hPL

**Origin and structure** - Produced by the syncytiotrophoblast of the placenta. - It is structurally similar to growth hormone (GH) and prolactin. The genes are on chromosome 17, in the same family as GH. - It is detectable by about week 3-4 of gestation. Levels rise steadily and peak near term (about 34-36 weeks), in proportion to placental mass. - It has a short half-life (about 15-30 minutes) and is secreted mainly into maternal blood.

**Physiologic actions (maternal)** - Acts as an anti-insulin, diabetogenic hormone. It decreases maternal insulin sensitivity and glucose uptake, so more glucose and amino acids reach the fetus. - Increases lipolysis, which raises maternal free fatty acids and ketones. These serve as the maternal fuel source. - Has weak GH-like (anabolic) effects, which promote fetal growth through increased IGF production. - Has weak prolactin-like effects that help prepare the breast for lactation. This is a minor effect, and the main driver is prolactin.

**Clinical significance** - **Gestational diabetes mellitus (GDM):** hPL, together with placental cortisol, progesterone, estrogen, and placental GH variant (hPGH), drives the insulin resistance of the second and third trimesters. GDM is typically screened for at 24-28 weeks. After delivery, the insulin resistance resolves quickly once the placenta is expelled. Insulin requirements fall dramatically postpartum. - **Fetal macrosomia:** maternal hyperglycemia leads to fetal hyperinsulinemia and macrosomia. - **Placental function:** hPL levels reflect placental mass. Low levels were historically used to assess placental insufficiency, but this is no longer common practice. Levels may be elevated with multiple gestations or a large placenta and low with placental insufficiency, molar pregnancy, or choriocarcinoma (variable). - **Fasting physiology in pregnancy:** pregnancy is a state of "accelerated starvation." Mothers develop ketosis faster during fasting, partly through hPL-mediated lipolysis.

**High-yield comparison** - hCG: maintains the corpus luteum in early pregnancy (peaks around 8-10 weeks). It shares an alpha subunit with LH, FSH, and TSH. - hPL: rises with placental mass and causes maternal insulin resistance. - Progesterone: maintains the endometrium and uterine quiescence. - Estrogen (estriol): reflects fetal-placental well-being. Estriol is low in Down syndrome on the quad screen.

**Mnemonic:** hPL = "Placental Lactogen = Pregnancy's Little diabetogen" (it makes mom insulin-resistant to feed the fetus).