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Biomedical subjects

A Campos-Barros

Publications and source records attributed to A Campos-Barros.

At least 19 recordsLinked to original sources
PubMed2005

Protective effects of insulin-like growth factor-I on the somatostatinergic system in the temporal cortex of beta-amyloid-treated rats.

Insulin-like growth factor-I (IGF-I) has protective effects against beta-amyloid (Abeta)-induced neuronal cell death. Because alterations of the somatostatinergic system have been described in Alzheimer's disease, we investigated the effects of the Abeta peptide and the possible protective role of IGF-I on the somatostatinergic system of the rat temporal cortex and on cell death and phosphorylated (p)-Akt levels in this area. Abeta25-35 was administered intracerebroventricularly to male rats via an osmotic minipump over 14 days (300 pmol/day). Another group received a subcutaneous IGF-I infusion (50 microg/kg/day), concomitant with Abeta25-35 administration, whereas a third group received IGF-I alone. Abeta25-35 significantly decreased the somatostatin (SRIF)-like immunoreactive content and the SRIF receptor density, as a result of a decrease in the levels of the SRIF receptor subtype 2. The inhibitory effect of SRIF on adenylyl cyclase activity was significantly lower after Abeta25-35 infusion, whereas the levels of the inhibitory G protein subunit Gialpha1, Gialpha2 or Gialpha3 were unaltered. Cell death was increased and p-Akt levels decreased in Abeta25-35-treated animals. IGF-I administration increased immunoreactive IGF-I levels in the temporal cortex and restored all parameters affected by Abeta25-35 to baseline values. These findings suggest that IGF-I prevents the deleterious effect of Abeta25-35 on the somatostatinergic system.

Alzheimer Disease↗
PubMed2001

Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes.

May-Hegglin anomaly (MHA) and Fechtner (FTNS) and Sebastian (SBS) syndromes are autosomal dominant platelet disorders that share macrothrombocytopenia and characteristic leukocyte inclusions. FTNS has the additional clinical features of nephritis, deafness, and cataracts. Previously, mutations in the nonmuscle myosin heavy chain 9 gene (MYH9), which encodes nonmuscle myosin heavy chain IIA (MYHIIA), were identified in all three disorders. The spectrum of mutations and the genotype-phenotype and structure-function relationships in a large cohort of affected individuals (n=27) has now been examined. Moreover, it is demonstrated that MYH9 mutations also result in two other FTNS-like macrothrombocytopenia syndromes: Epstein syndrome (EPS) and Alport syndrome with macrothrombocytopenia (APSM). In all five disorders, MYH9 mutations were identified in 20/27 (74%) affected individuals. Four mutations, R702C, D1424N, E1841K, and R1933X, were most frequent. R702C and R702H mutations were only associated with FTNS, EPS, or APSM, thus defining a region of MYHIIA critical in the combined pathogenesis of macrothrombocytopenia, nephritis, and deafness. The E1841K, D1424N, and R1933X coiled-coil domain mutations were common to both MHA and FTNS. Haplotype analysis using three novel microsatellite markers revealed that three E1841K carriers--one with MHA and two with FTNS--shared a common haplotype around the MYH9 gene, suggesting a common ancestor. The two new globular-head mutations, K371N and R702H, as well as the recently identified MYH9 mutation, R705H, which results in DFNA17, were modeled on the basis of X-ray crystallographic data. Altogether, our data suggest that MHA, SBS, FTNS, EPS, and APSM comprise a phenotypic spectrum of disorders, all caused by MYH9 mutations. On the basis of our genetic analyses, the name "MYHIIA syndrome" is proposed to encompass all of these disorders.

Amino Acid Sequence↗
PubMed2001

Distinct tissue-specific roles for thyroid hormone receptors beta and alpha1 in regulation of type 1 deiodinase expression.

