Biomedical subjects

M J Obregon

Publications and source records attributed to M J Obregon.

At least 19 recordsLinked to original sources

PubMed1998

Immunohistochemical and morphometric studies of the fetal pancreas in diabetic pregnant rats. Effects of insulin administration.

BACKGROUND: Maternal diabetes influences fetal pancreas development. As there are some controversial reports, we studied the morphometric changes of the fetal insular pancreas and insulin immunostain of beta cells as well as the proliferative activity of insular cells in 21-day-old fetuses from control, diabetic, and insulin-treated diabetic pregnant rats. METHODS: Streptozotocin was injected into 7-day-pregnant rats (controls were not injected). Some rats were either left untreated (diabetic) or injected with insulin. Animals were killed at 21 days of gestation. Fetal pancreas were fixed in toto for the morphometry and immunohistochemistry studies using anti-insulin, anti-Ki-67 and anti-proliferating cell nuclear antigen (PCNA) antibodies. RESULTS: Diabetic status was determined by measuring maternal and fetal serum glucose and insulin levels. The morphometric studies showed hyperplasia of the diabetic fetal insular tissue which had not been normalized by insulin therapy. Diabetes caused an increase of both insulin-positive and insulin-negative cells. The increase in insulin-positive cells was not corrected by insulin treatment, although the number of non-beta cells became normal. The nuclear area in beta cells increased in diabetic rats but was not corrected by insulin. The cytoplasmic area decreased in diabetic rats and was normalized by insulin administration. Diabetes increased the expression of the nuclear antigen Ki-67 in fetal insular pancreas, and insulin treatment returned it to the normal state. CONCLUSIONS: Maternal diabetes leads to hyperstimulation of fetal beta cells, with increased proliferative activity. Insulin administration to the dams corrects some of the changes observed.

Animals↗

PubMed1993

Regulation of malic-enzyme-gene expression by cAMP and retinoic acid in differentiating brown adipocytes.

Brown adipose tissue (BAT) is composed of highly specialized cells, whose main function is to produce heat under adrenergic stimulation, uncoupling oxidative phosphorylation. For this function, lipogenesis must be accurately regulated. Malic enzyme has a central role in lipogenesis and is strongly expressed in brown adipocytes. In this work, we study the modulation by adrenergic stimuli, cAMP effectors and retinoic acid on the induction produced by insulin and 3,5,3'-triiodothyronine on malic-enzyme-gene expression. Primary cultures of differentiating brown adipocytes have been used. The results obtained demonstrate that physiological doses of norepinephrine do not modify malic-enzyme mRNA levels when acting alone, but considerably reduce the induction produced by insulin, 3,5,3'-triiodothyronine or both together. Other cAMP inducers such as glucagon, forskolin or 8-bromo-cAMP, greatly inhibit both, basal and 3,5,3'-triiodothyronine-induced malic-enzyme-gene gene expression. Retinoic acid abolishes basal and also inhibits 3,5,3'-triiodothyronine-induced malic-enzyme-gene expression.

8-Bromo Cyclic Adenosine Monophosphate↗

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↗

PubMed1993

Multiple regulation of S14 gene expression during brown fat differentiation.

S14 is a gene known to be under thyroid hormone control. Its mRNA concentration is very high in lipogenic tissues, and although the precise function of the protein is still unknown, indirect data suggest its implication in triglyceride synthesis. S14 gene expression is up-regulated by thyroid hormone in liver, white adipose tissue, and lactating mammary gland. However, in brown fat, the level of this sequence is increased 3-fold in the hypothyroid animal. We have used primary cultures of brown preadipocytes differentiated to fully mature brown adipocytes to investigate the influence of cellular differentiation and hormonal stimulation on S14 gene expression. Steady state levels of S14 mRNA rose from nondetectable levels in preadipocytes to reach a maximum in fully mature adipocytes. Treatment of brown adipocytes cultures with T3 did induce S14 gene expression. This induction reflects in part a posttranscriptional stabilization of the messenger by T3. Insulin, insulin-like growth factor-I, and inositol phosphate-glycan also increase the level of S14 mRNA. Norepinephrine (NE) plays a major role in the regulation of S14 gene, and 24 h after its addition, NE elicited a 20-fold decrease in mRNA S14 concentrations. An elevated intracellular concentration of cAMP is a strong negative effector of S14 gene expression, and neither NE nor cAMP action is totally overcome by T3. As happens in vivo, glucose is a potent stimulator of S14 mRNA; however, there is a lag time of several hours before its effects can be detected. The increase in S14 gene expression with the maturation stage of the cell suggests an important role for S14 in adipocyte differentiation.

Adipose Tissue, Brown↗

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↗

PubMed1990

Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term.

