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Biomedical subjects

C H Emerson

Publications and source records attributed to C H Emerson.

At least 19 recordsLinked to original sources
PubMed1998

Urinary compound W in pregnant women is a potential marker for fetal thyroid function.

OBJECTIVE: Previously we reported 3,3'-diiodothyronine sulfate-like material (compound W) in maternal serum, and studies suggest that compound W is derived from thyroid hormones of fetal origin. In this study we characterized gestational changes of urinary compound W concentrations to correlate with changes in serum concentrations. STUDY DESIGN: Urinary samples were collected from 94 women at various gestational ages ranging from 3 to 40 weeks. Urinary compound W was first identified biochemically. The concentrations of compound W (adjusted for creatinine levels) were assessed by a 3,3'-diiodothyronine sulfate radioimmunoassay in ethanol extracts of urine samples. RESULTS: Compound W increased to 88 +/- 1.4 pmol (of 3,3'-diiodothyronine sulfate equivalent)/mmol creatinine in urinary samples obtained from 26 women in the first trimester of pregnancy compared with 40 +/- 6.9 pmol/mmol creatinine in 10 nonpregnant women. Excretion of compound W increased further during the second and third trimesters: 171 +/- 17 (n = 18) and 434 +/- 26 (n = 50) respectively. In contrast, urinary 3,3',5-triiodothyronine sulfate concentrations measured by radioimmunoassay were similar during pregnancy to values in nonpregnant women. CONCLUSIONS: Urinary compound W concentrations increase with the progression of normal pregnancy and correlate with the increase in serum levels. Random spot urine compound W concentrations, adjusted for creatinine levels, may be used in place of serum levels in conditions in which obtaining serum samples may be technically difficult, especially during population screening.

Biomarkers↗
PubMed1998

The effect of recombinant human thyrotropin (rhTSH) on thyroid function in mice and rats.

The vast majority of studies to determine the biological activity of recombinant human thyrotropin (rhTSH) have been carried out in the mouse. We have recently reported that 0.1 mg of rhTSH IM (one-ninth the dose given in thyroid cancer patients) given to normal subjects elicits a brisk rise in serum thyroxine (T4), triiodothyronine (T3), and thyroglobulin (Tg) concentrations. In contrast, in initial studies in the rat, a low dose of rhTSH failed to increase serum T4 or T3 concentrations. The present study was, therefore, carried out to determine the biological activity of rhTSH in euthyroid and in T3-treated, TSH-suppressed rats and mice. Doses of rhTSH based on body weight were used and resulted in similar serum human thyrotropin (hTSH) concentrations in the two species. Euthyroid and TSH-suppressed mice responded briskly to rhTSH administration. In contrast, serum T4 did not increase after rhTSH administration in euthyroid rats. In TSH-suppressed rats, the increase in serum T4 was similar to that observed in TSH suppressed mice. These observations suggest that rhTSH more readily displaces endogenous TSH from the mouse than from the rat thyroid TSH receptor, because equal responses were observed when endogenous TSH was suppressed.

Animals↗
PubMed1998

Arcuate nucleus ablation prevents fasting-induced suppression of ProTRH mRNA in the hypothalamic paraventricular nucleus.

Fasting results in reduced thyroid hormone levels and inappropriately low or normal thyroid-stimulating hormone (TSH), partly attributed to central hypothyroidism due to suppression of pro TRH gene expression in the hypothalamic paraventricular nucleus. Recently, we demonstrated that the systemic administration of leptin to fasting animals restores plasma thyroxine (T4) and proTRH mRNA in the paraventricular nucleus to normal, suggesting that the fall in circulating leptin levels during fasting acts as a signal to hypophysiotropic neurons in the paraventricular nucleus to reset the set point for feedback regulation of pro TRH mRNA by thyroid hormone. To determine whether the effect of fasting on the hypothalamic-pituitary-thyroid axis is mediated through the hypothalamic arcuate nucleus where leptin receptors are highly concentrated, we studied the effect of fasting and exogenous leptin administration on plasma thyroid hormone levels and proTRH mRNA concentration in the paraventricular nucleus in adult animals with arcuate nucleus lesions induced pharmacologically by the neonatal administration of monosodium L-glutamate (MSG). In normal animals, fasting reduced plasma T4 and TSH levels and the concentration of proTRH mRNA in the hypothalamic paraventricular nucleus. In contrast, neither fasting nor leptin administration to fasting MSG-treated animals had any significant effects on plasma thyroid hormone and TSH levels and proTRH mRNA in the paraventricular nucleus. These studies suggest that during fasting, the arcuate nucleus is essential for the normal homeostatic response of the hypothalamic-pituitary-thyroid axis and may serve as a critical locus to mediate the central actions of leptin on proTRH gene expression in the paraventricular nucleus.

