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F Escobar del Rey

Publications and source records attributed to F Escobar del Rey.

At least 55 records · Page 3Linked to original sources
PubMed1987

Fetal and maternal thyroid hormones.

It is well known that insufficient production of thyroid hormones during the fetal and neonatal period of development may result in permanent brain damage unless treatment with thyroid hormone is instituted very soon after birth. But congenital hypothyroidism is not the only situation in which brain damage may be related to insufficient thyroid function. Cretinism is the most severe manifestation of iodine deficiency disorders found in areas where iodine intake is greatly reduced. Some of the manifestations of cretinism suggest that the insult to the developing brain starts earlier than in the case of congenital hypothyroidism. Hypothyroxinemia of mothers with adequate iodine intake may also leave permanent, though less severe, mental retardation. For these reasons the possible role of maternal transfer of thyroid hormones during early fetal development have been reinvestigated, using the rat to obtain various experimental models. It has been shown that thyroid hormones are found in embryonic tissues before onset of fetal thyroid function and that thyroidectomy of the mother results in delayed development of the concepta. The concentrations of T4 and T3 in embryonic tissues from thyroidectomized dams were undetectable before the onset of fetal thyroid function, and still reduced in some tissues near term, despite the onset of fetal thyroid function. Treatment of control and thyroidectomized dams with methyl-mercaptoimidazole to block fetal thyroid function reduced thyroid hormone concentrations in fetal tissues near term, but this decrease could be partially avoided by infusion of physiological doses of thyroxine to the mothers. Iodine deficiency of the mothers resulted in thyroid hormone deficiency of the developing embryo, which was very marked until term in all tissues including the brain. The results strongly support a role of maternal thyroid hormones in fetal thyroid hormone economy both before and after the onset of the fetal thyroid function, at least in the rat. They also support a role of the hypothyroxinemia of iodine-deficient mothers in initiating the brain damage of the endemic cretin, a damage which would not be corrected once the fetal thyroid becomes active, as iodine-deficiency of the fetus would impair adequate production of hormones by its own thyroid, and maternal transfer would continue to be low.

Congenital Hypothyroidism↗
PubMed1987

Effects of maternal iodine deficiency on thyroid hormone economy of lactating dams and pups: maintenance of normal cerebral 3,5,3'-triiodo-L-thyronine concentrations in pups during major phases of brain development.

Female rats were fed a diet with a low iodine content (LID), or the same LID supplemented with KI, and mated. Fetuses were obtained at 17 and 21 days of gestation, or pups were killed at different ages after birth. The dams on LID were markedly iodine deficient and developed a large goiter. Their thyroidal iodine content was only 4% of that of LID + I dams. The iodine deficiency of the LID mothers was severe enough to result in very low plasma T4 levels and in hepatic and cerebral T3 deficiency, despite normal circulating levels of T3. The fetuses from LID dams had low concentrations of iodine in their placentas and thyroid glands, and were deficient both in T4 and T3 in all tissues studied, including the brain. After birth, however, suckling LID pups were able to increase the plasma T4 to levels which were higher than those found in either LID fetuses or in adult LID progeny, although plasma T4 was always lower than in age-paired LID + I animals. This increase in T4 was probably due to an approximately 5-fold increase in iodine intake while suckling. Milk from LID mothers was found to contain 22% of the amount of iodine found in milk from LID + I dams, in contrast to their iodine intake, which was about 4% that of the LID + I rats. Cerebral T3 levels were the same for LID and for LID + I pups throughout most of the postnatal period of brain development. This finding might explain the difficulties encountered in obtaining an experimental model of neurological cretinism in rats.

Animals↗
PubMed1986

Effects of maternal iodine deficiency on the L-thyroxine and 3,5,3'-triiodo-L-thyronine contents of rat embryonic tissues before and after onset of fetal thyroid function.