Type 1 deiodinase (D1) metabolizes different forms of thyroid hormones to control levels of T3, the active ligand for thyroid hormone receptors (TR). The D1 gene is itself T3-inducible and here, the regulation of D1 expression by TRalpha1 and TRbeta, which act as T3-dependent transcription factors, was investigated in receptor-deficient mice. Liver and kidney D1 mRNA and activity levels were reduced in TRbeta(-/-) but not TRalpha1(-/-) mice. Liver D1 remained weakly T3 inducible in TRbeta(-/-) mice whereas induction was abolished in double mutant TRalpha1(-/-)TRbeta(-/-) mice. This indicates that TRbeta is primarily responsible for regulating D1 expression whereas TRalpha1 has only a minor role. In kidney, despite the expression of both TRalpha1 and TRbeta, regulation relied solely on TRbeta, thus revealing a marked tissue restriction in TR isotype utilization. Although TRbeta and TRalpha1 mediate similar functions in vitro, these results demonstrate differential roles in regulating D1 expression in vivo and suggest that tissue-specific factors and structural distinctions between TR isotypes contribute to functional specificity. Remarkably, there was an obligatory requirement for a TR, whether TRbeta or TRalpha1, for any detectable D1 expression in liver. This suggests a novel paradigm of gene regulation in which the TR sets both basal expression and the spectrum of induced states. Physiologically, these findings suggest a critical role for TRbeta in regulating the thyroid hormone status through D1-mediated metabolism.

Animals↗
PubMed2000

Type 2 iodothyronine deiodinase expression in the cochlea before the onset of hearing.

Thyroid hormone signaling during a postnatal period in the mouse is essential for cochlear development and the subsequent onset of hearing. To study the control of this temporal dependency, we investigated the role of iodothyronine deiodinases, which in target tissues convert the prohormone thyroxine into triiodothyronine (T3), the active ligand for the thyroid hormone receptor (TR). Type 2 5'-deiodinase (D2) activity rose dramatically in the mouse cochlea to peak around postnatal day 7 (P7), after which activity declined by P10. This activity peak a few days before the onset of hearing suggests a role for D2 in amplifying local T3 levels at a critical stage of cochlear development. A mouse cochlear D2 cDNA was isolated and demonstrated near identity to rat D2. In situ hybridization localized D2 mRNA in periosteal connective tissue in the modiolus, the cochlear outer capsule and the septal divisions between the turns of the cochlea. Surprisingly, D2 expression in these regions that give rise to the bony labyrinth was complementary to TR expression in the sensory epithelium. Thus, the connective tissue may control deiodination of thyroxine and release of T3 to confer a paracrine-like control of TR activation. These results suggest that temporal and spatial control of ligand availability conferred by D2 provides an unexpectedly important level of regulation of the TR pathways required for cochlear maturation.

Amino Acid Sequence↗
PubMed1999

Novel insight from transgenic mice into thyroid hormone resistance and the regulation of thyrotropin.

Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or TSH) production. The molecular basis of this disorder resides in the dominant inhibition of endogenous thyroid hormone receptors (TRs) by a mutant receptor. To determine the relative contributions of pituitary versus hypothalamic resistance to the dysregulated production of thyroid hormone in these patients, we developed a transgenic mouse model with pituitary-specific expression of a mutant TR (Delta337T). The equivalent mutation in humans is associated with severe generalized RTH. Transgenic mice developed profound pituitary resistance to thyroid hormone, as demonstrated by markedly elevated baseline and non-triodothyronine (T3)-suppressible serum TSH and pituitary TSH-beta mRNA. Serum thyroxine (T4) levels were only marginally elevated in transgenic mice and thyrotropin-releasing hormone (TRH) gene expression in the paraventricular hypothalamus was downregulated. After TRH administration, T4 concentrations increased markedly in transgenic, but not in wild-type mice. Transgenic mice rendered hypothyroid exhibited a TSH response that was only 30% of the response observed in wild-type animals. These findings indicate that pituitary expression of this mutant TR impairs both T3-mediated suppression and T3-independent activation of TSH production in vivo. The discordance between basal TSH and T4 levels and the reversal with TRH administration demonstrates that resistance at the level of both the thyrotroph and the hypothalamic TRH neurons are required to elevate thyroid hormone levels in patients with RTH.

Animals↗
PubMed1999

Thyroid hormone is essential for pituitary somatotropes and lactotropes.

Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH, and FSH activity (alphaGsu-/-) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormone-producing cells of the anterior pituitary are present in alphaGsu-/- mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lactotropes are underrepresented. The size and number of gonadotropes in alphaGsu mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alphaGsu mutants (13-fold relative to wild-type) than in hyt or hpg mutants (4.5- and 1.5-fold, respectively). In addition, T4 replacement therapy of alphaGsu mutants restores lactotropes to near-normal levels, illustrating the importance of T4, but not alpha-subunit, for lactotrope proliferation and function. T4 replacement is permissive for gonadotrope hypertrophy in alphaGsu mutants, consistent with the role for T4 in the function of gonadotropes. This study reveals the importance of thyroid hormone in developing the appropriate proportions of anterior pituitary cell types.

Animals↗
PubMed1997

Effects of lithium and carbamazepine on thyroid hormone metabolism in rat brain.

The effects of lithium (LI) and carbamazepine (CBM) on thyroid hormone metabolism were investigated in 11 regions of the brain and three peripheral tissues in rats decapitated at three different times of day (4:00 A.M., 1:00 P.M., and 8:00 P.M.). Interest was focused on the changes in the two enzymes that catalyze: (1) the 5'deiodination of T4 to the biologically active T3, i.e., type II 5'deiodinase (5'D-II) and (2) the 5 (or inner-ring) deiodination of T3 to the biologically inactive 3'3-T2, i.e., type III 5 deiodinase (5D-III). A 14-day treatment with both LI and CBM induced significant reductions in 5D-III activity. However, 5'D-II activity was elevated by CBM and reduced by LI, both administered in concentrations leading to serum levels comparable with those seen in the prophylactic treatment of affective disorders. The effects were dose dependent, varied according to the region of the brain under investigation, and strongly depended on the time of death within the 24-hour rhythm. The consequences of these complex effects of LI and CBM on deiodinase activities for thyroid hormone function in the CNS and also their possible involvement in the mechanisms underlying the mood-stabilizing effects of both LI and CBM remain to be investigated.

Animals↗
PubMed1997

Evidence for circadian variations of thyroid hormone concentrations and type II 5'-iodothyronine deiodinase activity in the rat central nervous system.

The 24-h patterns of tissue thyroid hormone concentrations and type II 5'- and type III 5-iodothyronine deiodinase (5'D-II and 5D-III, respectively) activities were determined at 4-h intervals in different brain regions of male euthyroid rats entrained to a regular 12-h light/12-h dark cycle (lights on at 6:00 a.m.). Activity of 5'D-II, which catalyzes the intracellular conversion of thyroxine (T4) to 3,3',5-triiodo-L-thyronine (T3) in the CNS, and the tissue concentrations of both T4 and T3 exhibited significant daily variations in all brain regions examined. Periodic regression analysis revealed significant circadian rhythms with amplitudes ranging from 9 to 23% (for T3) and from 15 to 40% (for T4 and 5'D-II) of the daily mean value. 5'D-II activity showed a marked nocturnal increase (1.3-2.1-fold vs. daytime basal value), with a maximum at the end of the dark period and a minimum between noon and 4:00 p.m. 5D-III did not exhibit circadian patterns of variation in any of the brain tissues investigated. Our results disclose circadian rhythms of 5'D-II activity and thyroid hormone concentrations in discrete brain regions of rats entrained to a regular 12:12-h light-dark cycle and reveal that, in the rat CNS, T3 biosynthesis is activated during the dark phase of the photoperiod. For all parameters under investigation, the patterns of variation observed were in part regionally specific, indicating that different regulatory mechanisms may be involved in generating the observed rhythms.

Analysis of Variance↗
PubMed1997

Effects of selenium and iodine deficiency on thyroid hormone concentrations in the central nervous system of the rat.

