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F Escobar del Rey

Publications and source records attributed to F Escobar del Rey.

At least 37 records · Page 2Linked to original sources
PubMed1994

Thyroid hormones in tissues from fetal and adult rats.

Concentrations of T4 and T3 were recently measured in rat fetal tissues, and the reported values were found to be more than 10-fold higher than those found by us. The differences have been explained by the assumption that previous analytical procedures, neither avoid deiodination during autopsy of the animals or during extraction and purification, because phloretin [(3'),4',4,6-(tetra)trihydroxyaurone], a potent inhibitor of 5'-iodothyronine deiodinase activity in vitro, had not been used to prevent such problems. We here show that perfusion with phloretin during autopsy does not affect 5'-iodothyronine activity or T4 and T3 concentrations in liver, kidney, or brain. Evidence is also provided that the addition of phloretin during the homogenization process is superfluous, as the use of 80% ethanol and 0.02 M NaOH for this step results in undetectable deiodinase activity. Data are presented showing that during the final sample drying, no losses or degradation of T4 and T3 occur, confirming the adequacy of the individual recovery corrections using radiolabeled iodothyronines as internal tracers. We also present quantitative information on the intralaboratory variability of the T4 and T3 concentrations found in tissues from normal fetuses and their mothers as well as in adult males and nonpregnant females. Results are comparable to those obtained by others using entirely different analytical procedures.

Animals↗
PubMed1993

Effects of iodine deficiency on thyroid hormone metabolism and the brain in fetal rats: the role of the maternal transfer of thyroxin.

Thyroid hormones, thyroxin (T4) and 3,5,3'-triiodothyronine (T3), of maternal origin, are available to the mammalian embryo early in development. However, after the onset of fetal thyroid function, they are of both fetal and maternal origin. Maternal T4 has a protective effect on the fetal brain in cases of congenital hypothyroidism. In severe iodine deficiency, maternal T4 is low, although T3 is normal; the developing embryo is markedly T4-deficient; and T3 deficiency increases with gestational age. In contrast to mechanisms in the hypothyroid fetus from a normal mother, the low T4 of the iodine-deficient mother prevents any protective effects on the fetal brain. Thyroid hormone deficiency of the iodine-deficient fetus, including the brain, is more severe and prolonged than it is in the cases of maternal or fetal thyroid failures. These findings may help to explain the relationship between severe maternal hypothyroxinemia and the severe central nervous system damage of the neurological endemic cretin.

Animals↗
PubMed1993

Differential effects of thyroid hormones on growth and thyrotropic hormones in rat fetuses near term.

We have studied the effects of thyroid hormone deficiency and excess on GH and TSH economy in the rat fetus near term. Pregnant rats were either left untreated (C group) or treated with methimazole to block thyroid function and infused with placebo, T4, T3, or both, until 21 days of gestation. Two experiments were performed: the doses (per 100 g body wt/day) of T4 ranging from 2.4-21.6 micrograms, those of T3 from 1.5-13.5 micrograms, with groups on 2.4 micrograms T4 + 1.5 micrograms T3. Fetal plasma T4 levels varied between 6-160% of C values and T3 values between 52-770%. Both plasma and pituitary GH decreased in hypothyroid fetuses from methimazole dams, and their plasma TSH was elevated. When T4 and/or T3 were infused, plasma and pituitary GH increased as a function of fetal plasma T4 and T3, reaching normal values when plasma T3 levels became normal, then increasing further. The effects on GH economy were related to the plasma T3 level, with no appreciable difference if T3 had been infused or derived from T4. In contrast, the elevated plasma TSH of the hypothyroid fetus decreased toward normal values when fetal plasma levels of T4, and of T3 derived from T4, became normal, but was not affected by normal fetal plasma T3 when T3 was infused. In the absence of T4, T3 decreased plasma TSH only when infused in doses that increased fetal plasma T3 3-fold above C values or more. Thus, both GH and TSH economy are under thyroid hormone control in rat fetuses near term. Similarities and differences with respect to regulation in adult rats cannot, however, be attributed exclusively to differences in fetal somatotrophs and thyrotrophs, because of the possibility that control is exerted at regulatory sites which are unique to the fetus.

