O3. Endocrinology of Pregnancy and Parturition

I. Placenta as Endocrine Organ

General Concept

• Pregnancy endocrine system: placenta + corpus luteum + maternal pituitary/thyroid/adrenal/pancreas + fetus.
• Placenta produces: hCG, progesterone, estrogens, hPL/hCS, placental growth hormone and CRH.
• Main exam logic: early pregnancy depends on corpus luteum; later pregnancy depends mainly on placenta.
• Luteal-placental shift: placenta becomes main progesterone/estrogen source around 9-10 weeks.

II. Main Pregnancy Hormones

hCG

• Source: syncytiotrophoblast.
• Structure: glycoprotein; alpha-subunit shared with LH/FSH/TSH, beta-subunit is specific.
• Secretion: detectable in maternal serum about 7-9 days after fertilization; rises rapidly; peaks around 8-10 weeks; then lower plateau.
• Main function: maintains corpus luteum → progesterone production → maintenance of early pregnancy.
• Other effects: stimulates fetal Leydig cells → testosterone; weak TSH-like activity.
• Very high hCG: transient TSH suppression ± gestational transient thyrotoxicosis.
• Clinical use: pregnancy test, early pregnancy/ectopic follow-up, trophoblastic disease, aneuploidy screening.

Progesterone

• Source: corpus luteum early → placenta later.
• Main function: maintains pregnancy and uterine quiescence.
• Effects: maintains decidua, decreases myometrial contractility, thick cervical mucus, immune tolerance.
• Smooth muscle relaxation: constipation, reflux, ureteric dilatation.
• Parturition concept: humans do not need a major fall in serum progesterone; functional progesterone withdrawal permits labor.

Estrogens

• Main pregnancy estrogen: estriol (E3).
• Source: fetoplacental unit.
• Pathway: fetal adrenal DHEA-S → placenta → estrogens, especially estriol.
• Effects: uterine growth, uterine blood flow, breast ductal growth, hepatic binding proteins.
• Toward term: increases myometrial excitability, oxytocin receptors, gap junctions and prostaglandins.

hPL / hCS

• Human placental lactogen / human chorionic somatomammotropin.
• Source: syncytiotrophoblast.
• Level: rises with gestational age and placental mass.
• Main function: maternal insulin resistance + lipolysis → more glucose available for fetus.
• Clinical consequence: diabetogenic effect in second half of pregnancy → GDM in susceptible women.

III. Maternal Endocrine Adaptations

Prolactin and Oxytocin

• Prolactin source: maternal anterior pituitary.
• Pregnancy: estrogen → lactotroph hyperplasia → prolactin increases → breast preparation.
• During pregnancy: high estrogen/progesterone inhibit abundant milk secretion.
• After placental delivery: estrogen/progesterone fall → prolactin can drive milk synthesis.
• Suckling: increases prolactin → milk production.
• Oxytocin: hypothalamus → posterior pituitary release → uterine contraction + milk ejection.

Thyroid

• Estrogen → increased thyroxine-binding globulin (TBG) → increased total T4/T3.
• Free T4/T3: usually physiologic; use pregnancy-specific reference ranges.
• hCG has TSH-like activity → early pregnancy thyroid stimulation → TSH often decreases in 1st trimester.
• Do not memorize “TSH increases in pregnancy” as the general rule.
• Maternal TSH: does not significantly cross placenta.
• Maternal thyroid hormone crosses partly; TSH-receptor antibodies can cross and affect fetus.

Metabolic and Adrenal Changes

• Early pregnancy: anabolic → maternal fat and glycogen storage.
• Late pregnancy: catabolic/insulin-resistant → maternal lipolysis + fetal glucose supply.
• Main diabetogenic hormones: hPL, placental growth hormone, progesterone, cortisol.
• Cortisol increases due to cortisol-binding globulin and HPA/placental CRH activity.

IV. Endocrinology of Parturition

Transition to Labor

• Labor trigger: multifactorial; no single hormone explains onset.
• Sequence: uterine quiescence → activation → coordinated contractions → delivery.
• Functional progesterone withdrawal → increased contractility and prostaglandin action.
• Increased estrogen effect → oxytocin receptors, gap junctions, prostaglandins.

Prostaglandins

• Main mediators: PGE2 and PGF2-alpha.
• Source: decidua and fetal membranes.
• PGE2: cervical ripening + contractions.
• PGF2-alpha: myometrial contractions.

Fetal HPA Axis and Placental CRH

• Toward term: placental CRH increases.
• Placental CRH + fetal HPA axis → fetal adrenal cortisol and DHEA-S increase.
• Fetal cortisol: maturation + placental CRH/prostaglandin activation.
• Fetal DHEA-S → placental estrogen synthesis → uterine activation.

Oxytocin and Ferguson Reflex

• Ferguson reflex: cervical stretch → oxytocin release → stronger contractions → more cervical stretch.
• After delivery: oxytocin → uterine contraction → reduced postpartum bleeding.

Cervical Ripening

• Cervix changes from firm/closed → soft, effaced and dilatable.
• Mediators: prostaglandins, cytokines, nitric oxide, extracellular matrix remodeling.

V. After Placental Delivery

Hormonal Fall and Lactation

• Placental delivery → rapid fall of hCG, hPL, progesterone and estrogens.
• Estrogen/progesterone fall → prolactin-mediated milk synthesis begins.
• Suckling → prolactin for production + oxytocin for milk ejection.
• Oxytocin → postpartum uterine contraction → hemostasis.