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Endocrine disorders in pregnancy: Physiological and hormonal aspects of pregnancy

https://doi.org/10.1016/j.beem.2011.07.004Get rights and content

The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones during gestation. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, and for parturition. As pregnancy advances, the relative number of trophoblasts increase and the foeto-maternal exchange begins to be dominated by secretory function of the placenta. As gestation progresses toward term, the number of cytotrophoblasts again declines and the remaining syncytial layer becomes thin and barely visible. This arrangement facilitates transport of compounds including hormones and their precursors across the foeto-maternal interface. The endocrine system is the earliest system developing in foetal life, and it is functional from early intrauterine existence through old age. Regulation of the foetal endocrine system relies, to some extent, on precursors secreted by placenta and/or mother.

Highlights

► More research focussing on the physiological endocrine changes during pregnancy in order to be able to diagnose endocrine diseases in pregnant women is warranted. ► Search for better methods for measuring endocrine functions during pregnancy. ► Better research collaboration between endocrinologists and specialist in clinical biochemistry warranted in order to accomplish above 2 important purposes.

Introduction

The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, as well as for parturition. Gestational adaptations during pregnancy include implantation and maintenance of early pregnancy, modification of the maternal system for adequate nutritional support to the developing foetus; and finally, preparation for parturition and subsequent lactation.

As pregnancy advances, the relative number of trophoblasts increase and the foeto-maternal exchange begins to be dominated by the secretory function of the placenta. Later, throughout the second and third trimester, the structure of the placenta further adapts to reflect its function such that near term, the villi consist mainly of foetal capillaries with sparse supporting stroma. In contrast to the early placental villus where trophoblasts are abundant as part of a continuous layer of basal cytotrophoblasts, the term placenta’s membranous interface between the foetal and maternal circulation is extremely thin.1 Thus, as the gestation progresses toward term, the number of cytotrophoblasts declines and the remaining syncytial layer becomes thin and barely visible. This structural arrangement facilitates transport of compounds including hormones and their precursors across the foeto-maternal interface.

The endocrine system is the earliest system developing in foetal life, and it is functional from early intrauterine existence through old age. Regulation of the foetal endocrine system relies, to some extent, on precursors secreted by either placenta or the mother. As the foetus develops, its own endocrine system matures and eventually becomes more independent as preparation for the foetus to cope with extrauterine life.

Section snippets

Early pregnancy-related hormonal activity

Pregnancy-related proteins can be found in the maternal circulation shortly after conception, and chorionic gonadotropin (hCG) is detectable in maternal serum after initiation of implantation. Thus, during the process of implantation the embryo is actively secreting hCG, which can be detected in maternal serum from the 8th day after ovulation. A unique role of hCG is to prolong the hormonal activity of the corpus luteum to continue production of progesterone and maintain the gestational

Hormonal role of the placenta

The placenta plays a pivotal role in balancing foetal growth and development with maternal homeostasis. The foetus develops in an environment where respiration, alimentation and excretory functions are provided by the placenta, which efficiently transfers substances to the foetus, while simultaneously serving as a barrier between the foetus and the mother. The placenta functions partly as a hypothalamic-pituitary-end organ-like entity with stimulatory and inhibitory feedback mechanisms, to

Hypothalamus and pituitary

The foetal hypothalamus develops during the first few weeks of foetal life, and its development is well advanced by 12 weeks. Most of the hypothalamic-releasing hormones, as well as dopamine, norepinephrine, and somatostatin, can be identified by 6–8 weeks of gestation. The anterior pituitary develops from Rathke’s pouch and from week 7 it is capable of secreting growth hormone (GH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and adrenocorticotropic hormone (ACTH). However,

The thyroid gland

The function of the thyroid gland is to generate the quantity of thyroid hormone necessary to meet the demands of the peripheral tissues. Overall, the thyroid and the thyroid hormones, tri-iodo-thyronine (T3) and thyroxine (T4), participate with the hypothalamus, secreting thyrotropin releasing hormone (TRH), and pituitary, secreting thyrotropin (TSH) in a classical feedback controlled loop. All processes in thyroid are initiated by binding of TSH to the TSH-receptor. In the circulation the

Adrenal glands

The foetal adrenal gland has a unique morphology and capacity for intrauterine steroid biosynthesis. The foetal adrenals are disproportionately large, and at mid-pregnancy they are larger than the foetal kidneys. At term, the adrenals are as large as those of adults, weighing 10 g or more. The unique inner foetal zone comprises 80–85% of the volume of the foetal adrenal, and is largely responsible for the tremendous growth and secretory capacity of this organ. The foetal zone rapidly undergoes

Insulin and metabolic homeostasis

In early pregnancy glucose tolerance is generally normal and peripheral sensitivity to insulin and glucose similar to pre-gravid levels.53 The insulin response to an oral glucose is enhanced with an increase in the first phase insulin response. Insulin sensitivity may vary depending on a women’s pre-pregnancy metabolic status. For example, insulin sensitivity may increase if the women is very insulin resistant or may decrease if extremely insulin sensitive.53 Over the course of gestation the

Parathyroid glands and calcium homeostasis

The amount of calcium to the foetus is regulated by transfer of calcium across the placenta from the mother. Maternal compartment changes permit calcium accumulation by increases in maternal dietary intake and doubling of intestinal calcium absorption by 12th week of pregnancy, increases in maternal 1,25-dihydroxyvitamin D3 levels, and increases in parathyroid hormone levels, thus maintaining foetal bone growth. A placental calcium pump creates a gradient of calcium and phosphorus that favours

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