Animals↗
PubMed1992

The rat placenta and the transfer of thyroid hormones from the mother to the fetus. Effects of maternal thyroid status.

We have studied the effects of maternal thyroid status on the effectiveness of the rat placenta near term as a barrier for the transfer of T4 and T3 to the fetus. Dams were given methimazole to minimize the fetal contribution to the T4 and T3 pools, so that the iodothyronines found in the conceptus are ultimately of maternal origin. The dams were infused with saline, or with T4 or T3 at doses ranging from 2.3-27.8 nmol T4 and from 0.77-20.7 nmol T3/100 g BW per day. A group of normal pregnant dams (C) was included. At 21 days of gestation T4, T3, and rT3 were measured by RIA in maternal and fetal plasma, and in maternal and fetal sides of the placenta. The total fetal extrathyroidal T4 and T3 pools were also determined. The dose-related changes in T4, T3, and rT3 levels in the placenta confirm the presence of both inner and outer ring iodothyronine deiodinase activities, and suggest increasing accumulation of the iodothyronines. Despite this, fetal extrathyroidal T4 and T3 increase progressively in T4-infused groups as a function of maternal circulating T4 levels. Fetal extrathyroidal T3 increases progressively in T3-infused groups as a function of maternal plasma T3. There was no evidence that the net maternal contribution of T4 or T3 would be proportionally less when the maternal pools became very high. It was concluded that the rat placenta is only a limited barrier for the transfer of T4 and T3 to the fetus.

Animals↗
PubMed1992

Homeostasis of brain T3 in rat fetuses and their mothers: effects of thyroid status and iodine deficiency.

Faced with large variations in iodine, T4 or T3 supply, the fetal brain is able to maintain T3 homeostasis to a greater degree than apparent from changes in plasma and other tissues, such as the liver. Changes in the activity of 5'D-II play an important role in this homeostasis, although this does not exclude other regulatory mechanism(s), such as changes in type III (5D) activity, in uptake of the iodothyronines by the brain, or in cerebral iodothyronine turnover rates. T3 generated locally from T4 is more important than plasma derived T3 as determinant of the total T3 available to the brain throughout the life cycle of the rat. It is especially important during the fetal and neonatal phases of brain development, when the brain depends almost exclusively on the supply of T4. Fetal brain T3 homeostasis is maintained despite large fluctuations in the supply of T4. An excess of T3 also affects brain T3 to a lesser degree than it does other tissues. If present results are relevant to man, they suggest that overtreatment of mother of a congenital hypothyroid fetus with T4 is not likely to be harmful for the fetal brain. Treatment with T3 should be avoided, as it deprives the fetal brain of the main regulatory mechanism involved in homeostasis of brain T3, namely generation of T3 from T4.

Animals↗
PubMed1991

Maternal hypothyroidism and fetal chondro-osseous development in rats.

The bone development of rat fetuses from female Wistar rats thyroidectomized prior to mating was studied, between 16 and 21 days of gestation. The parameters studied in each rat fetus were fetal weight, number of fetuses per litter, radiological data and frequency of appearance of ossification centers, diaphyseal radiological length of long bones, longitudinal ratio between epiphysis and diaphysis of long bones on cleaned and stained limbs, and volumetric tibial studies on the same limbs. Our results show a delay of fetal chondro-osseous development and a delay of weight increase in fetuses from thyroidectomized rats. After onset of fetal thyroid function, the fetal development begins a catch-up growth, which is not sufficient to completely overcome development delay prior to birth.

Animals↗
PubMed1991

Thyroid hormones and 5'-deiodinase in the rat fetus late in gestation: effects of maternal hypothyroidism.

