Reduction In T4 Research Articles

Avaliação dos níveis séricos de hormônios tireóideos em revascularização miocárdica

JUSTIFICATIVAS E OBJETIVOS: Os hormônios tireóideos tiroxina (T4) e triiodotironina (T3) regulam o anabolismo de proteínas, lipídios e carboidratos e aumentam o consumo de oxigênio. Estresse cirúrgico e circulação extracorpórea (CEC) podem alterar os níveis hormonais ativos por meio de interferência na conversão periférica e diminuição do nível sérico de T3 sem alterações da tirotrofina (TSH), caracterizando a síndrome eutireóidea. Objetivou-se comparar os níveis séricos de T3, T4 e TSH em pacientes submetidos à revascularização miocárdica (RM) com ou sem utilização de CEC. MÉTODO: Foram estudados 18 pacientes com programação para cirurgia eletiva de RM, sendo: Grupo CEC (n = 9): pacientes submetidos à CEC e Grupo sem CEC (n = 9): pacientes não submetidos à CEC. Realizou-se dosagem de T3, T4 e TSH séricos antes da indução anestésica (início SO), ao término da cirurgia (final SO), no primeiro dia (1º PO) e no segundo dia de pós-operatório (2º PO). Na análise estatística (Análise de Variância de medidas repetidas, teste de Mann-Whitney e prova de Friedman) considerou-se significativo p < 0,05. RESULTADOS: Ocorreu diminuição do nível sérico de T3 nos dois grupos. Os níveis séricos de T4 mostraram diferença entre os momentos final SO e 1º PO, quando o grupo não-submetido à CEC mostrou níveis mais elevados de T4. Os níveis séricos de TSH permaneceram dentro dos limites da normalidade. CONCLUSÕES: Ocorre diminuição dos níveis séricos de T3 após revascularização miocárdica com e sem a utilização de CEC e com maior diminuição de T4 no grupo submetido à CEC. A ausência de resposta hipofisária às alterações dos níveis séricos de T3 e T4 caracteriza a síndrome eutireóidea nos dois grupos.

Developmental exposure to low-dose PBDE-99: Tissue distribution and thyroid hormone levels

Thyroid hormone concentrations, hepatic enzyme activities and tissue concentrations of 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) were evaluated in Wistar rats (dams and offspring) after treatment by gavage on gestation day (GD) 6 with a single low dose of either 60 or 300 μg PBDE-99/kg body weight (bw), respectively. Tissue concentration analysis confirmed that PBDE-99 is persistent in rodents as significant amounts of the parent compound were detected in adipose tissue 37 days after exposure. The dose of 300 μg PBDE-99/kg bw reduced thyroxin (T4) concentration in dams at the beginning of lactation (post-gestational day [PGD] 1), and caused a slight reduction in T4 on PGD 22, although not statistically significant. In offspring, reduced T4 was observed only at PND 22, probably due to cumulative effects of PBDE-99 during lactation. PBDEs have been shown to reduce T4 concentrations in several studies, but this is the first study demonstrating endocrine disruption at low doses. The adipose tissue concentration of PBDE-99 measured in this study was close to those reported for PBDE-99 in non-occupationally exposed humans. In addition, we have previously reported permanent changes in the reproductive systems and locomotor activity of male and female offspring using these same dosages.

Prenatal PCB and PBDE Exposure and Thyroid Hormones

ISEE-663 Objective: Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are organohalogen chemicals that have been applied commercially to insulate and reduce product flammability. Studies examining the health effects of PCBs and PBDEs have focused on their propensity to disrupt the endocrine system, in part because of their structural and functional similarity to the thyroid hormone, thyroxine (T4). This study was designed to investigate the relationship between prenatal exposure to PCBs and PBDEs and thyroid hormone levels in newborns. Materials and Methods: Prenatal exposure to PCBs and PBDEs was estimated from levels measured in umbilical cord blood collected from women delivering at the Johns Hopkins Hospital. Thyrotropin (TSH) and total and free T4 were measured in cord serum and total T4 was also assessed in newborn blood spots. Demographic and biological measures, including medical history, were abstracted from maternal medical records. Results: After adjustment for relevant confounders, we found that none of the compounds we studied showed a positive association with higher TSH levels, as hypothesized. There appeared to be no observable relationship between free T4 and PCB and PBDE levels in the overall population. Higher levels of all PCBs, BDE-100, and BDE-153 tended to be associated with lower total T4 levels in cord blood; for total T4 in blood spots; however, the trend between PCBs and T4 was positive. We found evidence of effect modification, such that associations between PCBs and PBDEs and cord total T4 and associations between PCBs and free T4 were stronger when restricted to spontaneous unassisted vaginal deliveries. Conclusions: Although the results observed are not consistent with reported relationships between PCBs, PBDEs, and thyroid hormones in animal models, there is evidence for thyroid perturbations involving a reduction in T4 without a commensurate increase in TSH production associated primarily with PCB but also with selective PBDE congeners.