Animals↗
PubMed1998

Vasopressin messenger ribonucleic acid regulation via the protein kinase A pathway.

Activation of vasopressin (VP) gene expression in vivo by osmotic stimuli results in an increase in both messenger RNA (mRNA) content and polyadenylate [poly(A)] tail length. VP gene transcription in vitro is stimulated by protein kinase A (PKA) activation. To examine the role of PKA in the regulation of VP mRNA poly(A) metabolism, constructs of the rat VP gene were permanently transfected into the mouse anterior pituitary cell line, AtT-20. Treatment with forskolin of cells expressing the intact VP gene resulted in increased VP gene transcription, an increase in the content of VP mRNA, and a shift toward VP mRNA species with longer poly(A) tails accompanied by the loss of VP mRNA species with shorter poly(A) tails. We uncoupled the PKA-stimulated appearance of long-tailed species from the disappearance of short-tailed species, suggesting that the size shift was caused by a coincident, but uncoupled net increase in VP mRNA species with elongated poly(A) tails and net loss of mRNA species with short poly(A) tails. These data indicate that activation of the PKA second-messenger pathway both enhances transcription of the VP gene and causes an increase in the average length of VP mRNA poly(A) tails. This latter effect, by shifting upwards the average poly(A) tail size, could result in increased translational efficiency or stability of VP mRNA, thereby providing an additional mechanism by which PKA may enhance gene expression.

Animals↗
PubMed1998

Circulating iodide concentrations during and after pregnancy.

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.

Adult↗
PubMed1997

Postpartum thyroid dysfunction.

Four disorders of the postpartum period are associated with thyroid dysfunction. The most common is PPT. Although recovery from thyroid dysfunction often occurs in PPT, many patients eventually develop permanent hypothyroidism. Postpartum Graves' Disease is less common than PPT, but it is not unusual. Whereas antithyroid drugs are indicated for postpartum Graves' Disease, they are not useful in PPT. Although they are rare, lymphocytic hypophysitis and postpartum pituitary infarction are important entities because they cause deficiencies of many critical hormones. The autoimmune nature of PPT, postpartum Graves' disease, and lymphocytic hypophysitis highlights the unique effects of pregnancy on the immune system.

Diagnosis, Differential↗
PubMed1997

Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus.

Prolonged fasting is associated with a number of changes in the thyroid axis manifested by low serum T3 and T4 levels and, paradoxically, low or normal TSH. This response is, at least partly, caused by suppression of proTRH gene expression in neurons of the hypothalamic paraventricular nucleus (PVN) and reduced hypothalamic TRH release. Because the fall in thyroid hormone levels can be blunted in mice by the systemic administration of leptin, we raised the possibility that leptin may have an important role in the neuroendocrine regulation of the thyroid axis, through effects on hypophysiotropic neurons producing proTRH. Adult male, Sprague-Dawley rats were either fed normally, fasted for 3 days, or fasted and administered leptin at a dose of 0.5 microg/gm BW i.p. every 6 h. Fasted animals showed significant reduction in plasma total and free T4 and T3 levels compared with controls, that were restored toward normal by the administration of leptin. Percent free T4, but not percent free T3, increased during fasting, further suggesting a reduction in plasma transthyretin levels that did not return to fed levels after leptin administration. By semiquantitative analysis of in situ hybridization autoradiograms, proTRH messenger RNA in medial parvocellular PVN neurons was markedly suppressed in the fasting animals but was restored to normal by leptin administration [fed vs. fast vs. fast/leptin (density units x 10(8)): 8.5 +/- 0.4, 3.2 +/- 0.2, 8.1 +/- 0.8]. In contrast, proTRH messenger RNA in adjacent neurons in the lateral hypothalamus that do not have a hypophysiotropic function remained unchanged by any of the experimental manipulations. These findings indicate that leptin has a selective, central action to modulate the hypothalamic-pituitary-thyroid axis by regulating proTRH gene expression in the PVN but does not have peripheral effects on thyroid-binding proteins. We propose that the fall in circulating leptin levels during fasting resets the set point for feedback inhibition by thyroid hormones on the biosynthesis of hypophysiotropic proTRH, thereby allowing adaptation to starvation.

Animals↗
PubMed1997

Recombinant human thyrotropin is a potent stimulator of thyroid function in normal subjects.

