Fetal endocrine system
Last reviewed: 11.04.2020
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Hypothalamus of the fetus
The formation of most hypothalamic hormones begins in the prenatal period, so all the hypothalamic nuclei differentiate to 14 weeks of pregnancy. By the 100th day of pregnancy, the portal system of the pituitary gland is being completed, and the hypothalamic-pituitary system completes the morphological development by the 19-21 week of pregnancy. Three types of hypothalamic neurohumoral substances were identified: aminergic neurotransmitters-dopamine, norepinephrine, serotonin; peptides, releasing and inhibiting factors synthesized in the hypothalamus and entering the pituitary gland through the portal system.
Gonadotrophic releasing hormone is produced in utero, but the degree of response to it increases after birth. GnRH is produced by the placenta. Along with GnRH, a significant amount of thyrotropin-releasing hormone (TRH) in the hypothalamus of the fetus was detected in the early stages of its development. The presence of TRH in the hypothalamus in the I and II trimesters of pregnancy indicates its possible role in the regulation of secretion of TSH and prolactin during this period. The same investigators detected immunoreactive somatostatin (a factor that inhibited the release of growth hormone) in the 10-22 week old human fetus, and its concentration increased as the fetus grew.
Corticotropin-releasing hormone, a stress hormone, is believed to play a role in the development of labor, but this fetal or placental hormone has yet to be determined.
Fetal pituitary gland
ACTH in the pituitary gland is determined at the 10th week of development. ACTH in the blood of the umbilical cord has fetal origin. The production of the fetal ACTH is under the control of the hypothalamus and ACTH does not penetrate the placenta.
Synthesis of related ACTH peptides in the placenta was noted: chorionic corticotropin, beta-endorphin, melanocyte-stimulating hormone. The content of related ACTH peptides increases as the fetus develops. It is assumed that at certain periods of life they perform a trophic role in relation to the adrenal glands of the fetus.
A study of the dynamics of the content of LH and FSH showed that the highest level of both hormones in the fetus occurs in the middle of pregnancy (20-29 weeks), with a decrease in their levels by the end of pregnancy. The peak of FSH and LH is higher in females. According to these authors, as pregnancy increases in the male fetus, the regulation of the hormonal production of the testes changes from HG to LH.
The adrenal glands of the fetus
The adrenal glands of the fetus reach the size of the fetal kidney by the middle of pregnancy, due to the development of the fetal inner zone, which is up to 85% of the entire gland, and is associated with the metabolism of sex steroids (after birth this part undergoes atresia about a year of the child's life). The rest of the adrenal gland forms 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 exceptionally important role - it induces the formation and development of various enzyme systems of the fetal liver, including enzymes of glycogenogenesis, tyrosine and aspartate aminotransferase, etc. The enzyme induces maturation of the epithelium of the small intestine and the activity of alkaline phosphatase; participates in the transfer of the body from fetal to adult type of hemoglobin; induces differentiation of alveolar cells of type II and stimulates the synthesis of surfactant and its release into alveoli. Activation of the adrenal cortex, apparently, takes part in the unleashing of labor. So, according to research, under the influence of cortisol, the secretion of steroids changes, cortisol activates the enzyme systems of the placenta, securing the secretion of unconjugated estrogens, which are the main stimulant for the release of nr-F2a, and hence birth. Cortisol affects the synthesis of epinephrine and the norepinephrine layer of the adrenal gland. Cells that produce catecholamines are determined as early as 7 weeks of gestation.
Fetal gonads
Although the gonads of the fetus originate from the same rudiment, that, the adrenal glands, their role is quite different. Fetal testicles are detected already by the 6th week of pregnancy. Interstitial testicular cells produce testosterone, which plays a key role in the development of the boy's sexual characteristics. The time of maximum production of testosterone coincides with the maximum secretion of chorionic gonadotropin, which indicates the key role of chorionic gonadotropin in regulating fetal steroidogenesis in the first half of pregnancy.
Much less is known about the ovaries of the fetus and their functions, morphologically they are detected on the 7-8th week of development, and cells with signs indicative of their ability to steroidogenesis are revealed in them. Active fetal ovaries start only at the end of pregnancy. Apparently, due to the large production of steroids by the placenta and the body, the female mother in the sex differentiation does not need its own steroidogenesis in the ovaries.
[15], [16], [17], [18], [19], [20], [21]
Thyroid and parathyroid glands of the fetus
The thyroid gland shows activity already on 8 week of pregnancy. Characteristic morphological features and the ability to accumulate yoga and synthesize iodothyronine thyroid gland will acquire by 10-12 weeks of pregnancy. By this time, thyrotrophs are detected in the pituitary gland, TG in the pituitary gland and in serum and in serum T4. The main function of the thyroid of the fetus is to participate in the differentiation of tissues, primarily the nervous, cardiovascular and locomotor. Until the middle of pregnancy, the thyroid function of the fetus remains at a low level, and then after 20 weeks is significantly activated. It is believed that this is the result of the process of the fusion of the portal system of the hypothalamus with the portal system of the pituitary gland and with the increase in the concentration of TSH. Its maximum concentration of TSH reaches 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 fetal serum progressively increases during the last trimester of pregnancy. TK is not detected in fetal blood until 30 weeks, then its content increases by the end of pregnancy. The increase in TK at the end of pregnancy is associated with an increase in cortisol. Immediately after birth, the level of TK significantly increases, exceeding the intrauterine 5-6 times. The level of TSH 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 by the end of the first day of life and decreases gradually by the end of the first week of life.
There is an assumption that thyroid hormones increase the concentration of nerve growth factor in the brain and, in this connection, the modulating effect of thyroid hormones is realized during the maturation of the brain. With a shortage of iodine and inadequate production of thyroid hormones, cretinism develops.
At the time of birth, the parathyroid glands actively regulate calcium metabolism. Between the parathyroid glands of the fetus and the mother there is a compensatory reciprocal functional connection.
Thymus
Thymus is one of the most important fetal glands, appears on the 6-7th week of embryonic life. At the 8th week of pregnancy, lymphoid cells - protimotsity - migrate from the yolk sac and fetal liver, and then from the bone marrow, and colonize the thymus. This process is not yet known precisely, but it is suggested that these precursors can express certain surface markers that selectively bind to the corresponding cells of the thymus vessels. Once in the thymus, the protymocytes act with the thymic 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 there is a complex differentiation and selection of cells in accordance with the main complex of histocompatibility (MHC), as if the cells that correspond to this complex are selected. Of all the incoming and proliferating cells, 95% will undergo apoptosis 3-4 days after their last division. Only 5% of the cells survive, which are further differentiated, and cells carrying certain markers of CD4 or CD8 enter the bloodstream at 14 weeks of gestation. Thymus hormones are involved in the differentiation of T-lymphocytes. The processes occurring in the thymus, migration and cell differentiation became more understandable after the discovery of the role of cytokines, chemokines, the 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 adult level.
Unlike alpha-beta-T4 in cells expressing the markers CD4 and CD8, gamma-beta T-lymphocytes express CD3. At 16 weeks of pregnancy, they are 10% in peripheral blood, but they are found in large quantities in the skin and in mucous membranes. By their action they are similar to cytotoxic cells in adults and secrete IFN-y and TNF.
The cytokine response of fruit 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, a il-1, il-6, TNF , IFN-a, IFN-R, il-2-response of fetal cells to mitogens is the same as in an adult.