Thyroid Function in Patients With Alzheimer Disease: Implications on Response to Anticholinesterase Treatment

Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in Alzheimer disease (AD). The aim of the present study was to explore thyroid function in patients with AD before and after acetylcholinesterase inhibition treatment to possibly identify variances in response. Thyroid function tests were evaluated in 28 AD patients and 24 age and sex-matched controls. Nineteen of the patients were reevaluated after (4 mo) treatment with donepezil. Serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), the free fractions (fT3, fT4) and thyroid autoantibodies were determined using standard methods. All subjects were clinically euthyroid. Patients presented with higher fT4 and anti-thyroperoxidase levels, as compared with the controls. Significant reduction in T4, fT3, fT4, and anti-thyroperoxidase levels were observed 4 months after treatment. Responders had higher T4 and fT4, than nonresponders, followed by significant reductions after treatment. The above, within the normal range alterations, may represent a direct effect on hormone release from the thyroid gland and/or increased conversion of T4 to T3 within the brain. Higher T4 and fT4 levels before treatment might predict a favorable response to donepezil treatment.

Dopamine Infusion and Anterior Pituitary Gland Function in Very Low Birth Weight Infants

Background: Previous studies demonstrated that dopamine infusion reduces plasma concentration of thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) in adults, children, and infants. Objectives: The purpose of this prospective observational study was to evaluate the relationship between dopamine infusion and the dynamics of T4, TSH, PRL, and GH in preterm newborns weighing less than 1,500 g (very low birth weight infants, VLBW) admitted in a neonatal intensive care unit of a university hospital over a one year period. Methods: A total of 97 preterm newborns were enrolled and divided into two groups: group B included hypotensive infants treated with plasma expanders and dopamine infusion; group A was the control group including newborns who were never treated with dopamine. The newborns were studied dynamically through blood samples taken every day till 10 days. Newborns of group B were studied during dopamine infusion and after its withdrawal. Results: Among the VLBW newborns who were given dopamine, the four pituitary hormones had different dynamics: a reduction of T4, TSH, and PRL levels was noticed since the first day of treatment, and a rebound of their levels was evident since the first day after its interruption. On the contrary, the postprandial GH levels were roughly constant: GH plasma concentrations were in fact a little lower in newborns treated with dopamine, and a slight increase was observed after its withdrawal. However, observed differences were not statistically significant. Conclusions: The results suggest that dopamine infusion reduces T4, TSH, and PRL plasma levels in preterm VLBW infants and have no effect on postprandial GH rate. This hormonal suppression reverses rapidly after dopamine withdrawal. This observation suggests that the iatrogenic pituitary suppression probably cannot produce long-term injuries.

Body mass, spleen mass and level of thyroid hormones in juvenile hypothyroid rats

In this paper, the effect of hypothyroidism on body mass and spleen mass of rats was examined during the prenatal and early juvenile periods. Hypothyroidism was induced by the application of propylthiouracil (PTU) in drinking water to the mothers from the first day of gravidity and during lactation, and the offspring were sacrificed on the 14th and 21st days after birth. The body mass of the juvenile rats was measured just before they were sacrificed. The concentrations of triiodothyronine (T3) and thyroxine (T4) in blood serum were determined in control and treated juvenile rats. The results indicate that PTU leads to a reduction in T3 and T4 serum concentrations in treated juvenile rats. Treated juvenile rats had a bigger body mass and spleen mass in comparison with control animals. These data indicate that hypothyroidism induced in the prenatal and early juvenile period leads to an increase in the body mass and spleen mass and disrupts the normal development of the spleen in the course of the examined period. .

