Bertino E

Thyroid hormones in tissues from human embryos and fetuses

This study was intended to quantify T3 and T4 in various human tissues at different stages of gestation as a contribute in the evaluation of the role of thyroid hormones in fetal development, particularly before the maturation of fetal thyroid function. Moreover, for a better comprehension of the influence of thyroid hormone status in tissues, the study was extended to adults. Embryonic specimens were obtained from voluntary abortions between 6 and 12 weeks of gestation, fetal and neonatal specimens from fetuses and neonates between 15 and 36 weeks of gestation after spontaneous abortion or stillbirth, and adult specimens from men (age range: 45–65 years) after death for cardiovascular diseases. Thyroid hormones were measured by the method of Gordon and coworkers. In embryos T3 and T4 were measured in limbs, carcasses, brain and liver: considering all values measured in the period 9–12 weeks, a mean concentration of 0.11 ng/g for T3 and 1.28 ng/g for T4 was obtained. In pooled limbs of 6–8 weeks T3 was barely measurable (0.01 ng/g). In the carcasses there was an increase in T3 and T4 concentrations of 40 and 20 times respectively from the 9th to the 12th week, when thyroid follicles oir-ganization takes place. In fetuses and adults T3 and T4 were measured in brain, heart, kidney, liver, lung, skeletal muscle and skin (mean concentrations: 0.86 ng/g for T3 and 7.44 ng/g for T4 in fetuses and neonates; 1.36 ng/g for T3 and 12.75 ng/g for T4 in adults). Hormones concentration increased with gestational age; the T3/T4 ratio increased until 22–24 weeks, when the prevalent increment in T4 occurs. T3 concentration up to 30 weeks was generally higher in tissues than in cord serum of the corresponding age. During the last month of gestation T3 increment was faster in serum. T4 level was always predominant in serum. In conclusion, T3 and T4 have been detected in the limbs of embryos before the onset of thyroid hormone secretion. Concentrations were 1/150 and 1/70, of the normal maternal blood values respectively. It is conceivable that these hormones are of maternal origin, and the question of whether such small quantities may play a role in fetal development is open.

Immunolike growth hormone substance in tissues from human embryos/fetuses and adults

GH immunolike reactivity was measured by RIA and IRMA tests in the extracts of tissues from human fetuses (8–32 weeks) and adults. For some fetal tissues a comparison was made with the T4 values obtained in a previous study. Both hormones were already measurable in peripheral tissues at 8 weeks of gestation. The increase in GH was faster than for T4 and it reached the zenith at approximately 20 weeks; thereafter, the GH concentration declined until delivery. In contrast, T4 progressively increased until term. Thirteen tissues were studied both in fetuses and in adults: the GH concentration was about 10 times higher in fetal tissues, with the exception of the brain and the pancreas. The brain showed the lowest GH concentration throughout fetal life and adulthood, whereas the highest GH levels were recorded in adults’ pancreas, but they resulted to be artifacts since the RIA values were not confirmed by the IRMA test. In both groups of subjects the highest GH concentrations were found in kidneys, liver and small intestine; the lowest, beyond the brain, in red muscle and cartilage. Thus, the pattern of the quantitative distribution of GH in fetal tissues is the same as in adults, suggesting a functional role of the hormone in the developing human during the prenatal period, in contrast with the concept that high tissue levels of GH are a mere reflection of high GH blood levels. Moreover, in all tissues examined no correlation was found between GH and T4 concentration.

Development of thyroid function between VI-IX month of fetal life in humans

Well-preserved thyroid glands from 28 fetuses 22–34 weeks of gestational age and from 4 term newborns who survived at most 12 days were examined to study thyroid development in late intrauterine life. Total iodine thyroglobulin (Tg), T4, T3 and rT3 were assayed before and after hydrolysis with pronase. In the same maternity unit the cord-serum of 25 healthy term newborns was also assayed and the urine iodine on the day of delivery was tested in 52 newborns and their mothers. Results are expressed as mean values ± SD. The thyroid gland weight ratio to body weight for the preterms was 0.063 ± 0.024; thyroid Tg content 5.9 ± 4.0 mg/g; total thyroid iodine 41.7 ± 35.1 μg/g; Tg iodination 0.72 ± 0.37%; hormone quota of Tg iodine 39.9 ± 12.4. Molar ratios were: T4/Tg 3.3 ± 1.6, T3/Tg 0.25 ± 0.14, rT3/Tg 0.072 ± 0.059. Considerable differences in thyroid iodine content and Tg iodination were observed although the availability of iodine was presumably the same. The high Tg iodination reflects the enhanced uptake of the fetal thyroid. The quantity of iodine involved in hormonogenesis varied greatly among fetuses of the same gestational age, this being in the third term as active as in fully mature thyroids. Hormonogenesis seemed preferentially directed to production of T4 and rT3, which, in the latter case, is higher peripherically. Four preterms with a particularly low level of hormonogenesis were not seen to have deficient levels of thyroid iodine or Tg iodination and the most compromised step was the iodine utilization in the production of hormones. Altogether in the preterms the Tg and thyroid iodine concentrations are about one tenth of the mean values for adults. This might explain the increased risk preterms have of developing transient hypothyroidism, particularly in iodine poor areas or if diseases adversely affect hormonogenesis.

