estrogen, mainly estradiol.⁹ Theca cells have little to no aromatase, so they cannot finish the job themselves.¹⁰

An enzyme is a protein that carries out one chemical step, and each cell type carries only some of the enzymes needed for the full path from cholesterol to estradiol. Theca cells are equipped for the early steps that build androgens out of cholesterol. Granulosa cells are equipped for the last step, using the converting enzyme. Neither has the full toolkit, so the hormone moves from one to the other like a part going down an assembly line.

You can think of it as a relay race. Theca cells run the first leg and hand off androgen as the baton, and granulosa cells run the final leg to estradiol. If either runner is missing or slow, the race stalls, and LH and FSH act as the coaches signaling each one.

This also explains why women’s ovaries make androgens at all. Androgens are a normal ingredient, not a sign of a problem, and most theca androgen is meant to become estrogen.

The partnership boosts output, too. When the two cell types are grown together, they make far more estrogen than either produces alone.¹¹ The cells also trade growth signals in a loop, each prompting the other to make more of its signal.¹² In this way, granulosa cells can directly push theca cells to grow and make more hormone.¹³

Other Hormones Granulosa Cells Make, AMH and Inhibin

Granulosa cells produce two protein hormones, AMH (anti-Müllerian hormone) and inhibin.¹⁴ The granulosa cells of small, early follicles make large amounts of AMH.¹⁵ So blood AMH levels rise and fall with the number of small follicles in the ovaries.¹⁶ As follicles mature and make more estrogen under FSH, their AMH output drops.¹⁷

On a fertility report, AMH is often read as an estimate of how many small follicles remain, sometimes called ovarian reserve. It does not measure egg quality. A low AMH suggests fewer small follicles, which can mean a smaller response to fertility medication. It does not by itself mean a person cannot get pregnant naturally, since one good egg is all a cycle needs. A high AMH suggests many small follicles and often accompanies PCOS, but it is a clue rather than a diagnosis. Doctors interpret it alongside age and ultrasound follicle counts.

Inhibin travels to the pituitary and suppresses FSH release.¹⁸ Growing follicles use it to signal the brain that they are on track, and the brain eases off FSH so fewer follicles are recruited. That helps one follicle become dominant. Higher androgen levels inside a follicle push granulosa cells to make more AMH and less inhibin B.¹⁹

What Happens to Both Cells After Ovulation

After ovulation, the emptied follicle turns into a blood-rich structure called the corpus luteum.²⁰ Granulosa cells become large luteal cells and theca cells become small luteal cells.²¹ Both types carry LH receptors and make progesterone.²² So in the second half of the cycle, the former partners shift from an estrogen relay to joint progesterone production.

Progesterone prepares the uterine lining for a possible pregnancy. In a cycle without pregnancy, the corpus luteum works for roughly two weeks and then breaks down. Progesterone falls, and that drop triggers the period. The remnant shrinks into a small scar-like patch, and the next cycle’s follicles begin growing. Because progesterone peaks in the middle of this phase, doctors check mid-luteal progesterone to confirm that ovulation happened.

How Theca Cells Drive High Androgens in PCOS

In polycystic ovary syndrome (PCOS), the brain often sends too much LH relative to FSH. Excess LH drives theca cells to overproduce androgens.²³ Meanwhile the lower FSH weakens granulosa cells’ ability to convert those androgens to estrogen.²⁴ The relay breaks at the hand-off, and extra androgen spills into the blood.

Follicles stall for the same reason: they make too little estrogen to reach full maturity. Without the estrogen rise that normally helps trigger ovulation, a follicle often stops growing at a small size. Over time many small follicles accumulate, which shows up as a string of small follicles on ultrasound.

The theca cells themselves also differ. The LH to FSH imbalance makes theca cells multiply, adding more androgen-making cells.²⁵ Theca cells taken from polycystic ovaries made many times more androstenedione than normal theca cells, even without extra LH.²⁶ So PCOS androgen excess appears to come partly from a built-in difference in the theca cells, not only from brain signals.²⁷

Insulin adds fuel. Insulin and LH are thought to work together to push ovarian androgen production in PCOS.²⁸ Together they raise theca androstenedione output 3 to 4 times, more than either alone.²⁹ In obese mice, removing the insulin receptor from theca cells corrected high androgens and infertility.³⁰

For someone with PCOS, high androgens can cause acne, excess hair growth, and scalp hair thinning. Poor follicle maturation leads to irregular or missed periods. Blood tests may show high testosterone and high AMH, and ultrasound often shows many small follicles.

Lowering insulin removes one push on theca androgen output. Weight loss and medicines like metformin target insulin resistance, and some women see more regular cycles once their insulin levels improve. Options are best discussed with a doctor rather than tried alone.

Granulosa Cell Tumors and Their Hormone Signs

Adult granulosa cell tumors are rare, but they are the most common tumor arising from the ovary’s hormone-making tissue.³¹ They typically make too much estrogen, AMH, and inhibin.³² A specific change in the FOXL2 gene marks nearly all of these tumors.³³ FOXL2 guides how granulosa cells develop and function, and the change helps pathologists confirm the diagnosis on tissue. It is a feature of the tumor cells, not an inherited trait that family members carry.

Inhibin B is raised in about 90% of these tumors.³⁴ High inhibin suppresses FSH, which can cause irregular or missed periods before menopause.³⁵ Inhibin and AMH blood tests help doctors diagnose these tumors and check for recurrence.³⁶

Excess estrogen thickens the uterine lining, which is why unusual bleeding is a leading sign. Bleeding after menopause can reflect tumor estrogen, and younger women may notice heavy or irregular periods. A pelvic mass found on exam or scan also prompts testing. In girls before puberty, excess estrogen can cause early breast development, though that is much rarer.

Stress, Chemicals, and Follicle Loss

Most follicles never ovulate and instead break down, and granulosa cell death is the hallmark of that process.³⁷ Oxidative stress damages granulosa cells’ energy supply and their support of the egg.³⁸ Immune cells in the theca layer release growth factors that help granulosa cells survive.³⁹

Plastics chemicals add another concern. In rat ovary cells, BPA raised testosterone in theca cells.⁴⁰ It also lowered estradiol and the converting enzyme in granulosa cells.⁴¹ In cow cells, the substitute BPS left theca cells alone and appeared to target the estrogen step.⁴² These lab findings suggest some plastics chemicals hit the granulosa step, though effects in women are not established.

For people who want to cut BPA exposure anyway, a few habits help: avoid heating food in polycarbonate plastic containers, choose glass or stainless steel for hot liquids, and limit canned foods with plastic linings. “BPA-free” products may use related chemicals.