OBJECTIVE: The effects of single and combined nutritional selenium and iodine deficiency on intracellular thyroid hormone concentrations and type II 5'-iodothyronine deiodinase (5'D-II) activity were examined in different regions of the adult rat brain. DESIGN: Four groups (n = 6) of weanling female Wistar rats proceeding from a breeding line fed a selenium-deficient or a selenium-replete diet for 3 generations, were fed selenium-deficient, iodine-deficient, combined selenium- and iodine-deficient or selenium- and iodine-replete diets for 2 months before they were killed. METHODS: Tissue thyroxine (T4) and tri-iodothyronine (T3) concentrations were determined by highly sensitive RIAs after extraction of the iodothyronines from the tissue samples. The measurement of 5'D-II was based on the release of radioiodide from the 125I-labelled substrate. RESULTS: Selenium deficiency significantly decreased tissue T3 concentrations in the hippocampus, hypothalamus and striatum to 70-80% of controls, whereas no significant changes were found in the cerebellum, cerebral cortex and brain stem. Tissue T4 concentrations were only marginally affected with the exception of a 35% increase in the cerebral cortex. Iodine deficiency dramatically diminished serum T4 levels as well as intracellular T4 concentrations in all regions examined up to 10-30% of control. In spite of a threefold enhancement of 5'D-II, the iodine-deficient animals still had a significant reduction of tissue T3 concentrations (50-65% of controls) in all regions excepting the cerebellum. The combination of selenium and iodine deficiency did not significantly alter this pattern of changes. CONCLUSIONS: These findings suggest that prolonged selenium deficiency as well as iodine deficiency may compromise thyroid hormone homeostasis in the adult brain leading to tissue hypothyroidism and therefore to impaired brain function.

Animals↗
PubMed1996

Serum concentrations of thyroid hormones in patients with nonseasonal affective disorders during treatment with bright and dim light.

Serum concentrations of thyroxine (T4), triiodothyronine (T3), and thyrotropine were measured in 34 patients with nonseasonal affective disorders before and after 1 week of light treatment. Nineteen of these patients received bright white light (2500 lx) and 15 dim red light (50 lx) for 2 hours daily in the mornings over a 1-week period. Slight but significant reductions in the rating scores for the depressive symptomatology were found for both the bright-and dim-light groups, but there were no significant differences between the two groups. The improvement is thus most likely a placebo effect. Surprisingly, the small changes in the severity of the depressive symptoms in the group as a whole were significantly correlated to the changes in the serum levels of T4 during the weeks of bright- and dim-light treatment, respectively. The more a patient improved, the further his or her T4 level fell and vice versa. The fluctuations in the concentrations of T4 during light treatment were significantly greater in the depressed patients than in a group of 12 healthy controls who also received bright or dim light, whereas the changes in T3 were significantly smaller than those of the healthy controls. The pronounced fluctuations in T4 levels were probably not secondary to changes in mood. Rather, they are likely to reflect changes in tissue (intracellular) metabolism of T4, which may be involved in the mechanisms underlying the fluctuations in mood in these patients.

Adult↗
PubMed1996

Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system.

In the present study we investigated the biochemical properties of in vitro phenolic (5'D) and tyrosyl (5D) ring deiodination and the tissue concentrations of T4, T3, and rT3 in adult human central nervous system (CNS) tissue. All samples were obtained from nontumoral tissue at autopsy (n = 6) or neurosurgical operation (n = 5). Both phenolic and tyrosyl ring deiodinase activities were demonstrable in all samples obtained intraoperatively, whereas only tyrosyl ring deiodination was evident in the tissues obtained postmortem. The phenolic ring deiodination pathway corresponded to the type II 5'-deiodinase isoenzyme with regard to its high affinity for T4 and rT3 (Km = 2.2 and 2.4 nmol/L, respectively), its insensitivity to 6-propyl-n-2-thiouracil (PTU), and the sequential reaction mechanism. No PTU-sensitive 5'-deiodination of rT3 was demonstrable. Tyrosyl ring deiodination of both T4 and T3 showed typical type III 5D kinetics (Ka, 6.5 nmol/L for T4 and 3.4 nmol/L for T3) and was PTU insensitive. Nanomolar concentrations of tissue T4, T3, and rT3 were detected in samples obtained both intraoperatively and postmortem. They were very similar to the absolute values of the apparent Km for T4, T3, and rT3 in the phenolic and tyrosyl ring deiodination pathways. In conclusion, we have demonstrated the coexistence of both phenolic and tyrosyl ring deiodinase activities in the human CNS. Their kinetic characteristics, substrate specificity, and reaction mechanisms are very similar to the corresponding type II 5'- and type III 5-iodothyronine deiodinase activities in rat brain. In contrast to the findings in the rat CNS, no PTU-sensitive phenolic ring deiodinase (i.e. type I 5'D) activity was found in the human CNS. This may explain the relatively high tissue concentrations of rT3.