Adrenocorticotropic hormone and catecholamines in maternal, umbilical and neonatal plasma in relation to vaginal delivery

The aim of this study was to evaluate the effect of vaginal delivery on both ACTH and catecholamines (DA, NE, E) secretion in the mother, the fetus (umbilical artery) and the newborn. Blood samples were obtained from 19 normal pregnant women and the corresponding umbilical cords, and from the newborns. Seventeen normal nonpregnant women, matched for age and parity, were also included in the study as “nonpregnant controls”. The results demonstrate that in the mother, plasma catecholamines (CA) concentrations during labor and delivery are elevated above the values reported for normal nonpregnant women and there is a predominant E response. The concentrations of CA in umbilical arteries are very high compared to those in the corresponding mother and they fall rapidly after birth. Unlike that in the mother, the predominant CA response to parturition in the fetus and newborn infant is NE. The extraction rate of DA, NE and E from placenta is approximately 60%. The peripheral plasma levels of ACTH in pregnant women during labor are twice and 10 times as high as those observed in the corresponding umbilical arteries and in nonpregnant women respectively. At delivery they increase further. No significant differences are found between the values measured in the arterial cord blood and those in the venous cord blood and in the newborns. A way of explaining the prevalence of E and the higher ACTH/E ratio found in the mother in comparison with the fetus could be that in the mother the stress response to parturition is regulated mainly by the pituitary-adrenal axis, whereas in the fetus there is a prevalent stimulation of the sympathetic nervous system.

Glucocorticoid receptors immunoreactivity in tissue of human embryos.

The exact period when glucocorticoid receptors (GR) appear in human embryos is unknown, however their presence is acknowledged in target tissues before the fetal adrenal cortex secretes Cortisol. Determining when GR develop could serve as an index of the importance of glucocorticoids in the morphological and functional development of tissues. The aim of this study was to determine time of onset of GR in human tissues using an immunohistochemical method. Results indicate GR are present in tissues of 8–10-week-old human embryos: in most tissues, the immune reaction was only or predominantly nuclear.

Cortisol in human tissues at different stages of life.

Aim of the work was to measure the Cortisol level in human tissues at different stages of life, by means of radioimmunoassay and by chromatography. Viable samples of 13 different tissues were obtained during surgical intervention from 30 to 70 years old patients of either sex. Mean tissue Cortisol concentration was 78±35 ng/g, ranging from 20±10 ng/g in the thyroid to 124±76 ng/g in the kidney. Similar values were measured in the corresponding tissues from not decayed corpses, so that paired values could be mediated. However the pancreas, and corrupted autopsy tissues, gave nil or exceedingly high Cortisol concentration values; in some cases, opposite extreme values were measured in different organs of the same body. Cortisol concentration was also measured in 11 sound different tissues of spontaneously aborted or stillbirth fetuses, between 16 and 36 weeks of gestation. Mean value was 63±27 ng/g, ranging from 30±25 ng/g in the liver to 104±52 ng/g in the lungs. Also in fetuses nil or exceedingly high Cortisol values occurred in altered tissues. One hundred and fourteen samples of limbs and carcasses of 7 to 12 gestational weeks embryos, obtained from voluntary abortions, were also examined: 20% gave nil result, in the remaining mean Cortisol concentration was 32 ng/g. In 33 samples of embryos’ mixed viscera, RIA and chromatography gave unreliable exceedingly high values. The nil and the exceedingly high values measured in the altered autoptic tissue specimens were inconsistent with the Cortisol blood level measured in the patients, as were those measured in embryonic tissues with the acknowledged blood and adrenals Cortisol levels at that stage of life. Thus Cortisol may be measured by RIA and by chromatography in sound tissues, while the values obtained in the pancreas, in corrupted tissues, and in embryonal viscera do not represent the hormonal milieu, but are likely artifacts due to impeachment of the diagnostic system.