Serum Thyroid Hormones in Preterm Infants: Associations with Postnatal Illnesses and Drug Usage

Transient hypothyroxinemia is common in infants less than 30 wk gestation and is associated with neurodevelopmental deficits. Reductions in T4 and T3 levels with TSH unchanged are the key features of severe illness using surrogate indices of overall severity of illness, but these do not inform the impact of individual disease conditions or drug use. Our objective was to investigate the contribution of postnatal factors to the variations in serum levels of iodothyronines, thyroid-binding globulin, and TSH. We recruited a cohort of infants (23-34 wk gestation; n = 780) between January 1998 and September 2001. The study involved 11 level III Scottish neonatal intensive care units and included cohorts of infants delivered at 23-34 wk gestation. We assessed serum levels of iodothyronines, thyroid-binding globulin, and TSH at 7, 14, and 28 d adjusted for the potentially significant postnatal influences (n = 31). Serum levels of TSH, free T4, T3, and T4 are variably but significantly associated with bacteremia, endotracheal bacterial cultures, persistent ductus arteriosus, necrotizing enterocolitis, cerebral ultrasonography changes, oxygen dependence at 28 d, and the use of aminophylline, caffeine, dexamethasone, diamorphine, and dopamine. There are many more associations of postnatal factors with transient hypothyroxinemia than had previously been considered in preterm infants. Alternative strategies should be considered for correction of hypothyroxinemia rather than sole reliance on the direct therapy of hormone replacement. A more oblique preventative approach may be necessary through reduction in the incidence or severity of individual illness(es). Similarly, alternatives to those drugs that interfere with the hypothalamic-pituitary-thyroid axis should be evaluated (e.g. other inotropics instead of dopamine).

Rearrangements in Thyroid Hormone Receptor Charge Clusters That StabilizeBound 3,5′,5-Triiodo-L-thyronine and Inhibit HomodimerFormation

In this study, we investigated how thyroid hormone (3,5',5-triiodo-l-thyronine, T3) inhibits binding of thyroid hormone receptor (TR) homodimers, but not TR-retinoid X receptor heterodimers, to thyroid hormone response elements. Specifically we asked why a small subset of TRbeta mutations that arise in resistance to thyroid hormone syndrome inhibit both T3 binding and formation of TRbeta homodimers on thyroid hormone response elements. We reasoned that these mutations may affect structural elements involved in the coupling of T3 binding to inhibition of TR DNA binding activity. Analysis of TR x-ray structures revealed that each of these resistance to thyroid hormone syndrome mutations affects a cluster of charged amino acids with potential for ionic bond formation between oppositely charged partners. Two clusters (1 and 2) are adjacent to the dimer surface at the junction of helices 10 and 11. Targeted mutagenesis of residues in Cluster 1 (Arg338, Lys342, Asp351, and Asp355) and Cluster 2 (Arg429, Arg383, and Glu311) confirmed that the clusters are required for stable T3 binding and for optimal TR homodimer formation on DNA but also revealed that different arrangements of charged residues are needed for these effects. We propose that the charge clusters are homodimer-specific extensions of the dimer surface and further that T3 binding promotes specific rearrangements of these surfaces that simultaneously block homodimer formation on DNA and stabilize the bound hormone. Our data yield insight into the way that T3 regulates TR DNA binding activity and also highlight hitherto unsuspected T3-dependent conformational changes in the receptor ligand binding domain.

Enhanced reduction and determination of trace thyroxine at carbon paste electrode in the presence of trace cetyltrimethylammonium bromide.

The electrochemical response of thyroxine (T4) at a carbon paste electrode (CPE) in the presence of cetyltrimethylammonium bromide (CTAB) was investigated. It gave a well-defined oxidation peak at 0.80 V and a sensitive reduction peak at 0.40 V. Compared with the indiscernible signal in the absence of CTAB, the reduction current of T4 at CPE was greatly enhanced in the presence of CTAB, due to the interactions between T4, CTAB and the hydrophobic electrode surface. The electrode process of T4 was explored by cyclic voltammetry and chronocoulometry. The effect of surfactants on the reduction reaction proved that bromide ions (Br(-)) in CTAB might form special ion complexes with T4 via a special interaction with the iodine atoms on T4, which would activate the reduction of T4. The sensitive and selective reduction of T4 in this system was applied to the determination of T4 in drugs; a detection limit of 6.5 x 10(-9) M was obtained (sigma= 3).

Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations.

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.

Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study.

The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.