Normal dams were equilibrated isotopically with [125I]T4 infused from 11 to 21 days of gestation, at which time maternal and fetal extrathyroidal tissues were obtained to determine their [125I]T4 and T4 contents. The specific activity of the [125I]T4 in the fetal tissues was lower than in maternal T4 pools. The extent of this change allows evaluation of the net contribution of maternal T4 to the fetal extrathyroidal T4 pools. At 21 days of gestation, near term, this represents 17.5 +/- 0.9% of the T4 in fetal tissues, a value considerably higher than previously calculated. The methodological approach was validated in dams given a goitrogen to block fetal thyroid function. The specific activities of the [125I]T4 in maternal and fetal T4 pools were then similar, confirming that in cases of fetal thyroid impairment the T4 in fetal tissues is determined by the maternal contribution. Thus, previous statements that in normal conditions fetal thyroid economy near term is totally independent of maternal thyroid status ought to be reconsidered.

Analysis of Variance↗

PubMed1990

Thyroid hormone economy in pregnant rats near term: a "physiological" animal model of nonthyroidal illness?

We have studied the changes in thyroid hormone economy that occur in normal pregnant rats between 17-22 days of gestation. T4 and T3 decreased in all extrathyroidal tissues studied, namely plasma, liver, kidney, lung, heart, and skeletal muscle. The exception is the concentration of T3 in cerebral cortex, which remains unchanged, possibly as a consequence of an increase in type II 5'-iodothyronine deiodinase activity. The marked decrease observed in most T4 and T3 pools was not accompanied by a commensurate increase in circulating TSH levels, which at 21 days gestation were either unchanged or actually decreased. The TSH response to TRH appeared to be prolonged. alpha-Glycerophosphate dehydrogenase activity was decreased in the liver, in accordance with its thyroid hormone deficiency. Hepatic type I 5'-iodothyronine deiodinase activity, however, did not decrease, but was slightly increased. Thus, thyroid hormone economy in the pregnant rat near term shows striking similarities with several (but not all) of the changes described in patients with nonthyroidal illness and in several animal models used to study this condition. It is suggested that attenuation of the negative feedback response to the decrease in thyroid hormone pools, leading to low levels of thyroid hormones in most tissues, is the normal physiological response to situations where preservation of energy (and protein) represents a distinct adaptive advantage, as in the case of the pregnant rat and her conceptus.

Animals↗

PubMed1989

Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein thermogenin: effects of hypothyroidism and norepinephrine.

Expression of the gene for the brown-fat specific uncoupling protein thermogenin was investigated in cell cultures by hybridization of isolated RNA with a cDNA clone corresponding to mouse thermogenin. The RNA was isolated 3-4 days after confluence from cells differentiated in culture from precursors isolated from the interscapular brown adipose tissue of 5-week-old mice. Very low thermogenin mRNA levels were found in cells derived from untreated mice, and there was only little effect of added norepinephrine on thermogenin gene expression in these cells. However, in cells derived from hypothyroid (methimazole-treated) mice there was a higher expression of thermogenin, and norepinephrine had a marked augmenting effect on the thermogenin mRNA level in these cells. These effects of thermogenin mRNA levels were specific, in that they contrasted with the effects of hypothyroidism and norepinephrine on the level of other mRNA species in these cells (coding for beta-actin, lipoprotein lipase, cytochrome-c oxidase, and glycerol-3-phosphate dehydrogenase). It was concluded that brown-fat cells in culture can reach a differentiated state, sufficiently advanced that the unique properties of these cells can be expressed, and that thermogenin gene expression (i.e., the level of thermogenin mRNA) is under direct control of norepinephrine.

Actins↗

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

Euthyroid status is essential for the perinatal increase in thermogenin mRNA in brown adipose tissue of rat pups.

The amount of mRNA coding for the brown-fat specific, uncoupling protein thermogenin was followed perinatally in fetuses and newborns from normal and hypothyroid rat dams. Although the growth of the fetuses and newborns was normal in the hypothyroid group, they had a lower amount of thermogenin mRNA already in-utero, and the dramatic postnatal increase in thermogenin mRNA was nearly completely abolished. It is concluded that the euthyroid state is essential for the regulation of the expression of the thermogenin gene.

Adipose Tissue, Brown↗

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

Catecholamine stimulation of iodothyronine 5'-deiodinase activity in rat dispersed brown adipocytes.

We describe an in vitro system for evaluating the direct effects of catecholamines on the activity of the type II iodothyronine 5'-deiodinase in dispersed rat brown adipocytes. Incubation with norepinephrine or phenylephrine for 3-4 h causes up to a 5-fold increase in deiodinase activity in these cells. As found in vivo studies, the norepinephrine stimulation is blocked by coincubation with the alpha 1-adrenergic antagonist prazosin. The beta-adrenergic antagonist alprenolol either has no effect or increases stimulation by norepinephrine. These results suggest that beta-adrenergic agonists inhibit the activation or synthesis of the deiodinase in these cells.

