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Biomedical subjects

R D Utiger

Publications and source records attributed to R D Utiger.

At least 73 records · Page 4Linked to original sources
PubMed1980

Hyperthyroidism due to excess thyrotropin secretion: follow-up studies.

Follow-up studies of a woman with hyperthyroidism due to excessive TSH secretion, previously reported (1), are described. For most of the ensuing years, she has been treated with methimazole. On several occasions, methimazole was discontinued; each time elevations of serum TSH, T4, and T3 concentrations, similar in magnitude to those originally present, occurred. Initially, her serum TSH concentrations fell substantially after dexamethasone administration and did not change after TRH. The same responses have occurred on several occasions during the follow-up period. Serum glycoprotein alpha-subunit and TSH-beta concentrations were normal and did not change after TRH administration, but serum alpha-subunit declined during dexamethasone and increased slightly after gonadotropin-releasing hormone. No increase in serum TSH occurred after TRH administration when TSH secretion was decreased by dexamethasone administration. No evidence of pituitary enlargement has developed during the 7-yr follow-up period. The cause of this patient's excessive TSH secretion remains unknown, but her TSH secretory dynamics are most consistent with those found in patients who had TSH-secreting pituitary adenomas reported in recent years.

Adult↗
PubMed1980

Thyrotropin-releasing hormone provokes abnormal follicle-stimulating hormone (FSH) and luteinizing hormone responses in men who have pituitary adenomas and FSH hypersecretion.

Serum FSH ad LH concentrations after the administration of TRH were measured in 10 men who had pituitary adenomas associated with FSH hypersecretion. Similar measurements were made in 12 men who had pituitary adenomas but no FSH hypersecretion, in 10 age-matched, normal men, and in 5 men who had primary hypergonadism. The mean serum LH concentration in the men who had pituitary adenomas and FSH hypersecretion increased 136% after TRH administration, significantly greataer (P < 0.005) than the 48% increase in the normal men or the 51% increase in the men who had pituitary adenomas without FSH hypersecretion. Serum LH did not increase at all in the men who had primary hypoganadism. The serum FSH concentration did not increase in any of the normal men, in the men who had pituitary adenomas without FSH hypersecretion, or in the men who had primary hypogonadism, but did increase in 5 of the 10 men who had FSH hypersecretion; the mean increase in these 5 men was 38%. The exaggerated LH responses and the nonspecific FSH responses to TRH of the men who had pituitary adenomas associated with FSH hypersecretion suggest that control of both FSH and LH secretion by these adenomas is abnormal and, therefore, that these adenomas are likely gonadotroph cell adenomas.

Adenoma↗
PubMed1979

Effect of tri-iodothyronine replacement on the metabolic and pituitary responses to starvation.

To determine the implication of decreased T3 production during fasting, seven normal men were fasted for 80 hours on two occasions; they received 5 microgram of T3 every three hours durnig the second fast. The mean serum T3 concentration declined during the control fast from 120 to 73 ng per deciliter (P less than 0.01), but remained slightly above base-line values during the T3 fast. Mean serum T4 concentrations did not change, and mean serum rT3 concentrations increased, during both fasts. The peak serum TSH increment after TRH was 11.1 micromicron per milliliter before fasting, 8.9 (not significant) after the control fast and 2.2 (P less than 0.01) after the T3 fast. Urea excretion was 9.1 per cent higher during the T3 fast; there were no differences in the changes in blood glucose, plasma fatty acids or other substrates during the two fasts. Pretreatment with potassium iodide lowered serum T4 concentrations and increased the serum TSH response to TRH after fasting. We conclude that the decrease in serum T3 concentrations during fasting spares muscle protein. Fasting is accompanied by a lower set point of TSH secretion, which remains sensitive to changes in serum thyroid hormone concentrations.

Adult↗
PubMed1979

Plasma triiodothyronines in fetal sheep: effects of illness and thyroidectomy.

Plasma 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine concentrations were measured in fetal sheep prior to death in utero and after thyroidectomy. In six fetal sheep who subsequently died in utero, plasma rT3 concentrations were elevated in all for 2 to 13 days prior to death. There were no consistent changes in plasma T4 concentrations. In two thyroidectomized fetal sheep, plasma T4 and rT3 concentrations fell to low levels. Plasma T3 concentrations remained low and there was no increase in plasma T3 in the last week prior to parturition like that which occurs in normal fetal sheep. Parturition was preceded by the normal increase in fetal plasma cortisol concentrations and occurred at the normal time. These data indicate that plasma rT3 concentrations are increased as a result of illness in fetal sheep and that such measurements may be useful as an indicator of fetal distress. The normal increase in plasma T3 late in gestation is not necessary for the late gestational cortisol surge or for normal parturition.

Amniotic Fluid↗
PubMed1979

Regulation of the conversion of thyroxine to triiodothyronine in the perfused rat liver.