Recombinant human TSH (rhTSH) is known to stimulate 131I uptake and thyroglobulin (Tg) release from the postoperative remnant and metastases in thyroid cancer patients, but its effects on serum thyroid hormone and Tg concentrations in normal subjects have not been reported. Before using rhTSH in the management of thyroid disorders other than cancer, the thyroid response to rhTSH in normal subjects must be assessed. Six subjects, two men and four women, without evidence of thyroid disease, including normal serum free T4 index and TSH concentrations and negative tests for antithyroid peroxidase and Tg, were studied. Each received 0.1 mg rhTSH, im, 11% of the lowest dose that has been administered to thyroid cancer patients. Blood was obtained before; 2, 4, and 8 h after; and 1, 2, 3, 4, 7, and about 3 weeks after rhTSH administration. Serum TSH significantly increased at 2 h (mean +/- SE, 2.4 +/- 0.9 to 40.7 +/- 7.4 mU/mL), peaked at 4 h (50.9 +/- 9.3), remained significantly elevated for 1 day, and was significantly below baseline (0.8 +/- 0.5) 7 days after rhTSH administration. Serum T3 increased significantly at 4 h (115 +/- 4 to 190 +/- 14 ng/dL), peaked at 24 h (217 +/- 23 ng/dL), and remained significantly elevated for 3 days (151 +/- 12 ng/dL). Serum T4 increased significantly at 8 h (7.3 +/- 0.2 to 9.8 +/- 0.4 micrograms/dL), peaked at 24 h (11.2 +/- 0.5 micrograms/dL), and remained significantly elevated for 4 days (9.4 +/- 0.5 micrograms/dL). Serum Tg did not change for the first 8 h, increased significantly at 1 day (15.9 +/- 3.9 to 34.7 +/- 6.0 ng/mL), peaked at 2 days (44.2 +/- 7.0 ng/mL), and remained significantly elevated for 4 days (37.7 +/- 13.7 ng/mL). All values returned to baseline at 3 weeks. TSH antibodies were not detected at 3 weeks. A single dose of 0.1 mg rhTSH is a potent stimulator of thyroid function in normal subjects. rhTSH may be a useful agent to test thyroid reserve and for use in clinical settings that require direct thyroid stimulation.

Adult↗
PubMed1996

Comparison of the effects of propylthiouracil and selenium deficiency on T3 production in the rat.

Selenium deficiency and propylthiouracil (PTU) treatment both decrease hepatic type I T4 5'-deiodinase activity (5'D-I), which is considered to be an important regulator of the serum T3 derived from peripheral T4 to T3 conversion (T3 neogenesis). The effects of PTU treatment or a selenium-deficient diet on T4 and T3 kinetics were compared in thyroid-ablated rats infused with stable T4 to determine whether PTU treatment is a more potent inhibitor of T3 neogenesis than selenium deficiency and to compare the degree of inhibition of T3 production with the degree of inhibition of 5'D-I. PTU treatment and selenium deficiency (Se-) did not affect the T3 MCR (control, 46.0 +/- 2.5; PTU, 41.7 +/- 2.8; Se-, 41.1 +/- 4.0 ml/h.100 g BW), but did reduce serum T3 concentrations by 29% and 25%, respectively (control, 58.7 +/- 2.6; PTU, 41.5 +/- 1.0; Se-, 43.9 +/- 2.7 ng/dl; P < 0.01 for PTU or Se- vs. control) and the T3 production rate by 35% and 32%, respectively (control, 26.6 +/- 1.0; PTU, 17.3 +/- 2.0; Se-, 18.0 +/- 1.9 ng/h.100 g BW; P < 0.01 for PTU or Se- vs. Control). PTU treatment and selenium deficiency significantly increased serum T4 concentrations by 36% and 32%, respectively, due to a decrease in T4 MCR (control, 1.4 +/- 0.1; PTU, 1.1 +/- 0.1; Se-, 1.1 +/- 0.04 ml/h.100 g BW; P < 0.05 for PTU or Se- vs. control). Assuming that the concentration of T4 available for T3 neogenesis is proportional to the serum T4 concentration, the increase in serum T4 concentrations caused by PTU treatment or Se- would probably have proportionally increased the rate of T3 neogenesis. Based on these considerations, the apparent decrease in T3 neogenesis in the PTU-treated animals was 52%. This is less than the 79% and 67% inhibition of 5'D-I noted, respectively, in the liver and kidneys of these rats. Similarly, the apparent decrease in T3 neogenesis in the Se- rats was 48%, again less than the 85% and 64% inhibition of 5'D-I in their liver and kidneys, respectively. These studies suggest that PTU and Se- have similar effects on T3 neogenesis. The more potent effects of these treatments on liver and kidney 5'D-I activities than on T3 neogenesis suggest that the activities of these enzymes in these tissues are not the only important determinants of the serum T3 that is derived from nonthyroidal sources.

