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The fetal endocrine system
Last reviewed: 04.07.2025
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[ Fetal hypothalamus
The formation of most hypothalamic hormones begins in the intrauterine period, so all hypothalamic nuclei differentiate by 14 weeks of pregnancy. By the 100th day of pregnancy, the formation of the portal system of the pituitary gland is completed, and the hypothalamic-pituitary system completely completes morphological development by the 19-21st week of pregnancy. Three types of hypothalamic neurohumoral substances have been identified: aminergic neurotransmitters - dopamine, norepinephrine, serotonin; peptides, releasing and inhibiting factors synthesized in the hypothalamus and entering the pituitary gland through the portal system.
Gonadotropin-releasing hormone is produced in utero, but the response to it increases after birth. GnRH is also produced by the placenta. Along with GnRH, significant levels of thyrotropin-releasing hormone (TRH) were found in the fetal hypothalamus at early stages of development. The presence of TRH in the hypothalamus in the first and second trimesters of pregnancy indicates its possible role in regulating TSH and prolactin secretion during this period. The same researchers found immunoreactive somatostatin (growth hormone release inhibitory factor) in 10-22 week-old human fetuses, with its concentration increasing as the fetus grew.
Corticotropin-releasing hormone is a stress hormone thought to play a role in the onset of labor, but whether it is a fetal or placental hormone has yet to be determined.
Fetal pituitary gland
ACTH in the fetal pituitary gland is detected as early as the 10th week of development. ACTH in the umbilical cord blood is of fetal origin. The production of ACTH by the fetus is under the control of the hypothalamus and ACTH does not penetrate the placenta.
Synthesis of ACTH-related peptides in the placenta has been noted: chorionic corticotropin, beta-endorphin, melanocyte-stimulating hormone. The content of ACTH-related peptides increases as the fetus develops. It is assumed that at certain periods of life they perform a trophic role in relation to the fetal adrenal glands.
A study of the dynamics of LH and FSH levels showed that the highest level of both hormones in the fetus occurs in mid-pregnancy (20-29 weeks), with a decrease in their levels by the end of pregnancy. The peak of FSH and LH is higher in the female fetus. According to these authors, as pregnancy progresses in the male fetus, the regulation of hormonal production of the testicles shifts from hCG to LH.
Fetal adrenal glands
By mid-pregnancy, the adrenal glands of the human fetus reach the size of a fetal kidney due to the development of the fetal internal zone, which makes up 85% of the entire gland, and are associated with the metabolism of sex steroids (after birth, this part undergoes atresia at about one year of the child's life). The remaining part of the adrenal gland makes up the definitive ("adult") zone and is associated with the production of cortisol. The concentration of cortisol in the blood of the fetus and amniotic fluid increases in the last weeks of pregnancy. ACTH stimulates the production of cortisol. Cortisol plays an extremely important role - it induces the formation and development of various enzyme systems of the fetal liver, including glycogenogenesis enzymes, tyrosine and aspartate aminotransferase, etc. The enzyme induces the maturation of the epithelium of the small intestine and the activity of alkaline phosphatase; participates in the transfer of the body from the fetal to the adult type of hemoglobin; induces differentiation of alveolar cells of type II and stimulates synthesis of surfactant and its release into the alveoli. Activation of the adrenal cortex apparently takes part in the initiation of labor. Thus, according to research data, under the influence of cortisol, secretion of steroids changes, cortisol activates enzymatic systems of the placenta, providing secretion of unconjugated estrogens, which are the main stimulator of release of nr-F2a, and therefore labor. Cortisol affects the synthesis of adrenaline and noradrenaline by the adrenal medulla. Cells producing catecholamines are determined already in the 7th week of pregnancy.
Fetal gonads
Although the fetal gonads originate from the same rudiment as the adrenal glands, their role is quite different. The fetal testes are already visible by the 6th week of pregnancy. The interstitial cells of the testes produce testosterone, which plays a key role in the development of the boy's sexual characteristics. The time of maximum testosterone production coincides with the maximum secretion of chorionic gonadotropin, which indicates the key role of chorionic gonadotropin in the regulation of fetal steroidogenesis in the first half of pregnancy.