Female rats were placed on a low iodine diet (LID) or LID supplemented with KI. They were mated 3-6 months later. Maternal and embryonic tissues were obtained both before the onset of fetal thyroid function, at 11 and 17 days of pregnancy, and at 21 days of gestation. T4 and T3 concentrations were measured by RIA. T4 concentrations were very low in the plasma, liver, and lung of LID dams and in all embryonic samples obtained from such mothers, namely 11-day-old embryotrophoblasts, 17-day-old placentas and embryos, 21-day-old placentas, embryos, plasma, liver, lung, and carcass (whole embryos minus the trachea, thyroid, blood, liver, and brain). T3 was low in 17-day-old placentas and embryos and in all fetal tissues obtained at 21 days of gestation from LID dams. These results show that when iodine deficiency is severe enough to result in very low maternal plasma T4 levels, embryonic tissues are deficient in T4 and T3 both before and after the onset of fetal thyroid function. This finding might be relevant to the etiopathology of human iodine deficiency disorders.

Animals↗
PubMed1985

Effect of hypothyroidism on the size of spines of pyramidal neurons of the cerebral cortex.

We have previously shown that hypothyroidism produces a decrease in the number of spines counted along the apical shafts of pyramidal neurons of the cortex. Nevertheless, other authors have found that when an animal is subjected to some adverse living conditions the size of the spines decreases, making them invisible to the light microscope. The question arises then of whether the decrease in the number of spines reported by us in hypothyroid animals is real or is due to a shrinking effect. In order to elucidate this question the cross-surface area of dendritic spines of apical shafts belonging to 20- and 60-day-old rats, thyroidectomized at 10 days of age, as well as those of their corresponding controls were measured in different layers of their cortex, studied using conventional electron microscopic techniques. The application of the three-way analysis of variance model to these data has shown us that while the age of the animal produces a definite increase in the size of the spines, hypothyroidism does not produce any change in their size, leading us to the conclusion that the decrease in the number of spines previously reported is due to an actual loss of these elements.

Animals↗
PubMed1985

Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function.

Embryonic tissues were obtained from normal (C) and thyroidectomized (T) rats between 9 and 21 days of pregnancy. We determined the number and weight, as well as the T4 and T3 contents (RIA), of 9- to 12-day-old embryotrophoblasts, of 13- to 21-day-old embryos and placentas, and of liver, lung, and brain from 20- and 21-day-old fetuses. T4 and T3 were found in all samples obtained from C dams, both before and after onset of fetal thyroid function. Despite low levels of both iodothyronines in fetal plasma near term, their concentrations in fetal brain and lung had reached half the maternal values. The T3/T4 ratio in fetal organs was the same, or higher, than in adult rats. Maternal thyroidectomy resulted in a marked decrease of the number and individual weights of viable conceptuses, throughout gestation. Fetal organ weights near term were also decreased, and changes were found in brain DNA and protein concentrations. T4 and T3 were undetectable in all embryotrophoblasts, embryos and placentas obtained from T dams before onset of fetal thyroid secretion. They were still markedly reduced in 21-day-old placentas. Total extrathyroidal contents of T3 and T4 in 20- and 21-day-old fetuses from T dams were also low as compared to those from normal mothers, but individual organs were not affected to the same degree. Thus concentrations were decreased in the carcass (whole embryo minus the trachea + thyroid + liver + lung + brain), but normal in the brain. These results show that maternal hypothyroidism is accompanied by thyroid hormone deficiency of the conceptus before the fetal thyroid functions. After this, alterations of T4 and T3 concentrations persist until term. Development is also delayed. Thus, adverse effects of maternal hypothyroidism may be due, at least in part, to the thyroid hormone deficiency of the embryonic tissues, and not only to the hypothyroid condition of the mother.

Animals↗
PubMed1984

L-thyroxine and 3,5,3'-triiodo-L-thyronine in rat embryos before onset of fetal thyroid function.

T4 and T3 have been measured by RIA in 10-12-day-old rat embryo-trophoblasts, and in 13-20-day-old embryos and placentas, as well as in a few samples of amniotic fluid. Both T4 and T3 were measured after extraction of the samples with ethanol, purification by paper chromatography, anion exchange resin, or both. T4 and T3 could be shown in all samples studied. The amounts of T4 and T3 per conceptus and their concentrations were higher in embryo-trophoblasts and placentas than in 13-18-day-old embryos. The concentrations of T4 and T3 remained fairly constant in the embryos until day 19, when they appeared to increase. The molar ratios of T4 to T3 were 1.4, 8.5 and 103 for embryos, placentas and maternal plasma, respectively. These data show that, for at least one mammalian species, embryonic tissues are provided with T4 and T3 from the earliest date studied, namely 4 days after uterine implantation, and well before onset of thyroid function, which in the rat starts after 17 days gestational age. Such a result suggests that statements denying a possible role of thyroid hormones in early embryogenesis ought to be reconsidered.