Animals↗
PubMed1996

Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5'-deiodinase type I inhibitor 6-anilino-2-thiouracil.

Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5'D-I activity is markedly decreased.

Aniline Compounds↗
PubMed1994

Suppression of thyrotropin-releasing hormone gene expression by interleukin-1-beta in the rat: implications for nonthyroidal illness.

Nonthyroidal illness is characterized by low thyroid hormone levels and inappropriately normal or decreased TSH levels. To determine whether the hypothalamus contributes to these responses, TRH gene expression in hypophysiotropic neurons of the paraventricular nucleus (PVN) was investigated using semiquantitative in situ hybridization histochemistry in an animal model of nonthyroidal illness. Following the systemic administration of bacterial lipopolysaccharide (LPS; 250 micrograms/100 g BW), plasma T4, T3 and TSH were reduced but this was not associated with an increase in the content of proTRH mRNA in the PVN as occurs when plasma T4 and T3 concentrations fall during primary hypothyroidism. Constant infusion of human interleukin-1 beta (IL-1 beta) into the cerebrospinal fluid also reduced plasma T4 concentration. This persisted for the duration of the infusion but TSH was only suppressed after 7 days of infusion when body weight had declined. By 24 h, the content of proTRH mRNA in the PVN in IL-1 beta infused animals was significantly reduced from control values. These studies indicate that the peripheral administration of endotoxin or central administration of IL-1 beta in the rat is associated with a proTRH mRNA content in the PVN that may be inappropriately normal or reduced for the level of circulating thyroid hormone. We propose that the inability of hypophysiotropic neurons to induce TRH gene expression in nonthyroidal illness, when circulating thyroid hormone levels are low, is one of several factors that contributes to the inability of the anterior pituitary to increase its secretion of TSH.

Animals↗
PubMed1993

Documentation of parathyroid carcinoma fifteen years after resection of a parathyroid 'adenoma'.

This report describes a 40-year-old man in whom the diagnosis of parathyroid carcinoma was made almost 15 years after resection of the primary lesion. The case emphasizes the importance of recognizing pre and intraoperative factors that differentiate between parathyroid adenoma and carcinoma and illustrates that surgical palliation is feasible in selected patients with parathyroid carcinoma.

Adenoma↗
PubMed1993

Gene expression and serum thyroxine-binding globulin are regulated by adrenal status and corticosterone in the rat.

Supraphysiological doses of glucocorticoids reduce serum T4-binding globulin (TBG) concentrations when administered to human subjects. Studies were performed in rats to determine if glucocorticoid administration alters serum TBG in another species, if circulating concentrations of glucocorticoids tonically affect serum TBG concentrations, and if changes in TBG production are likely to be a cause of the glucocorticoid-induced changes in serum TBG concentrations that are observed in humans. The serum TBG-binding capacity was 14.9 +/- 2.3 nmol/liter in adrenalectomized male rats compared to 6.6 +/- 1.0 nmol/liter in intact male rats and 4.8 +/- 0.9 nmol/liter in adrenalectomized male rats that received corticosterone in a dose equal to or less than the replacement dose, as assessed by thymus weight (P < 0.01 for serum TBG in adrenalectomized vs. intact or adrenalectomized corticosterone-treated groups). Hepatic TBG mRNA content, as assessed by polymerase chain reaction amplification and expressed as a ratio of beta-actin mRNA content, was 0.10 +/- 0.03 density units in intact male rats, 0.59 +/- 0.17 density units in adrenalectomized male rats, and 0.05 +/- 0.02 density units in adrenalectomized corticosterone-treated male rats (P < 0.03 for adrenalectomized vs. intact or adrenalectomized corticosterone-treated rats). Adrenalectomy increased the serum TBG-binding capacity in female rats (intact female rats, 13.9 +/- 1.0 nmol/liter; adrenalectomized female rats, 39.0 +/- 6.4 nmol/liter; P < 0.01). These studies indicate that serum TBG is tonically down-regulated by adrenal glucocorticoids, because corticosterone decreases the TBG production rate, probably at the level of transcription. This effect is similar to that described for corticosterone-binding globulin, but differs from that for many proteins of the serine protease inhibitor family that are related to TBG.

Actins↗