Adolescent↗
PubMed1995

The effects of desipramine on thyroid hormone concentrations in rat brain.

The effects of the antidepressant desipramine on the tissue concentrations of thyroxine and triiodothyronine in 9 different regions of the brain and also in the pituitary and liver were investigated in male rats. The investigations were carried out at three different times of the light/dark cycle: 5 a.m., 1 p.m. and 11 p.m. After fourteen days' treatment with 20 mg/kg/day desipramine by gavage the concentrations of triiodothyronine in the frontal and parieto-occipital cortex were significantly higher than in the saline-treated controls, those in the hippocampus lower and those in the 6 remaining brain regions the same. In 8 areas of the brain the concentrations of thyroxine were lower in the desipramine-treated rats and the tissue ratios of triiodothyronine to thyroxine were enhanced in 6 regions. These effects are most likely the result of the action of desipramine on the activity of the isoenzyme 5'II deiodinase. This enzyme catalyzes the deiodination of thyroxine to triiodothyronine in rat brain and its activity has recently been reported to be enhanced by desipramine. The observed effects were dose-dependent and also strongly dependent upon the time within the 24 h light/dark cycle at which the hormone concentrations were measured. No effects of desipramine were seen in the pituitary or liver after 14 days' treatment, or in various areas of the central nervous system 24 h after administration. In view of the psychotropic properties of thyroid hormones, it seems possible that the observed increases in triiodothyronine concentrations, particularly in cortical areas, are involved in the mechanisms of action of desipramine.

Administration, Oral↗
PubMed1994

Subchronic administration of fluoxetine to rats affects triiodothyronine production and deiodination in regions of the cortex and in the limbic forebrain.

The effects of subchronic administration of the antidepressant fluoxetine (15 mg/kg i.p., 14 days) on thyroid hormone metabolism were investigated in 11 regions of the CNS and three peripheral tissues in the rat. Fluoxetine significantly enhanced the activity of the 5'II-deiodinase isoenzyme (5'D-II), which catalyzes the deiodination of the inactive prohormone thyroxine (T4) to the active compound triiodothyronine (T3) in areas of the cortex, the limbic forebrain and the striatum. The activity of the 5D-III deiodinase isoenzyme (5D-III), which catalyzes the further deiodination of T3 to the inactive metabolite 3,3'-T2, was inhibited in the first two of these areas. The areas affected were roughly the same as those with the highest density of 5-HT2 receptors in rat brain. Theoretically, the enhancement 5'D-II activity, together with a concomitant decrease in 5D-III activity, should lead to a rise in T3 concentrations. Whether or not these effects are involved in the as yet unknown mechanism of action of this antidepressant compound is discussed.

Animals↗
PubMed1994

Carbamazepine affects triiodothyronine production and metabolization in rat hippocampus.

The effects of subchronic administration of carbamazepine on thyroid hormone metabolism were investigated in the hippocampus in adult male rats at two different measuring times (4 a.m. and 8 p.m.). Carbamazepine enhanced the activity of 5'II-deiodinase, which catalyzes the deiodination of the prohormone T4 to the active compound T3, at 8 p.m., but not at 4 a.m. The activity of 5III-deiodinase, which catalyzes the further deiodination of the active hormone T3 to its metabolite 3,3'T2, was inhibited at 4 a.m. but not at 8 p.m. These effects of carbamazepine on intracellular thyroid hormone metabolism in the hippocampus should theoretically lead to a rise in T3 production. It remains to be investigated whether they are somehow involved in the as yet unknown mechanisms underlying the anticonvulsant/mood-stabilizing effects of carbamazepine.

Animals↗
PubMed1994

Hypothalamic-pituitary-thyroid (HPT) axis in chronic alcoholism. I. HPT axis in chronic alcoholics during withdrawal and after 3 weeks of abstinence.