Animals↗
PubMed1984

Cerebral hypothyroidism in rats with adult-onset iodine deficiency.

Rats fed chronically a low iodine diet may have low serum T4 and high circulating TSH, despite normal serum T3. As the brain depends to a great extent on intracellular generation of T3 from T4 for its total and nuclear T3, we have carried out two experiments to determine whether the brain of iodine-deficient rats may become hypothyroid, despite normal serum T3 levels. In both experiments we confirmed previous data, showing that the pituitary and liver of iodine-deficient rats with very low plasma T4 levels are hypothyroid as compared to those of animals receiving the same diet supplemented with KI, though not as markedly as animals which had undetectable circulating levels of both T4 and T3 as a consequence of chronic ingestion of KC1O-4, or of surgical thyroidectomy. We have further found that the nuclear T3 content was decreased in the brain of iodine-deficient rats, as compared with the animals on the iodine-supplemented diet. The nuclear to plasma ratios of labeled T3 showed that the uptake of this hormone into liver and brain nuclei is not decreased in the iodine-deficient rats as compared with those on the iodine-supplemented diet. This finding indicates that the decreased liver and brain nuclear T3 contents of iodine-deficient rats are likely to be a consequence of the marked reduction of their T4 pool, leading to decreased amounts of intracellularly generated T3. The number of spines on shafts of pyramidal neurons from the visual cortex of iodine-deficient rats was lower than that of rats fed the same diet supplemented with KI. Their distributions along the shaft were also not the same. Such changes might well be an index of cerebral hypothyroidism, as they are similar to those found after thyroidectomy of adult rats. It is concluded from the present findings that normal circulating T3 levels may not be sufficient to maintain brain euthyroidism in rats fed a diet iodine deficient enough to result in very low circulating T4 levels.

Animals↗
PubMed1983

Nutrition and iodine versus genetic factors in endemic goiter.

Consanguinity has been considered to be the major factor responsible for the high incidence of goiter in the area of Las Hurdes in Spain. However, iodine deficiency was later found to be severe enough to account for endemic goiter, and the presence of cretins in this area. Children from very similar family and socioeconomic backgrounds were found to be on three different nutritional programs, depending on the schools they were attending, and it appeared of interest to determine the effect of nutrition on the goiter incidence in children from the same population. Total iodine, nitrogen and creatinine concentrations were measured in casual urine samples. All three were found to change in parallel in the different subpopulations. They were low in schoolchildren receiving most of their meals at home. Such meals were composed of locally grown food. They were normal in children living in a boarding school, where all of the food is provided from outside the area. They were intermediate in children from a day care center, who received only some meals from an outside source. In the boarding school, goiter incidence was 21%, as opposed to 87% for schoolchildren fed at home. Such results indicate that in this area consanguinity plays a minor role, if any, in the high incidence of goiter.

Adolescent↗
PubMed1983

[Early detection of congenital hypothyroidism. Study of 31,609 determinations].

As a result of congenital hypothyroidism (CH) early detection program carried out in our clinic during the period 1978-1981, 31.609 capillary blood samples (35,7% from newborn infants) were taken on filter paper cards. An evaluation of TSH following the specific radioimmunoanalysis technique was made in all the samples, and an evaluation of T4 whenever TSH values were higher than 25 microU/ml serum. Thirteen cases of CH were detected: nine with permanent H and four with transient H. Two cases of hyperthyrotropinemia were also detected. Frequency of permanent CH in our population is of 1/3.512. Corresponding biochemical data and detailed clinical characteristics detected, including the cost of the procedure are shown. Authors emphasize on possibility of preventing brain damage and subsequent subnormality through early detection and treatment of congenital hypothyroidism, together with a suitable cost-benefit ratio, makes necessary to carry out a nationwide campaign in accordance with those centers already established.

Congenital Hypothyroidism↗
PubMed1982

Thyroxine treatment and recovery of hypothyroidism-induced pyramidal cell damage.