Much less is known about the fetal ovaries and their function; they are morphologically detected at 7-8 weeks of development, and cells with features indicating their ability to steroidogenesis have been identified in them. The fetal ovaries begin active steroidogenesis only at the end of pregnancy. Apparently, due to the large production of steroids by the placenta and the mother-fetus organism, the female does not need its own steroidogenesis in the ovaries for sex differentiation.
Thyroid and parathyroid glands of the fetus
The thyroid gland shows activity already at the 8th week of pregnancy. The thyroid gland acquires characteristic morphological features and the ability to accumulate yogin and synthesize iodothyronines by the 10-12th weeks of pregnancy. By this time, thyrotrophs are detected in the pituitary gland of the fetus, TG in the pituitary gland and in the serum, and T4 in the serum. The main function of the thyroid gland of the fetus is participation in tissue differentiation, primarily nervous, cardiovascular, and musculoskeletal. Until the middle of pregnancy, the function of the thyroid gland of the fetus remains at a low level, and then after 20 weeks it is significantly activated. It is believed that this is the result of the process of fusion of the portal system of the hypothalamus with the portal system of the pituitary gland and an increase in the concentration of TSH. The concentration of TSH reaches its maximum by the beginning of the third trimester of pregnancy and does not increase until the end of pregnancy. The content of T4 and free T4 in the serum of the fetus progressively increases during the last trimester of pregnancy. T3 is not detected in the fetus's blood until 30 weeks, then its content increases towards the end of pregnancy. The increase in T3 at the end of pregnancy is associated with an increase in cortisol. Immediately after birth, the T3 level increases significantly, exceeding the intrauterine level by 5-6 times. The TSH level increases after birth, reaching a maximum after 30 minutes, then gradually decreases on the 2nd day of life. The level of T4 and free T4 also increases towards the end of the first day of life and decreases gradually towards the end of the first week of life.
It is suggested that thyroid hormones increase the concentration of nerve growth factor in the brain and, in this regard, the modulating effect of thyroid hormones is realized in the process of brain maturation. With a lack of iodine and insufficient production of thyroid hormones, cretinism develops.
The parathyroid glands actively regulate calcium metabolism at birth. There is a compensatory reciprocal functional relationship between the parathyroid glands of the fetus and mother.
Thymus gland
The thymus is one of the most important glands of the fetus, appears at 6-7 weeks of embryonic life. At 8 weeks of pregnancy, lymphoid cells - prothymocytes - migrate from the yolk sac and liver of the fetus, and then from the bone marrow, and colonize the thymus. This process is not yet precisely known, but it is assumed that these precursors can express certain surface markers that selectively bind to the corresponding cells of the thymus vessels. Once in the thymus, prothymocytes interact with the thymus stroma, resulting in intensive proliferation, differentiation and expression of T-cell-specific surface molecules (CD4+ CD8). Differentiation of the thymus into two zones - cortical and cerebral - occurs at 12 weeks of pregnancy.
In the thymus, complex differentiation and selection of cells occurs in accordance with the major histocompatibility complex (MHC), as if a selection of cells that meet this complex is carried out. Of all the incoming and proliferating cells, 95% will undergo apoptosis 3-4 days after their last division. Only 5% of the cells that undergo further differentiation survive, and cells carrying certain CD4 or CD8 markers enter the bloodstream at 14 weeks of pregnancy. Thymus hormones are involved in the differentiation of T-lymphocytes. The processes occurring in the thymus, migration and differentiation of cells became more understandable after the discovery of the role of cytokines, chemokines, expression of genes responsible for this process and, in particular, the development of receptors that perceive all kinds of antigens. The process of differentiation of the entire repertoire of receptors is completed by the 20th week of pregnancy at the level of an adult.
In contrast to alpha-beta T4 cells expressing CD4 and CD8 markers, gamma-beta T lymphocytes express CD3. At 16 weeks of pregnancy, they constitute 10% of the peripheral blood, but they are found in large quantities in the skin and mucous membranes. In their action, they are similar to cytotoxic cells in adults and secrete IFN-γ and TNF.
The cytokine response of fetal immunocompetent cells is lower than that of an adult, so il-3, il-4, il-5, il-10, IFN-y are lower or practically undetectable when stimulating lymphocytes, and il-1, il-6, TNF, IFN-a, IFN-β, il-2 - the response of fetal cells to mitogens is the same as that of an adult.