Thyroxine (T4), free T4 (fT4), triiodothyronine (T3), free T3 (fT3), reverse T3 (rT3), thyrotropin (TSH), thyroxine binding globulin (TBG), and T3 uptake were measured in 14 chronic alcoholics during withdrawal and after 21 days of abstinence. Results were compared with those of 16 healthy volunteers. During withdrawal, the fT4 and fT3 concentrations were subnormal, whereas the respective protein-bound fractions were normal. T4, T3, and TBG increased during the abstinence period, T3 and TBG being significantly higher than in normals at the second measuring time. T3 uptake values fell, but remained well within the normal range at both measuring times. During abstinence, the fT3 levels remained significantly lower than in healthy subjects. rT3 concentrations decreased, but not significantly. The TSH values were normal throughout. These results showed numerous abnormalities in the hypothalamic-pituitary-thyroid axis in alcoholics, the reasons for which are as yet unclear. The following possible interpretations are suggested: 1. The abnormally low serum fT3 and fT4 levels during withdrawal might reflect an increase in tissue uptake. 2. The increases in T4--and partly those in T3--during abstinence seem to reflect increased binding by TBG, the level of which rose markedly for reasons as yet unknown. 3. If increases in TBG during abstinence are taken into account, the decreases in rT3 concentrations may reach the level of statistical significance. These falls in rT3 concentrations may reflect an increase in rT3 metabolization (deiodination) in various tissues, including the CNS, leading to a reduction in serum rT3 bioavailability. 4. Factors such as liver disease, protein caloric malnutrition, and "psychological stress" do not fully explain all these abnormalities. A direct effect of ethanol on intracellular thyroid hormone metabolism and/or function seems conceivable.

Adult↗
PubMed1994

Hypothalamic-pituitary-thyroid axis in chronic alcoholism. II. Deiodinase activities and thyroid hormone concentrations in brain and peripheral tissues of rats chronically exposed to ethanol.

Thyroxine (T4), triiodothyronine (T3) concentrations, and the activities of the three deiodinase isoenzymes were measured in different brain regions and peripheral tissues of rats. According to an animal model of alcohol addiction, "behaviorally" dependent rats having lost control over their intake of ethanol were compared with alcohol-naive controls and ethanol-experienced, but "controlled" consumers. The two kinds of alcohol-experienced rats were investigated either 24 hr or 3 months after ethanol withdrawal. The results of these four groups were compared with those of an ethanol-naive control group. During withdrawal, the activities of type II 5'-deiodinase (which catalyzes deiodination of T4 and T3 in the CNS) in both the "behaviorally dependent" rats and the "controlled drinkers" were significantly lower than in the alcohol-naive controls in the frontal cortex, parieto-occipital cortex, hippocampus, and striatum, but not in the cerebellum or pituitary. Probably as a result, the tissue concentrations of T4 were higher in areas of the CNS in the groups exposed to alcohol. However, the T3 concentrations were normal. No relevant differences were seen between the activities of type III 5-deiodinase (which catalyzes the further deiodination of T3) observed in these groups. After 3 months of abstinence, the type II 5'-deiodinase activities had almost returned to normal in both "controlled drinkers" and "behaviorally dependent" animals, whereas type III 5-deiodinase activity was inhibited, possibly to maintain physiological concentrations of T3 during abstinence. Indeed, the tissue levels of T3 were normal in the areas of the CNS, and the T4 levels were still elevated. However, the liver concentrations of T3 and T4 were significantly lower in the "behaviourally dependent" animals than in the "controlled" drinkers after 3 months of abstinence, whereas no differences were found between the T4 and T3 concentrations in the areas of the CNS investigated in the two groups exposed to ethanol. These results suggest that chronic administration of ethanol affects intracellular thyroid hormone metabolism in both rat CNS and liver in the highly complex manner. No direct evidence of ethanol-induced enhancement of tissue uptake or concentrations was obtained. However, taking into account the numerous similarities between the clinical picture of hyperthyroidism and the symptomatology of alcoholism, it may be hypothesized that ethanol may directly influence any step in the as yet unknown biochemical cascade of thyroid hormone function.

Alcoholism↗