We have previously shown that changes occur in pyramids of area 17 of the rat visual cortex both after thyroidectomy (T) at 10 and at 40 days of age. To assess the effects of thyroxine treatment, instituted at different ages after T, two series of experiments were performed. A : rats were T at 10 days of age and either left untreated, or injected once daily with 1.5 micrograms thyroxine (T4)/100 g body weight. Treatment was started at 12, 15, 20, 30 or 40 days of age. Groups of untreated and T4-treated T rats and of age-paired intact controls were killed at different ages, ranging from 40 to 80 days. B : rats were T at 40 days of age, a group being treated with the same T4 dose starting 30 days after T. These animals, solvent-treated T rats and intact age-paired controls were killed at 90 days of age. The number and distribution of spines along the shaft of Golgi-stained pyramidal cells of the visual cortex were measured and fitted by a mathematical model developed previously. Body weights, pituitary growth hormone contents, plasma thyrotropic hormone, thyroxine and triiodothyronine levels were measured to assess the degree of hypothyroidism. It was found that treatment with T4 of rats T at 10 days of age prevented the alterations of pyramidal cells, provided treatment was started by 12 days of age and euthyroidism was maintained. In rats T at 40 days of age, treatment with T4 had an ameliorating effect despite a delay in onset of treatment of 30 days after T. Whatever the mechanisms which are involved, the present results stress once more the importance of very early treatment of hypothyroid newborns, if permanent cortical brain damage is to be prevented.

Animals↗
PubMed1981

Differential effects of hypothyroidism on the specific uptake of growth hormone and prolactin by the rat liver.

The possible effects of severe hypothyroidism on the specific uptake of ovine PRL (oPRL) and bovine GH (bGH) by the liver have been investigated in the rat. Female rats were thyroidectomized (T). These animals and age-paired controls (C) were injected with less than 20 ng [125I]iodo-oPRL or [125I]iodo-bGH alone or in combination with 100-200 micrograms native oPRL, bGH, or human GH per 100 g BW. The animals were killed at different intervals, and the total 125I was determined in plasma and liver. From these data, the liver to plasma 125I ratio was calculated. In some experiments the proportion of 125I which was soluble in 10% trichloroacetic acid was also determined. The T rats were all severely hypothyroid. A specific uptake of [125I]iodo-oPRL by the liver could be shown for C rats. It was, however, markedly decreased in T rats (in agreement with previous findings showing a decrease of liver lactogenic binding sites) studied in vitro. On the contrary, the specific liver uptake of [125I]iodo-bGH was not decreased in T rats. Some differences were, however, observed between T and C rats with respect to saturation of the liver uptake of bGH and the metabolism of the [125I]iodo-bGH. The amount of native bGH required to reduce the liver to plasma 125I ratio after injection of [125I]iodo-bGH by 50% was smaller (1.5 microgram/100 g BW) in T rats than in C animals (5 microgram/100 g BW). The rate of degradation of the labeled hormone, as far as could be assessed from the increasing solubility of 125I in 10% trichloroacetic acid, was slower in T than in C animals. Present findings indicate that the specific liver uptakes of bGH and oPRL are not affected in the same manner by severe hypothyroidism.

Animals↗
PubMed1981

Presence of L-thyroxine and 3,5,3'-triiodo-L-thyronine in tissues from thyroidectomized rats.

Female rats were killed 15 days, 2 months, and 4 months after surgical thyroidectomy that was followed by injection of 100 microCi 131I. The concentrations of T3 and T4 were measured in tissues (liver, kidney, brain, heart, and hindleg muscle) specific RIAs. Results were compared to those found in intact rats. Thyroidectomy resulted in severe hypothyroidism by 2 and 4 months after the operation, as assessed by undetectable levels of T4 and T3 in unextracted plasma, high circulating TSH, hypothermia, stasis of body weight increase, and depletion of pituitary GH content. Concentrations of T4 and T3 in plasma, as determined after extraction and concentration, were very low, being less than 5% of the normal value by the earliest observation period (15 days). In contrast, although tissue concentrations and total organ contents also decreased after thyroidectomy, they were still clearly detectable 4 months after thyroidectomy. The rates of decrease of T4 and T3 concentrations in most tissues were markedly slower than expected from their rapid decrease in plasma. Some tissues still contained 20% of the normal level 2-4 months after ablation of the thyroid. Tissue levels of thyroid hormones were hardly detectable in rats thyroidectomized 6 months before, having decreased in most tissues to less than 5% of the normal value. Several animals from this group had died. It is concluded that tissues from severely hypothyroid thyroidectomized rats may contain higher concentrations of T4 and T3 than previously thought. The idea that thyroid hormone is not essential for life, based on the assumption that thyroidectomized animals survive without thyroid hormones, might have to be reevaluated.