Effects of chronic mild stress on lymphocyte proliferative response. Participation of serum thyroid hormones and corticosterone

There is increasing evidence that stress produces changes in various immune processes. Some of these changes may be due to neurochemical and hormonal alterations including thyroid hormones levels. This work was carried out to study the impact of chronic mild stress (CMS) exposure on proliferative responses and its correlation with serum thyroid hormone levels. In addition, the influence of serum corticosterone levels on these responses was also studied. For this purpose, mice were submitted from 1 to 6 weeks to a CMS model. After undergoing the stress schedule for 4 weeks, an alteration in the proliferative response was observed. Lymphocytes from exposed animals showed a decrease in T-cell response to concanavalin-A (Con A) and phytohemagglutinin (PHA) and an increase in B-cell proliferation to lipopolysaccharides (LPS). In parallel, a reduction in T3 and T4 serum levels was observed. On the contrary, serum corticosterone levels increased in animals exposed to CMS for 1 or 2 weeks and then return to normal values. Lowering serum thyroid hormone levels by propylthiouracil (PTU) treatment negatively modulates T-cell response without affecting B-cell response. On the other hand, the substitutive T4 treatment in stressed animals improved significantly the proliferative T-cell response. Non-significative changes in CD4/CD8 ratio were observed neither in stressed, PTU- or T4-treated animals. Taken together, our results suggest an impact of chronic stress on thyroid function that in turn alters T-cell response. These findings may help to elucidate the physiological mechanisms through which stress plays a roll in the etiology of many diseases.

Thyroid function in patients with chronic renal failure

Chronic renal failure affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands. Both plasma triiodothyronine (T3) and thyroxine (T4) are reduced. The low serum T3 is not due to increased T3 degradation or to decreased thyroidal T3 secretion but is a result of impaired extrathyroidal T4 to T3 conversion. The reduction in T4 is attributed to the presence of circulating inhibitors, which impair binding of T4 to thyroxine-binding globulin. Despite decreased circulating T4 and T3, thyroid-stimulating hormone (TSH) is not elevated. This absence of TSH elevation is not due to dysfunction of the hypothalamo-pituitary axis, because truly hypothyroid renal failure patients can mount a high TSH response. Thyroid hormone losses during hemodialysis and peritoneal dialysis are trivial and do not require replacement. Serum inorganic iodide and thyroidal iodine content are increased in renal failure patients, and thyroid gland enlargement is frequently encountered. Experiments performed to correct the low serum T3 level by administration of small doses of LT3 to renal failure patients resulted in lesser nitrogen balance, greater leucine flux, and protein degradation. We speculate that the low thyroid state in uremia serves to defend against protein wasting and that misguided attempts to replete thyroid hormone stores may worsen protein malnutrition. © 2001 by the National Kidney Foundation, Inc.

Induction of low-T3 syndrome in exercising women occurs at a threshold of energy availability

To investigate the relationship between energy availability (dietary energy intake minus energy expended during exercise) and thyroid metabolism, we studied 27 untrained, regularly menstruating women who performed approximately 30 kcal.kg lean body mass (LBM)-1.day-1 of supervised ergometer exercise at 70% of aerobic capacity for 4 days in the early follicular phase. A clinical dietary product was used to set energy availability in four groups (10.8, 19.0, 25.0, 40.4 kcal.kg LBM-1.day-1). For 9 days beginning 3 days before treatments, blood was sampled once daily at 8 A.M. Initially, thyroxine (T4) and free T4 (fT4), 3,5,3'-triiodothyronine (T3) and free T3 (fT3), and reverse T3 (rT3) were in the normal range for all subjects. Repeated-measures one-way analysis of variance followed by one-sided, two-sample post hoc Fischer's least significant difference tests of changes by treatment day 4 revealed that reductions in T3 (16%, P < 0.00001) and fT3 (9%, P < 0.01) occurred abruptly between 19.0 and 25.0 kcal.kg LBM-1.day-1 and that increases in fT4 (11%, P < 0.05) and rT3 (22%, P < 0.01) occurred abruptly between 10.8 and 19.0 kcal.kg LBM-1.day-1. Changes in T4 could not be distinguished. If energy deficiency suppresses reproductive as well as thyroid function, athletic amenorrhea might be prevented or reversed by increasing energy availability through dietary reform to 25 kcal.kg LBM-1.day-1, without moderating the exercise regimen.

Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes.

