theca cell

**Location and types:** Theca cells form the outer layers of the developing ovarian follicle, separated from granulosa cells by the basement membrane. Theca interna is the vascularized, steroidogenic inner layer. Theca externa is the fibrous, connective-tissue outer layer.

**Two-cell, two-gonadotropin model of estrogen synthesis:** - Theca cells have LH receptors. LH stimulates cholesterol → pregnenolone (via desmolase, the rate-limiting step, also called P450scc or CYP11A1) → androstenedione and testosterone. - Androgens diffuse across the basement membrane into granulosa cells. Theca cells have no aromatase, so they cannot make estrogen. - Granulosa cells have FSH receptors. FSH induces aromatase (CYP19A1), which converts androstenedione → estrone and testosterone → estradiol. Estradiol is the main product. - Memory aid: "LH acts on theca (androgens); FSH acts on granulosa (aromatase)." Theca = LH, Granulosa = FSH.

**After ovulation:** The follicle becomes the corpus luteum. Theca-lutein cells (from theca interna) and granulosa-lutein cells (from granulosa) secrete progesterone, and also estrogen and inhibin A. This is supported by hCG in early pregnancy.

**Clinical correlations:** - **PCOS:** Increased LH:FSH ratio (often >2:1) causes theca cell hyperplasia and excess androgen production. Hyperinsulinemia and insulin resistance also stimulate theca cell androgen output. Features: oligo/anovulation, hirsutism, acne, and polycystic ovaries (Rotterdam criteria: 2 of 3). Treatment includes OCPs, weight loss, metformin, spironolactone, and clomiphene or letrozole for fertility. - **Ovarian thecoma / granulosa-theca cell tumors (sex cord-stromal tumors):** Produce estrogen and can cause precocious puberty, endometrial hyperplasia or carcinoma, or postmenopausal bleeding. Granulosa cell tumors have Call-Exner bodies (small follicle-like structures with eosinophilic material) and are inhibin-positive. Thecomas are composed of lipid-laden spindle cells. Fibromas, if associated with ascites and pleural effusion, are Meigs syndrome. - **Theca-lutein cysts:** Caused by high hCG (hydatidiform mole, choriocarcinoma) or ovarian hyperstimulation syndrome. They are often bilateral and multiple. - **Aromatase deficiency or inhibitors:** Androgens accumulate and estrogen is low. Aromatase inhibitors (anastrozole, letrozole) are used in ER+ breast cancer. - **17α-hydroxylase deficiency:** Reduced sex-steroid synthesis in theca cells (and the adrenals and gonads) leads to low androgens and estrogens, with hypertension and hypokalemia from excess mineralocorticoid.

**Male analog:** Leydig cells (LH-stimulated, make testosterone) correspond to theca cells, and Sertoli cells (FSH-stimulated, aromatase, inhibin B, ABP) correspond to granulosa cells.