Animals↗
PubMed1981

A survey of schoolchildren from a severe endemic goitre area in Spain.

All the boys and girls between six and fourteen years old regularly attending school in three villages from an area in Spain known ass Las Hurdes were studied with respect to thyroid size, body weight and height. Casual urine samples were obtained for the determination of iodine and creatine concentrations. Capillary blood was spotted on filter paper and used for the determination of thyroxine and thyrotropin by radioimmunoassay. The same survey was carried out in 354 school children from Madrid, whose data were used as a reference of the adequacy of the methods employed in Las Hurdes. Goitre prevalence was very high, the overall frequency being 86 per cent. The concentration of iodine in the urine was less than 20 micrograms/1 in 71 per cent of the school children. The concentration of creatine in the urine was also half that found in children from Madrid, and the daily creatine excretion in children from Las Hurdes was lower than expected from their body weight. Their somatic development, as measured by height and weight, was retarded markedly, both as compared to the Madrid reference group and to international charts. Serum T4 was less than 78 nmol/l ( micrograms/kl) in 46 per cent, of the children from Hurdes, and serum TSH greater than 7.5 mU/l in 40 per cent. A relatively low stature (below the 10th percentile) was associated with either a low serum T4, an elevated serum TSH, or both, in 30 per cent of the children. These results indicate that the persistence of endemic goitre in Las Hurdes is of great significance and that there is a continuing risk of the birth of cretins. Observations made a decade earlier in the same area show that the goitre endemic is not diminishing, and that an iodization programme is urgently needed. It also appears that a high proportion of the "normal' schoolchildren have features found in hypothyroidism.

Adolescent↗
PubMed1980

Reversible morphological alterations of cortical neurons in juvenile and adult hypothyroidism in the rat.

We have studied: (i) whether or not hypothyroidism induced experimentally in the adult rat affects the number and distribution of spines along the apical shaft of pyramidal cells from the visual cortex; and (ii) whether treatment with thyroid hormone would reverse such changes. Two experiments were performed. Experiment A involved the study of rats which were thyroidectomized (T) at 40 or at 120 days of age, killed at 120 and 220 days of age, respectively, data being compared to those of adequate sex and age-paired controls. Experiment B involved rats which were T at 40 days of age; they were subdivided into two groups, one of which was left untreated and the other received 0.2 microgram of thyroxine/100 g body weight/day for 25 days. Both groups were killed at 90 days of age. We found that: (i) T at 40 and at 120 days of age resulted in a decrease of the number of spines and a derangement of their distribution along the shaft, the observed changes being qualitatively comparable to those previously described for rats T at 10 days of age; and (ii) preliminary results from experiment B indicate that the observed changes in neuronal morphology might be reversible. It is suggested that age-independent and reversible alterations of learning capacity and electrocortical activity of hypothyroid rats might have age-independent and reversible morphological correlates at the level of the cortex.

Age Factors↗
PubMed1980

Evidence against a major role of L-thyroxine at the pituitary level: studies in rats treated with iopanoic acid (telepaque).