Having previously observed that T4 and T3 levels in fetal rat brain and brown adipose tissue are clearly higher than expected from their low circulating levels, we have now studied thyroid hormone concentrations and 5'-deiodinase activities (5'D) in several other rat fetal tissues during the last 6 days of gestation (dg), namely 17-22 dg. This period comprises the onset of fetal thyroid activity. Total thyroidal T4 and T3 contents increased 100- and 400-fold, respectively; T4 concentrations increased 8- to 10-fold in plasma, carcass, lung, and liver, and T3 increased 4.5- to 9-fold, except in plasma and liver, where T3 levels increased less than 2-fold in plasma and 3-fold in liver. During this developmental period 5'D activity increased 5- and 10-fold in fetal liver and lung, respectively. In fetuses from hypothyroid [thyroidectomized (T)] dams, body weight was lower than in fetuses from normal dams. Total thyroidal T4 and T3 contents were initially the same, but decreased markedly in fetuses from T dams by the end of gestation. At the earliest fetal ages studied (17-18 dg) T4 and T3 concentrations were lower in carcass, liver, lung, and brain, although near term there were no consistent differences between the fetal tissues from T and control dams, probably because of compensatory stimulation of thyroidal secretion. Liver 5'D was decreased by 50% throughout gestation, and lung 5'D activities were lower by the end of gestation. Thyroid hormones in placentas from T dams were very low, but increased by the end of gestation because of the contribution by the fetal thyroid. Present results describe the ontogenic profiles for thyroid hormone concentrations and 5'D activities during late fetal development; active regulatory mechanisms are already present at this age. It has been frequently stated that rat fetuses near term are deficient in thyroid hormones, and that their thyroid hormone economy is independent of maternal thyroid status, but present results show that near term, T4 and T3 concentrations in several tissues reach levels that are 50% or more of those described for adult animals, and that fetal thyroid function is influenced by maternal hypothyroidism.

Animals↗
PubMed1991

Outer ring iodothyronine deiodinases and thyroid hormone economy: responses to iodine deficiency in the rat fetus and neonate.

Female rats were fed a low iodine diet (LID) or the same diet supplemented with KI (IOD) and mated. Plasma TSH, T4 and T3 in thyroid, plasma, and tissues, and 5'-deiodinase activities (5'D) were measured in maternal, fetal, and neonatal samples. Plasma T4 was markedly reduced in LID dams, TSH was increased, and T3 was normal. Placental T4 was decreased to 10%, and placental T3 to 50%. In LID fetuses there was a complete depletion of both extrathyroidal and intrathyroidal stores of T4 and T3. The thyroid responded with increased synthesis and secretion of T3 over T4, as assessed from the T3 to T4 ratios. Near birth, brain T4 and T3 concentrations were only 6.7% and 12% of those in IOD fetuses, despite a marked increase in brain 5'D-II and a T4-sparing decrease in liver and lung 5'D-I. Brown adipose tissue 5'D-II increased 7-fold, and brown adipose tissue T4 and T3 concentrations were only decreased by 50%. After birth, the availability of iodine improved somewhat through maternal milk, and the thyroidal and extrathyroidal pools of T4 and T3 increased, although they remained much lower than those in IOD pups. Brain 5'D-II markedly increased in LID pups, and this together with an increase in plasma and brain T4 ensured almost normal brain T3 during the suckling period. The thyroidal secretion of T3 over T4 continued to be increased in LID pups during the suckling period and appeared to be related to their high circulating TSH levels. Both LID fetuses and newborns can respond to iodine deficiency as adults rats, but the fetus is more sensitive to LID because of its dependence on maternal T4. The success of the adaptative mechanisms in protecting the brain from severe T3 deficiency depends on the supply of iodine, the limiting factor for the synthesis of T4.

Animals↗
PubMed1990

Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain.

To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be clinically euthyroid if their T3 levels are normal.

Animals↗
PubMed1989

Thyroid hormones and 5'-deiodinase in rat brown adipose tissue during fetal life.

