LH

**Structure:** LH is a glycoprotein hormone with an α subunit shared with FSH, TSH, and hCG, and a hormone-specific β subunit. hCG is structurally and functionally similar to LH and acts on the same receptor.

**Regulation:** - Hypothalamic GnRH is released in a pulsatile manner and stimulates LH and FSH release. Continuous (non-pulsatile) GnRH, such as from leuprolide, instead downregulates the receptors and suppresses LH and FSH. This is the basis for using GnRH agonists in prostate cancer, endometriosis, fibroids, and central precocious puberty. - Females: Low-level estrogen exerts negative feedback on LH. Sustained high estrogen at mid-cycle switches to positive feedback and causes the LH surge. Progesterone provides negative feedback during the luteal phase. - Males: Testosterone gives negative feedback on LH and GnRH. Inhibin B selectively inhibits FSH.

**Actions (receptor: Gs-coupled GPCR, so cAMP/PKA):** - Females: LH acts on theca cells to make androgens from cholesterol. Granulosa cells (under FSH) convert those androgens to estrogen via aromatase. The mid-cycle LH surge causes ovulation (about 10–12 hours later), completes meiosis I in the oocyte, and luteinizes the follicle into the corpus luteum, which secretes progesterone. - Males: LH acts on Leydig cells to make testosterone. FSH acts on Sertoli cells to support spermatogenesis and make inhibin B and androgen-binding protein.

**Clinical correlations:** - PCOS: Increased LH:FSH ratio (often >2:1) with theca-cell androgen excess, anovulation, hirsutism, and polycystic ovaries. Treatment includes OCPs, spironolactone, metformin, and clomiphene or letrozole for ovulation induction. - Primary hypogonadism (testicular or ovarian failure, Turner syndrome, Klinefelter syndrome, menopause): ↓ sex steroids with ↑ LH and ↑ FSH. - Secondary (central) hypogonadism: ↓ LH, ↓ FSH, and ↓ sex steroids. Causes include Kallmann syndrome (anosmia plus GnRH deficiency from failed GnRH neuron migration), hyperprolactinemia, pituitary tumors, and Sheehan syndrome. - Hyperprolactinemia: Inhibits GnRH, which lowers LH and FSH. This causes amenorrhea or infertility in women and ↓ libido or erectile dysfunction in men. - Anabolic steroid use: Suppresses LH, which causes testicular atrophy and low intratesticular testosterone. - hCG: Used to induce ovulation in assisted reproduction because it mimics the LH surge. Home ovulation kits detect the urinary LH surge. - Gonadotroph-secreting precocious puberty: Central (GnRH-dependent) precocious puberty has a high LH response to a GnRH stimulation test. Peripheral causes have a low LH. - Congenital adrenal hyperplasia (e.g., 21-hydroxylase deficiency): Excess androgens suppress LH and FSH, which causes anovulation.

**High-yield pearls:** - LH surge → ovulation → corpus luteum → progesterone (luteal phase, about 14 days fixed). - LH = theca cells (androgens) and Leydig cells (testosterone). Mnemonic: "LH = Leydig, Luteinization, and theca (LTH)." - FSH = Follicle, Sertoli, and aromatase induction in granulosa cells. - Both LH and FSH are decreased by pregnancy (↑ estrogen/progesterone), hyperprolactinemia, and exogenous sex steroids.

**Note:** On exams, "LH" can occasionally refer to other terms, such as left hemisphere or lateral hypothalamus. In endocrine and reproductive contexts it nearly always means luteinizing hormone.