To determine whether T4 has an intrinsic effect at the pituitary level, it would be important to block conversion of T4 to T3 completely. We have attempted to achieve this with iopanoic acid (IOP), a radiographic contrast agent. We have then measured in the same animals the effects of such treatment on the conversion of T4 to T3 or on the deiodination of T3 and on the pituitary response to a dose of T4 or T3. Plasma TSH levels and pituitary GH content were measured as biological end points. Thyroidectomized rats were injected with a single dose of T4 (1.7 micrograms/100 g BW) labeled with [125I]T4 (Exp A) or with a single dose of T3 (0.33 microgram/100 g BW) labeled with [125I]T3 (Exp B) and treated with IOP or solvent. Animals of Exp A were killed 24 h after iodothyronine injection and those of Exp B were killed 4, 12, and 24 h after injection of the iodothyronine. The concentrations of [125I]T4 and [125I]T3 were measured in several tissues, including the anterior pituitary, after extraction and paper chromatography and quantified with the aid of 131I-labeled markers added in vitro. Plasma and pituitary T3 and T4 plasma TSH, and pituitary GH were measured by specific RIAs. Results show that treatment with IOP markedly inhibits the conversion of T4 to T3 and the deiodination of T3. In IOP-treated thyroidectomized rats, the injection of T4 results in little, if any, effect at the pituitary level, despite an almost 3-fold increase in the percentage of injected T4 found in the gland. Treatment with IOP does not inhibit the effects of a T3 dose; if anything, they appear to be enhanced. It is concluded that, as assessed from biological responses involving the anterior pituitary, a dose of T4 has little if any effect other than that which can be attributed to the T3 generated from it.

Animals↗
PubMed1979

Severe hypothyroidism and the maturation of the rat cerebral cortex.

In order to study the influence of hypothyroidism on the maturation of the visual cortex, rats were thyroidectomized (T) surgically at 10 days of age and injected with 131I within 2 days after the operation. These T rats, and age-paired controls (C), were killed at 20, 25, 30, 40 and 80 days of life. The groups of T rats were subdivided into 'severely' hypothyroid and hypothyroid animals, on the basis, respectively, of complete or incomplete stasis of body growth and depletion of pituitary growth hormone stores. The pyramidal cells of the visual coretx of 'severely' hypothyroid rats were studied separately from those of hypothyroid animals. It was found that the number of spines along the apical shaft of such cells was markedly and equally reduced in all of the T rats, as compared to C rats, irrespective of the degrees of hypothyroidism attained, and stopped increasing in number by 30 days of age. From this age onwards, the distribution of the spines could no longer be fitted by a mathematical model31 which, however, adequately described for normal rats the developmental changes which take place with increasing age in the distribution of spines along the shaft of pyramidal cells from the visual cortex. This lack of fit was only found for the 'severely' hypothyroid animals; data from the other hypothyroid animals could still be fitted by the model. Such data show that the above-mentioned model31 may be a useful tool for the study of the intensity of the effects of hypothyroidism on the maturation of cortical neurons.

Age Factors↗
PubMed1979

Exchange of triiodothyronine derived from thyroxine with circulating triiodothyronine as studied in the rat.

At present it is widely assumed that T3 derived from T4 is rapidly and totally exchangeable within the volume of distribution of T3 secreted by the thyroid into the bloodstream. This concept is implied when conclusions are drawn from comparisons between a biological effect in a responsive tissue and circulating T3 and T4 levels. Such conclusions are often in conflict with those derived by comparing the biological effect with the concentrations of T3 and T4 in the responsive tissue itself. Thus, it appeared important to test the above assumption directly. Thyroidectomized rats have been treated for 4-4 1/2 days with a mixture of 131I labelled T4 (131T4) and 125I labelled T3 (125T3), which was either injected twice daily or administered by continuous i.v. infusion. The rats were bled, perfused, and their plasma and tissues submitted to extraction and paper chromatography. If the tested assumption were correct, the ratio between the T3 derived from T4 and the T3 injected as such (namely, the 131T3/125T3 ratio) should be the same in plasma, liver, kidney, heart, muscle, etc. It was evident that the 131T3/125T3 ratio was not the same for different tissues. The differences were not merely due to artefactual deiodinations. The presence of small amounts of 131I and 125I containing compounds in the T3 spot was considered as highly unlikely, though not totally excluded. The data thus suggest that T3 derived from T4 and the injected (or thyroidally secreted) T3 might not be totally exchangeable within an observation period which is considerably longer than the one for which complete equilibrium was previously assumed. If so, changes in the size of the T4 pool, or in the rate of T4 conversion to T3, might affect the concentration of T3 in a given tissue to an extent not disclosed from the circulating T3 levels alone. Several possible consequences of the present findings are discussed.

Animals↗