Brown adipose tissue (BAT) iodothyronine 5'-deiodinase (5'D) activities are very high during fetal life but decrease 10-fold a few hours before birth. Accordingly, BAT 3,5,3'-triiodothyronine (T3) concentrations are also very high. The temporal patterns of changes in BAT 5'-D and fetal plasma insulin are similar (and differ from the pattern for catecholamines) but are not superimposable. A causal role for insulin in the activation of fetal BAT 5'-D is therefore not supported by the data. Maternal thyroidectomy leads to a decrease in the total and relative weight of fetal BAT and to a 30-50% increase in BAT 5'-D activities; BAT thyroid hormone concentrations are essentially unchanged. Fetal hypothyroidism was induced by giving methimazole and resulted in a marked decrease of BAT thyroxine (T4) and T3 concentrations. This treatment increased BAT 5'-D activity only on day 21 of gestation, but no effect was observed on day 20. The fetal 5'-D response to thyroid hormones infused into the methimazole-treated dams was studied at 21 days of gestation. The increase in BAT 5'-D induced by methimazole treatment was prevented by T4 infused into control dams but not by T3. In fetuses from thyroidectomized dams, the pattern of 5'-D regulation by thyroid hormones was impaired. It is suggested that the high concentrations of thyroid hormones present in fetal BAT might participate in the general maturation and development of fetal BAT.

Adipose Tissue, Brown↗
PubMed1989

Comparison of maternal to fetal transfer of 3,5,3'-triiodothyronine versus thyroxine in rats, as assessed from 3,5,3'-triiodothyronine levels in fetal tissues.

Thyroxine (T4) is transferred from the mother to the hypothyroid rat fetus late in gestation, mitigating T4 and T3 deficiency in fetal tissues, the brain included. We have now compared the effects of maternal infusion with T3. Normal and thyroidectomized rats were started on methimazole (MMI) on the 14th day of gestation, given alone, or together with a constant infusion of 0.45 micrograms (0.69 nmol) T3 or of 1.8 microgram (2.3 nmol) T4/100 g per day. Maternal and fetal samples were obtained at the 21st day of gestation. The doses of T3 and T4 were biologically equivalent for the dams, as assessed from maternal plasma and tissue T3, and plasma TSH levels. MMI blocked the fetal thyroid; T4 and T3 levels were low in all fetal tissues, and fetal plasma TSH was high. Maternal infusion with T4 mitigated both T4 and T3 deficiency in all fetal tissues, the brain included, and decreased fetal plasma TSH. In contrast, infusion of T3 normalized fetal plasma T3 and increased the T3 levels in several tissues, but not in the brain. Neither did it decrease the high fetal plasma TSH levels. The results show that when the fetus is hypothyroid, T3 crosses the rat placenta at the end of gestation, but does not affect all tissues to the same degree. In contrast to the effects of maternal T4, maternal T3 does not alleviate the T3 deficiency of the brain or, presumably, of the thyrotrope. Thus, end-points of thyroid hormone action related to TSH release should not be used to measure transfer of maternal T3 to the fetal compartment. Moreover, T4 should be given, and not T3 to protect the hypothyroid fetal brain.

Animals↗
PubMed1989

Generalized deficiency of 3,5,3'-triiodo-L-thyronine (T3) in tissues from rats on a low iodine intake, despite normal circulating T3 levels.