The impact of chronic high volume athletic training on thyroid hormone economy has not been defined. We investigated the status of the hypothalamic-pituitary-thyroid axis (H-P-T) in women athletes with regular menstrual cycles (CA) and with amenorrhea (AA). Their data were compared with each other and with those derived from cyclic sedentary women (CS) matched for a variety of confounding factors including the intensity of exercise, caloric intake, and body weight. Alterations of the H-P-T axis were observed in women athletes compared to CS. While serum levels of T4, T3, free T4, free T3 and rT3 were substantially reduced (P less than 0.01) in AA, only serum T4 levels were significantly decreased in CA. Further, remarkable differences were found between CA and AA in that serum levels of free T4 (P less than 0.01), free T3 (P less than 0.01), and rT3 (P less than 0.05) were significantly lower in AA than in CA. Thyroid binding globulin and sex-hormone binding globulin concentrations were within their normal ranges for all groups of subjects. Both 24-h mean TSH levels and the circadian rhythm of TSH secretion were also comparable. However, the TSH response to TRH stimulation was blunted (P less than 0.01) in AA when compared to CA, but not to CS. Whereas the underlying mechanism(s) to account for the "global" reduction of circulating thyroid hormone in the face of normal TSH levels in AA is presently unknown, these observations provide information of clinical significance: 1) chronic high volume athletic training in women athletes with menstrual cyclicity is accompanied by an isolated T4 reduction; 2) an impaired H-P-T axis occurs selectively in athletic women in whom chronic high volume athletic training is associated with compromised hypothalamic-pituitary-ovarian function and amenorrhea.

Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia.

To evaluate the interaction between plasma levels and the systemic uptake of atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group 2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4) supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx + ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2; expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/- 58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/- 6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr, 283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5); however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P less than 0.01). Tx by itself did not change either parameter. The filtering kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/- 8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF. T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a persistently high ANF (145.7 +/- 21). Blood volume did not change in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonal changes in thyroid-gonadal interactions in the edible dormouse, Glis glis.

This study was conducted to determine changes in thyroid-gonadal interaction in the edible dormouse during the phase of the annual cycle that corresponds to the end of the breeding season (from June to September). We evaluated intra-hypothalamic luteinizing hormone-releasing hormone (LHRH) content, and plasma concentrations of luteinizing hormone (LH), testosterone, thyroid-stimulating hormone (TSH) and thyroxine (T4) in three groups of dormice: (1) controls; (2) dormice receiving sufficient T4 supplementation to maintain June levels in control animals until September, thus counteracting the seasonal reduction of T4 that normally begins in July; and (3) thyroidectomized dormice. The effect of thyroidectomy was only detectable in June, when plasma T4 concentration in the control group was maximal, and consisted of a significant decrease in plasma testosterone levels. This provides strong support for the hypothesis that thyroid function positively influences gondal function during the breeding season. The T4 supplementation resulted in a decrease in hypothalamic LHRH concentration, suggesting that an increased LHRH release led to the observed stimulated hypophyseal secretion of LH in June and September and the increased circulating testosterone levels in September. There was no detectable effect in July and August. These results show that thyroid axis activation of the hypothalamic-pituitary-gondal system is only possible during certain phases of the annual cycle, particularly evidenced here during the breeding season. They also reinforce our conclusions drawn from the thyroidectomy results. Conversely, the summer testicular regression which normally occurs after the breeding season is no longer controlled by plasma T4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy.

Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HT through the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with p-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HT turnover.

Cholecystokinin and vasoactive intestinal peptide in brain and gut of the hypothyroid neonatal rat.

The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidenced by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Triiodothyronine, thyroxine, and tsh response to dexamethasone in depressed patients and normal controls

In view of recent investigations concerning alterations of thyroid function in depression, thepre- and postdexamethasone levels of T3, T4, and TSH of 14 patients during depression and after recovery were studied, in addition to those of 27 healthy controls. A reduction of T3 and TSH levels was shown to be dependent on the depressive state, with a tendency to lower T4 levels after recovery. Dexamethasone had a pronounced suppressive effect on TSH levels in healthy controls and in patients after recovery, but not during the depressive episode. These results point to an inadequate suppressibility of the hypothalamo-pituitary-thyroid (HPT) axis to dexamethasone during depression. There are close interrelations between the hypothalamo-pituitary-adrenal (HPA) and the HPT axes that are possibly affected during depressive illness.