Adipose Tissue, Brown↗

PubMed1986

The role of 3,3',5'-triiodothyronine in the regulation of type II iodothyronine 5'-deiodinase in the rat cerebral cortex.

Type II iodothyronine 5'-deiodinase (5'D-II) activity is the source of 75-80% of the cerebral cortex T3 content in euthyroid rats. The activity of this enzyme is increased in hypothyroidism and can be quickly suppressed by T4 and rT3 by mechanisms involving neither protein synthesis nor nuclear T3 receptors. We have examined the possibility that endogenous cerebrocortical rT3 levels play a physiological role in the regulation of this enzyme. Thyroidectomized rats were injected with graded doses of [125I]rT3, and cortex 5'D-II activity and rT3 content were determined at various times thereafter. Enzyme activity was reduced as early as 10 min after the injection of 0.75 microgram rT3/100 g BW, and 18 h after 25 micrograms/100 g BW remained 60% suppressed. Regardless of the time after the injection, 5'D-II activity was inversely related to the rT3 content in the cortex; nearly complete suppression was observed at 0.5 ng rT3/g tissue, 50% at 80 pg/g, and 20-30% at 30 pg/g, the euthyroid level. After the infusion of 0.75 microgram rT3/100 g, maximal inhibition occurred at 10 min, before the rT3 content reached maximum levels, and the 5'D-II activity started to recover after the rT3 level fell below 300 pg/g tissue. After increasing doses of T4 administered to thyroidectomized rats, serum and cerebrocortical T4 concentrations increased in a dose-dependent manner, but the increment in the latter was steeper than that in the former. Serum rT3 increments were also proportional to the dose of T4, but cerebrocortical rT3 increased to a greater extent, as evidenced by a 3-fold increment in the cerebrocortical rT3 to T4 ratio. With 1.6 microgram T4/100 g BW, cerebrocortical rT3 reached approximately 100 pg/g, about 3 times the euthyroid level, suggesting that at this T4 dose, the rT3 formed from T4 accounts for part of the inhibition of 5'D-II. With the half-maximal suppressive dose of T4, cortex T4 was about 400 pg/g, but rT3 was negligible. We conclude that: suppression of cortex 5'D-II by rT3 is rapid and requires the presence of rT3 in the tissue (i.e. no long-lived mediators); intracortical rT3 is about 5 times more potent than T4 in suppressing this enzyme; the cortex of rT3-5'D-II suppression relationships suggest that the euthyroid levels of cortex rT3 may be significant in the modulation of 5'D-II.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Plasma kinetics, tissue distribution, and cerebrocortical sources of reverse triiodothyronine in the rat.

Studies in vitro have shown that rT3 is a potent and competitive inhibitor of T4 5'-deiodination (5'D). Recent studies in vivo have shown that cerebrocortical (Cx) T4 5'D-type II (5'D-II) activity [propylthiouracil (PTU) insensitive pathway], is reduced by T4 and rT3, the latter being more potent than T3 in Cx 5'D-II suppression. Some other reports had described rT3 production in rat brain as a very active pathway of thyroid hormone metabolism. To examine the possibility that rT3 plays a physiological role in regulating Cx 5'D-II, we have explored rT3 plasma kinetics, plasma to tissue exchange, and uptake by tissues in the rat, as well as the metabolic routes of degradation and the sources of rT3 in cerebral cortex (Cx). Plasma and tissue levels were assessed with tracer [125I]rT3. Two main compartments were defined by plasma disappearance curves in euthyroid rats (K1 = -6.2 h-1 and K2 = -0.75 h-1). In Cx of euthyroid rats, [125I]rT3 peaked 10 min after iv injection, tissue to plasma ratio being 0.016 +/- 0.004 (SE). In thyroidectomized rats, plasma and tissue [125I]rT3 concentrations were higher than in euthyroid rats, except for the Cx that did not change. PTU caused further increases in all the tissues studied, except for the Cx and the pituitaries of thyroidectomized rats. From the effect of blocking 5'D-I with PTU or reducing its activity by making the animals hypothyroid, we concluded that 5'D-I accounts for most of the rT3 clearance from plasma. In contrast, in Cx and pituitary the levels of rT3 seem largely affected by 5'D-II activity. Since the latter results suggest that plasma rT3 does not play a major role in determining rT3 levels in these tissues, we explored the sources of rT3 in Cx using [125I]T4. The [125I]rT3 (T4) to [125I]T4 ratio remained constant at 0.03 from 1 up to 5 h after injection of [125I]T4. From plasma levels of T4 and rT3, Cx concentration was calculated to be 30 pg rT3/g Cx in euthyroid rats, more than 98% locally produced from T4 deiodination. We conclude that rT3 has a very rapid metabolism, mainly attributed to 5'D-I activity, but that 5'D-II could also play a role in certain tissues. Nearly all rT3 present in Cx is locally derived from T4.

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↗

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↗