Rats fed a low iodine diet have decreased total and nuclear T3 concentrations in the liver and brain, as compared with rats supplemented with iodine, possibly because of the very low plasma and tissue T4 pools in low-iodine diet rats, leading to decreased intracellular generation of T3 in those tissues. If so, T3 levels should not decrease in heart and skeletal muscle, as plasma T3 is normal in low-iodine diet rats and these two tissues derive their intracellular T3 directly from plasma T3. We have studied this point in male rats fed a low-iodine diet, a low-iodine diet + iodine, and the stock diet. As in previous studies, low-iodine rats had very low plasma T4 and high plasma TSH levels, plasma T3 levels being normal. Liver T3 decreased, and so did the brain T3 levels despite a compensatory increase in type II 5' iodothyronine deiodinase activity. Contrary to expectations, T3 concentrations were lower in the heart and skeletal muscle of low-iodine diet rats. Attempts to clarify the possible mechanism(s) involved have been unsuccessful so far. The present results show that, despite normal plasma T3, a deficiency of T3 occurs in more tissues of rats on a low iodine intake than previously assumed. If the present results are pertinent to inhabitants from areas with severe iodine deficiency, it would appear that they might suffer from a generalized tissue T3 deficiency (and hypothyroidism?), even if overt clinical signs are not usually present.

Animals↗
PubMed1988

Rapid effects of adult-onset hypothyroidism on dendritic spines of pyramidal cells of the rat cerebral cortex.

We have previously shown (Ruiz-Marcos et al. 1980, 1982) that thyroidectomy (T) performed in rats at 40 days of age, well past the neonatal period of development, results by 80-90 days of age in a decrease of the number of spines along the shaft of pyramidal neurons with the cell body in layer V in the visual area of the cerebral cortex. We have here studied how soon after the operation an effect on spine number and distribution may be observed. We have found that the response of these neurons to T is very rapid: a decrease in the number of spines/shaft between T and age-paired controls (C) rats is statistically significant by the earliest period of observation, namely 5 days after T. These results may be related to those of Dembri et al. (1983) showing that T performed in adult rats decreases the activity of Type I RNA polymerase by 5 days after the operation. It is possible that T impairs the synthesis of some compound(s) necessary for the formation and maintenance of spines. The present results suggest that spine number is not a fixed structure of the apical shaft once brain development is over, but is in a state of continuous formation and degradation. We have further observed that the effect of T performed at 40 days of age is more pronounced in the distal part of the shaft than on the rest, a result similar to that found after neonatal T (Ruiz-Marcos et al. 1982). However, contrary to findings after early hypothyroidism, T at 40 days of age does not distort the distribution of spines along the shaft.

Animals↗
PubMed1988

Developmental changes in rat brain 5'-deiodinase and thyroid hormones during the fetal period: the effects of fetal hypothyroidism and maternal thyroid hormones.

We have studied the ontogenesis of 5'-deiodinase (5'D) activity in rat brain during fetal life, its capacity to respond to maternal or fetal hypothyroidism, and its regulation by maternal thyroid hormones. Type II 5'D (5' D-II) activity increases 4-fold during the period studied (17 to 22 days of gestation), mainly between days 19 and 21. Fetal brain T4 concentrations increase in parallel with fetal plasma T4, whereas fetal brain T3 concentrations increase 18 times (days 17-21), six times more than would have been expected from the small increase in fetal plasma T3 levels. Maternal thyroidectomy did not affect 5'D-II activity or thyroid hormone concentrations in fetal brain (except brain T4 at 18 days of gestation). Fetal hypothyroidism, induced by giving a goitrogen (methimazole) to the mothers, depleted all fetal tissues studied, including the fetal thyroid, from thyroid hormones. By 19 days of gestation, the fetal brain was able to respond to hypothyroidism with a 3- to 5-fold increase in 5'D-II activity. Earlier onset of treatment with methimazole led to 2- to 3-fold increases in 5'D already at 17 and 18 days of gestation, showing that when fetal thyroid secretion starts the fetal brain 5'D-II is able to respond to hypothyroidism. Replacement of methimazole-treated mothers with physiological doses of T4, given by constant infusion, increased T4 and T3 concentrations in fetal brain, and inhibited fetal, as well as maternal, brain 5'D-II activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Transfer of thyroxine from the mother to the rat fetus near term: effects on brain 3,5,3'-triiodothyronine deficiency.

