luteinizing hormone

STRUCTURE/SYNTHESIS: LH is a glycoprotein heterodimer with an α subunit shared with FSH, TSH, and hCG, and a unique β subunit conferring specificity. It is secreted by basophilic gonadotrophs of the anterior pituitary. Pulsatile hypothalamic GnRH stimulates LH/FSH release (high-frequency pulses favor LH; low-frequency pulses favor FSH). Continuous (non-pulsatile) GnRH, e.g., leuprolide, suppresses LH/FSH by receptor downregulation, which is useful in prostate cancer, endometriosis, fibroids, central precocious puberty, and fertility protocols.

MECHANISM: The LH receptor (LHCGR, shared with hCG) is a Gs-coupled GPCR that raises cAMP and activates PKA.

FEMALE PHYSIOLOGY: - Theca cells: LH stimulates cholesterol → androstenedione (via desmolase, the rate-limiting step, P450scc). Androgens diffuse to granulosa cells. - Granulosa cells: FSH induces aromatase, converting androgens to estrogen. This is the "two-cell, two-gonadotropin" model. - Mid-cycle LH surge (about 24–36 h before ovulation) is triggered by sustained high estradiol, a positive feedback effect. It causes ovulation, completes meiosis I in the oocyte, and luteinizes the follicle. - Luteal phase: LH maintains the corpus luteum, which secretes progesterone. If pregnancy occurs, hCG (an LH analog) rescues the corpus luteum. Otherwise the corpus luteum regresses into the corpus albicans. - Ovulation predictor kits detect the urinary LH surge.

MALE PHYSIOLOGY: - LH acts on Leydig cells to produce testosterone. Testosterone, with FSH acting on Sertoli cells (androgen-binding protein), supports spermatogenesis. - Testosterone provides negative feedback on LH and GnRH. Sertoli cell inhibin B inhibits FSH.

FEEDBACK: - Estrogen and progesterone (and testosterone in males) exert negative feedback on LH, except for the mid-cycle estrogen positive feedback.

CLINICAL CORRELATES (high-yield): - PCOS: elevated LH:FSH ratio (often >2:1), hyperandrogenism, anovulation, and insulin resistance. Tx: weight loss, OCPs, spironolactone, metformin, clomiphene or letrozole for fertility. - Primary hypogonadism (Klinefelter, Turner, primary ovarian insufficiency/menopause, gonadal damage): low sex steroids with high LH and FSH (hypergonadotropic). - Secondary/central hypogonadism (Kallmann syndrome, hyperprolactinemia, pituitary tumor, hypopituitarism, anorexia/athletic amenorrhea): low LH/FSH and low sex steroids. Kallmann syndrome is a failure of GnRH neuron migration with anosmia. - Central precocious puberty: early pulsatile GnRH leads to elevated LH. Tx: GnRH agonist. Peripheral precocious puberty has low LH. - Menopause: ↑ FSH (more than LH) and ↑ LH due to loss of estrogen and inhibin. - Exogenous anabolic steroids: suppress LH/FSH, causing testicular atrophy and infertility. - Testotoxicosis (LHCGR activating mutation): peripheral precocious puberty in boys. - hCG (LH analog) is used to induce ovulation and to treat cryptorchidism. It is elevated in pregnancy, molar pregnancy, and germ cell tumors. - Pharmacology: clomiphene (SERM) blocks hypothalamic estrogen receptors, raising GnRH, LH, and FSH, which induces ovulation. GnRH antagonists (degarelix, elagolix) rapidly reduce LH. - Congenital adrenal hyperplasia can cause elevated androgens that suppress LH/FSH.

MNEMONIC: "LH → Leydig/theca → androgens (LH makes androgens); FSH → Follicle/Sertoli."