Microarray Analysis of Thyroid Stimulating Hormone, Insulin-Like Growth Factor-1, and Insulin-Induced Gene Expression in FRTL-5 Thyroid Cells

To determine which genes are regulated by thyroid stimulating hormone (thyrotropin, TSH), insulin and insulin-like growth factor-1 (IGF-1) in the rat thyroid, we used the microarray technology and observed the changes in gene expression. The expressions of genes for bone morphogenetic protein 6, the glucagon receptor, and cyclin D1 were increased by both TSH and IGF-1; for cytochrome P450, 2c37, the expression was decreased by both. Genes for cholecystokinin, glucuronidase, beta, demethyl-Q 7, and cytochrome c oxidase, subunit VIIIa, were up-regulated; the genes for ribosomal protein L37 and ribosomal protein L4 were down-regulated by TSH and insulin. However, there was no gene observed to be regulated by all three: TSH, IGF-1, and insulin molecules studied. These findings suggest that TSH, IGF-1, and insulin stimulate different signal pathways, which can interact with one another to regulate the proliferation of thyrocytes, and thereby provide additional influence on the process of cellular proliferation.

Changes in some hormones by low doses of di (2-ethyl hexyl) phthalate (DEHP), a commonly used plasticizer in PVC blood storage bags & medical tubing.

BACKGROUND & OBJECTIVES: Di (2-ethyl hexyl) phthalate (DEHP), a plasticizer commonly used in PVC blood storage bags leaches out in significant amounts into blood during storage. In view of many reports on the toxicity of this compound, it was considered necessary to investigate the effect of DEHP at the low level solubilized in blood on some important hormones in rats and in human blood stored in DEHP plasticized blood bags. METHODS: Rats were administered DEHP at a low level of 750 microg/100 g body weight on alternate days for 14 days. Changes in the serum insulin, blood glucose, liver glycogen level and T3, T4 and thyroid stimulating hormone (TSH) as well as cortisol in the serum were studied. Changes in the hormones were also studied in blood stored in DEHP plasticized PVC bags. RESULTS: The results indicated decrease in serum insulin, cortisol and liver glycogen, and increase in blood glucose, serum T3 and T4 in rats receiving DEHP. These changes were reversed when administration of DEHP was stopped. Similar changes in hormones were also observed in the blood stored in DEHP plasticized blood bags. INTERPRETATION & CONCLUSION: The results indicated that administration of DEHP at low levels to rats caused symptoms of diabetes, thyroid and adrenocortical dysfunction. Though the results obtained in rats cannnot be extrapolated to human, the fact that similar hormonal changes seen in human blood stored in DEHP plasticized blood bags may suggest possibility of DEHP causing similar changes in human. The fact that these changes were reversed in rats when DEHP administration was stopped, indicates that transfusion of a few units of blood to a recipient may not be harmful, but it may pose a problem during repeated transfusions such as in thalassaemia patients.

Regulação da síntese e secreção de tireotrofina / Regulation of thyrotropin synthesis and secretion

A secreção de tireotrofina (TSH) é determinada pelo efeito estimulatório do hormônio hipotalâmico estimulador de tireotrofina (TRH) e pela retroalimentação negativa exercida pelos hormônios tireóideos (HT). Superpostos, atuam outros reguladores e aferências do sistema nervoso central. Somatostatina e dopamina inibem a secreção de TSH, já as vias alfa-adrenérgicas centrais são predominantemente estimuladoras e participariam no estímulo da secreção de TSH pelo frio. O estado nutricional modula o eixo através da leptina, por vias diretas e indiretas. O estresse induz redução da secreção de TSH, e discute-se a participação dos glicocorticóides, citocinas e opiáceos. Recentemente, evidenciou-se que fatores locais produzidos na adenohipófise podem atuar de forma autócrina/parácrina, modulando a secreção de TSH. Dentre estes, destacam-se a neuromedina B e o peptídeo liberador de gastrina, que atuam como inibidores locais da secreção de TSH. Discute-se ainda, as alterações do TSH decorrentes da programação neonatal, por hormônios ou desnutrição.

Significance of thyrotrophin and thyroxine estimations in type 1 diabetes

OBJECTIVE: To investigate whether estimation of thyrotrophin [TSH] and thyroxine [T4] is significant to assess the thyroid status of diabetic patients. MATERIALS AND METHODS: Fifty patients with type 1 diabetes [25 male and 25 female] aged 9-50 years were included. The mean duration of diabetes was 6.7 +/- 4.3 years. Clinically they were not suffering from any systemic disease or endocrine ailment. Twenty-six, age and sex matched, normal controls were also included. The TSH and and T4 were estimated in the sera of all the subjects using the commercially available ELISA kits. The mean +/- SD concentration of TSH was raised significantly [p < 0.001] in the patients as compared to the controls, whereas the T4 concentration was comparable. Furthermore, 30% diabetics showed significantly elevated TSH concentration than the controls. It is proposed that the estimation of TSH in the patients with type 1 diabetes may be useful in the early identification of thyroid dysfunction

Thyroid function in post-weaning rats whose dams were fed a low-protein diet during suckling