It has recently been shown that thyroid hormones are transferred from the mother to the developing rat embryo early in gestation, before the onset of fetal thyroid function. We have now studied whether there is transfer of T4 from the mother to the fetus late in gestation when the fetal thyroid is impaired. Normal and thyroidectomized females were mated, given a goitrogen [methimazole (MMI)], starting before the onset of fetal thyroid function and until term, alone or together with a constant infusion of T4 (1.8 micrograms/100 g BW.day). T4 and T3 were determined by RIA in several maternal samples and in tissues from 21-day-old fetuses. The administration of MMI blocked the fetal thyroid, as assessed from the decreased thyroid concentrations of T4 and T3. The concentrations of both iodothyronines also decreased in placenta, thyroid, plasma, brain, liver, lung, and carcass of fetuses from MMI-treated dams. Infusion of T4 into such MMI-treated mothers partly avoided this decrease, and T4 levels increased in all fetal tissues to 41-57% of those in normal fetuses. In contrast to this, T4 infusion affected the concentration of T3 to varying degrees in different tissues. The T3 concentration in plasma and lung increased very little when the MMI-treated mother was infused with T4, but in the brain T3 reached concentrations comparable to those in normal fetuses. Results not only show transfer of T4 from the mother to the fetus near term, at least when the fetal thyroid is impaired, but also suggest that it might mitigate, or avoid, the adverse effects of such failure on the developing brain.

Animals↗
PubMed1988

Maternal-fetal thyroid hormone relationships and the fetal brain.

Thyroid hormones are transferred from the mother to the fetus. Thus, despite the deiodinating enzymes of the placenta (26), some T4 and T3 is transferred, both before and after onset of fetal thyroid function, at least in those cases where fetal thyroid function is impaired. It is also possible that transfer occurs under normal conditions. Maternal to fetal transfer of T3 and T4 is partially limited. But it might be enough to mitigate severe fetal T4 and T3 deficiencies. However, the mitigating effects of both hormones are not equivalent for all fetal tissues. 1) Maternal T4 mitigates T4 and T3 deficiency of most fetal tissues, the brain included. 2) Maternal T3 mitigates T3 deficiency only in some fetal tissues, the brain being excluded. It does not mitigate cerebral T3 deficiency even at doses which are toxic for the mother, and it does not depress fetal plasma TSH. 3) Normal maternal thyroid function is important for fetal development. Maternal hypothyroxinemia is damaging to the developing fetal brain early in gestation. It might also later have adverse effects in gestation, if the fetal thyroid is impaired. Normal maternal T3 levels might avoid overt hypothyroidism of some fetal tissues, but is of no benefit to the brain.

Animals↗
PubMed1987

Pyramidal cortical cell morphology studied by multivariate analysis: effects of neonatal thyroidectomy, ageing and thyroxine-substitution therapy.

The changes produced on the whole dendritic morphology of layer III cortical pyramidal neurons by neonatal hypothyroidism, induced in rats by thyroidectomy at 10 days of age (T), as well as those changes related to ageing, have been studied in rats at 40 and 80 days of age. For these purposes, the dendritic structure of these neurons was defined by a set of 10 variables whose measurements were analyzed using multivariate methods. The effect of tyroxine (T4) substitution therapies applied to T rats between 12-40 and 30-80 days of age has been further investigated with the same mathematical methodology. The results obtained from the analyses performed show that hypothyroidism affects both the apical tuft and the basal dendritic arborization of these neurons. The observed damage was similar: a decrease of the total length of the dendritic segments of the apical tuft and the basal arborization. This change, however, was detected in these two different subregions with a different timing. These results seem to reinforce our findings concerning the selective effect of T on different sites of these neurons. On the other hand, 3 morphological changes have been revealed regarding the development of the pyramidal neuron studied: (1) the total length of the apical tuft dendritic segments increases from 40 to 80 days of age; (2) the total length of the basal dendritic segments decreases from 40 to 80 days of age; and (3) the perimeter of the cell body decreases from 40 to 80 days of age. Finally, the results obtained did not allow us to detect any recovery of the damage induced by T, as a consequence of the T4 substitution therapies applied.

Aging↗