Endocrine changes in pregnancy
The placenta
There are significant changes in all maternal endocrine organs in pregnancy. These changes are dominated by the considerable production of sex steroids produced by the placenta.
Human chorionic gonadotropin is the signal for pregnancy that stimulates physiological changes. High levels of oestrogen stimulate increased hepatic synthesis of binding globulins such as thyroid-binding globulin, which is doubled by the end of the first trimester, and cortisol- binding globulin, which is doubled by the end of pregnancy; these also impact the mother's wider endocrinological function.Large amounts of oestrogen and progesterone are produced by the fetoplacental unit. These are important for uterine growth and quiescence. Oestrogens stimulate the synthesis of vascular endothelial growth factor and angiogenesis. This in turn interacts with angiopoietin-2 and other placentally derived hormones which are vital in the formation of the villous capillary bed in early pregnancy. The human villous and extravillous cytotrophoblasts express the peroxisome proliferator-activated receptor gamma. This is a nuclear receptor that binds eicosanoids, fatty acids, and oxidized low-density lipoproteins which is essential for placental development (67).
The hypothalamus and pituitary
The pituitary gland increases in weight by 30% in nulliparous women and by 50% in multiparous women. This increase is largely due to changes in the anterior pituitary. The anterior pituitary produces three glycoproteins: luteinizing hormone (LH), follicular-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). It also produces three polypeptide and peptide hormones: growth hormone (GH), prolactin, and adrenocorticotropic hormone (ACTH). The elevated oestrogen levels in pregnancy cause an increase in the number of lactotrophs. Within a few days of conception, plasma prolactin concentrations begin to increase and this continues steadily until a surge at the time of delivery and subsequent decrease.
By term, prolactin concentrations are increased 10-20 times compared to non-pregnancy (68). They remain raised above basal levels while breastfeeding. All other anterior pituitary hormones are either relatively constant or reduced. The high concentration of human chorionic gonadotropin suppresses secretion of FSH and LH thus inhibiting ovarian follicle development. TSH remains constant. ACTH concentrations rise but remain within the normal non-pregnant range. This rise is due to placental synthesis of ACTH and corticotropin-releasing hormone (CRH) which is normally produced in the hypothalamus. Therefore, ACTH does not respond to normal control mechanisms in pregnancy. Plasma levels of CRH increase in the third trimester and are thought to be a potential trigger for labour.The posterior pituitary releases AVP and oxytocin. Renal clearance of AVP is increased (see ‘Changes in the renal system'). Oxytocin concentrations are low during pregnancy and their effects on uterine contractility were described earlier in ‘Changes in uterine physiology'.
The thyroid and parathyroids
The thyroid gland enlarges in up to 70% of pregnant women; this varies according to iodine intake. Iodine uptake by the thyroid is increased threefold, urine excretion increases, and iodothyronines are transferred to the fetus, thus plasma inorganic iodide levels in the mother decrease (69). Concentrations of thyroid-binding globulin double in pregnancy (70). Concentrations of total tri-iodothyronine (T3) and thyroxine (T4) are increased in very early pregnancy then decrease to the non-pregnant range. T3, T4, and TSH do not cross the placental barrier and therefore have no direct effect on fetal thyroid function.
Calcitonin, also produced in the thyroid, increases during the first trimester, peaks in the second, and then decreases. It may contribute to the regulation of 1,25-dihydroxyvitamin D. Parathyroid hormone (PTH), produced by the parathyroids, regulates synthesis of 1,25-dihydroxyvitamin D in the proximal convoluted tubule.
During pregnancy, the placenta and the fetal parathyroid gland produce PTH-related protein which also affects calcium homeostasis by acting on PTH receptors.Renal hormones
The RAS is activated from very early pregnancy as explored earlier in the cardiovascular section. Angiotensin II acts through directly opposing receptors. ATi receptors promote angiogenesis hypertrophy and vasoconstriction. AT2 receptors promote apoptosis. It is thought that AT2 expression dominates in early pregnancy implantation and vascular remodelling (71).
Adrenal hormones
In pregnancy, the rise in ACTH stimulates cortisol synthesis and there is a rise in total plasma cortisol concentrations from the end of the first trimester. Concentrations of cortisol-binding globulin double but despite this, the concentration of free cortisol also increases during pregnancy and the diurnal variation is lost (72). Excess glucocorticoid exposure to the growing fetus inhibits fetal growth. However, the normal placenta synthesizes 11β-hydroxysteroid dehydrogenase which inhibits the transfer of maternal cortisol to the fetus. High circulating oestrogen increases the production of sex hormone-binding globulin which in turn results in an increase in total testosterone levels (73). Plasma catecholamine concentrations decrease from the first to the third trimester.
Clinical considerations
• Most women are euthyroid in pregnancy.
• Grave's hyperthyroidism is often improved in pregnancy with a reduction in the antibody titre. Maternal thyroid disease usually does not directly affect the fetus. However, if this does not occur, antibodies will cross the placenta, stimulating the fetal thyroid. This can be evidenced by signs of fetal hyperthyroidism such as tachycardia, intrauterine growth restriction, and cardiac failure. In addition, iodine is required for fetal thyroid growth and antithyroid drugs do cross the placenta. The fetus can also be affected by the implications of autoimmune thyroid disease.
• Labour is associated with massive increases in adrenaline and noradrenaline as a result of stress and muscle activity.
More on the topic Endocrine changes in pregnancy:
- Chapter 9 Obstetric conditions
- Agrawal M.. Textbook of Pediatrics. 3rd ed. — CBS Publishers,2025. — 973 p., 2025