This study was designed to evaluate the thyroid and pituitary hormone levels in post-weaning rats whose dams were fed a low-protein diet during suckling (21 days). The dams and pups were divided into 2 groups:a control group fed a diet containing 22 per cent protein that supplies the necessary amount of protein for the rat and is the usual content of protein in most commercial rat chow, and a diet group fed a lowprotein (8 per cent) diet in which the protein was substituted by an isocaloric amount of starch. After weaning all dams and pups received the 22 per cent protein diet. Two hours before sacrifice of pups aged 21, 30 and 60 days, a tracer dose (0.6 mui) ofl25I was injected (ip) into each animal. Blood and thyroid glands of pups were collected for the determination of serum T4, T3 and TSH and radioiodine uptake. Low protein diet caused a slight decrease in radioiodine uptake at 21 days, and a significant decrease in T3 levels (l28 ñ 14 vs 74 ñ 9 ng/dl, P<0.05), while T4 levels did not change and TSH was increased slightly. At 30 days, T3 and TSH did not change while there was a significant increase in both T4 levels (4.8 ñ 0.3 vs 6.1 ñ 0.2 mug/dl, P<0.05) and in radioiodine uptake levels (0.34 ñ 0.02 vs 0.50 ñ 0.030 per cent/mg thyroid, P<0.05). At 60 days serum T3, T4 and TSH levels were normal, but radioiodine uptake was still significantly increased (0.33 ñ 0.02 vs 0.41 ñ 0.03 per cent/mg thyroid, P<0.05). Thus, it seems that protein malnutrition of the dams during suckling causes hypothyroidism in the pups at 21 days that has a compensatory mechanism increasing thyroid function after refeeding with a 22 per cent protein diet. The radioiodine uptake still remained altered at 60 days, when all the hormonal serum levels returned to the normal values, suggesting a permanent change in the thyroid function.

Thyroxine and thyrotropin levels in cord blood sera from south Iran

Birth is associated with significant changes in the hypothalamic-pituitary-thyroid axis and these changes complicate the proper assessment of thyroid function in neonates. Normal values forT[4] [thyroxine] and TSH [thyroid stimulating hormone] in cord blood are not well established. The present study was carried out on 4000 specimens of cord sera of both sexes in order to establish reliable reference values for these hormones. Our data imply that the level of T[4] in cord sera [mean +/- 1 SD: 10.99:1:2.46 micro g/dL] is less than that of the neonatal period but is comparable to that of older infants. The concentration of TSH [mean +/- 1 SD:7.09+4.54 micro/mL] is comparable to the level expected in the first week of life but is higher than that of older infants. The values of T[4] and TSH obtained from cord blood of boys and girls did not show any statistically significant differences. It is suggested that these values can be used as normal reference values for T[4] and TSH in cord blood

Influence of age and sex in modulating TSH level in primary hypothyroidism

Previous studies addressing the interaction of age and sex with the function of the hypothalamic-pituitary-thyrotrophs axis yielded conflicting results, due in part to inability to control for the effect of variable free thyroid hormone levels. We studied the effect of age and sex on TSH levels in patients with severe primary hypothyroidism who have essentially undetectable plasma thyroid hormone levels. The TSH levels were measured in 116 thyroid cancer patients four weeks after the withdrawal of thyroxine therapy in preparation for radioiodine scan/treatment. All patients had a TSH >/= 30 mU/L [normal = 0.2-5] and a free T[4] <6 pmol/L [normal = 10-25]. Thirty males and 86 females with a mean age [ +/- SD] of 40 +/- 16 [range 6-89 years] were studied on up to four hypothyroid episodes, with a total of 191 episodes. The TSH level during the first hypothyroid episode correlated significantly with the TSH level during subsequent episodes [first episode versus second episode, r = 0.7, P - 0.0001; first versus third episode, r = 0.6, P - 0.03]. There was a significant negative correlation between age and TSH level [r = -0.24, P - 0.0009] that persisted when only the first hypothyroid episode was considered [r = -0.23, P = 0.01], or when only males [r = -0.32, P = 0.02] or only females [r = -0.23, P = 0.005] were considered. Means of TSH levels in males and females were not significantly different [130 versus 114 mU/L, respectively; P = 0.28]. We conclude that age but not sex may modulate the sensitivity/responsiveness of the hypothalamic-pituitary thyrotroph axis to primary hypothyroidism

La glándula tiroides...se autoregula? / The thyroid gland...itself autorregulation?

El aporte de yodo es fundamental para el normal funcionamiento de la glándula tiroides. Analizar el proceso de síntesis de las hormonas tiroideas es de vital importancia para comprender el mecanismo de autoregulación. Esta glándula posee un mecanismo intrínseco de regulación de su propio crecimiento y funcionamiento, el mismo está asociado a la concentración intratiroidea de yoduros y compuestos yodados. Estos compuestos son sintetizados por la misma glándula y parte de ellos son derivados del ácido araquidónico. El análisis de estos hechos permiten entender la etiología de disfunciones tiroideas durante el stress o la ingesta de altas concentraciones de yodo con tejido glandular normal.