This study was undertaken to determine what factors control the conversion of thyroxine (T(4)) to triiodothyronine (T(3)) in rat liver under conditions approximating those found in vivo. Conversion of T(4) to T(3) was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T(4) from perfusion medium and converted it to T(3). Production of T(3) by the perfused liver was a function of the size of the liver, the uptake of T(4) by the liver, and the presence of T(4)-5'-deiodinase activity. Production of T(3) was increased by increasing the uptake of T(4) by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T(4) concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T(4) to T(3). The liver had a large capacity for extracting T(4) and for T(4)-5'-deiodination to T(3), which was not saturated at a T(4) concentration of 60 mug/dl. Production of T(3) was decreased by inhibiting hepatic T(4)-5'-deiodinase with propylthiouracil, which decreased T(3) production by decreasing the conversion of T(4) to T(3). Propylthiouracil did not alter hepatic T(4) uptake. Fasting resulted in a progressive decrease in hepatic T(4) uptake to 42% of control levels by the 3rd d of fasting; this was accompanied by a proportionate decrease in T(3) production. The rate of conversion of T(4) to T(3) did not change during fasting. When T(4) uptake in 2-d-fasted rat livers was raised to levels found in fed rats by increasing the perfusate T(4) concentration from 10 to 30 mug/dl, T(3) production returned to normal. Again, no change in the rate of conversion of T(4) to T(3) was observed. These results indicate that the decreased hepatic T(3) production during fasting primarily results from decreased hepatic uptake of T(4), rather than from changes in T(4)-5'-deiodinase activity. Thus, these studies have delineated a new mechanism that functions independently of enzyme quantity or activity whereby production of T(3) from T(4) is regulated.

Animals↗
PubMed1979

Plasma clearance and plasma half-disappearance time of exogenous thyrotropin-releasing hormone and pyroglutamyl-N3im-methyl-histidyl prolineamide.

The plasma clearance rate (PCR) and plasma half-disappearance time (t1/2) of TRH was compared to the PCR and t1/2 of pyroglutamyl-N3im-methyl-histidyl prolineamide (methyl-TRH), a more potent analog of TRH in normal subjects. The PCR for TRH was 1500 +/- 329 (SD) ml/min, which was significantly greater than the PCR of methyl-TRH (783 +/- 96 ml/min). The t1/2 of TRH was 6.2 min compared to a t1/2 of 11.5 min for methyl-TRH. The slower clearance of methyl-TRH is probably due to the increased resistance to degradation by serum enzymes of methyl-TRH compared to TRH.

Half-Life↗
PubMed1978

Surge of fetal plasma triiodothyronine before birth in sheep.

Plasma thyroid hormone and cortisol concentrations were measured from early third trimester to delivery in seven pregnant ewes and their fetuses. A surge in fetal plasma triiodothyronine was found during the six days prior to delivery, the mean values rising from less than 30 to 125 ng. per deciliter. During this period the fetal plasma cortisol also increased from less than 1 to 8.1 microgram per deciliter. During this period there was no significant change in fetal plasma thyroxine (T4) or reverse T3 concentrations and no change in maternal plasma concentrations of any of these hormones. The abrupt increase in fetal plasma T3 concentrations with no rise in plasma T4 suggests that there was an alteration in extrathyroidal conversion of T4 to T3 rather than an increase in thyroid secretion, since the latter would be expected to cause an increase in both plasma T4 and plasma T3. The changes in plasma T3 and cortisol concentrations in a fetus that died in utero eight to 10 days before term resembled those occurring prior to normal parturition.

Animals↗
PubMed1978

Influence of histocompatibility and transplant site on survival.

Suggestions that endocrine tissue is privileged, in that it may not be as severely damaged by the allograft reaction, provided the stimulus for an evaluation of thyroid transplantation across various histocompatibility barriers and into a number of different recipient sites. Results of allografting reveal that Ag-B compatibility allows for prolonged survival of thyroid tissue (much longer than skin in the same histocompatibility combinations) in the following sites: intramuscular, intradermal, renal subcapsular, and anterior chamber. Only the intrasplenic site, however, did not allow survival of even weakly incompatible grafts. In addition, all recipients of thyroid allografts rejected subsequent donor strain skin grafts in an accelerated manner, attesting to the normal antigenicity of thyroid. This finding, that thyroid is a "relatively privileged" tissue, has not been reported previously and is encouraging, since it suggests the potential success of clinical transplantation of other endocrine tissue less easily replaced than thyroid by administration of naturally occurring of synthetic analogues. Further, mild immunosuppression may serve to prolong survivals of allografts of endocrine tissue such as parathyroid or pancreatic islets, especially if an immunologically privileged site is employed.

Animals↗
PubMed1978

Iodothyronine metabolism in rat liver homogenates.

To investigate mechanisms of extrathyroidal thyroid hormone metabolism, conversion of thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)) and degradation of 3,3',5'-triiodothyronine (rT(3)) were studied in rat liver homogenates. Both reactions were enzymatic. For conversion of T(4) to T(3), the K(m) of T(4) was 7.7 muM, and the V(max) was 0.13 pmol T(3)/min per mg protein. For rT(3) degradation, the K(m) of rT(3) was 7.5 nM, and the V(max) was 0.36 pmol rT(3)/min per mg protein. Production of rT(3) or degradation of T(4) or T(3) was not detected under the conditions employed. rT(3) was a potent competitive inhibitor of T(4) to T(3) conversion with a K(i) of 4.5 nM; 3,3'-diiodothyronine was a less potent inhibitor of this reaction. T(4) was a competitive inhibitor of rT(3) degradation with a K(i) of 10.2 muM. Agents which inhibited both reactions included propylthiouracil, which appeared to be an allosteric inhibitor, 2,4-dinitrophenol, and iopanoic acid. Sodium diatrizoate had a weak inhibitory effect. No inhibition was found with alpha-methylparatyrosine, Fe(+2), Fe(+3), reduced glutathione, beta-hydroxybutyrate, or oleic acid. Fasting resulted in inhibition of T(4) to T(3) conversion and of rT(3) degradation by rat liver homogenates which was reversible after refeeding. Serum T(4), T(3), and thyrotropin concentrations fell during fasting, with no decrease in serum protein binding as assessed by a T(3)-charcoal uptake. There was no consistent change in serum rT(3) concentrations. Dexamethasone had no effect in vitro. In vivo dexamethasone administration resulted in elevated serum rT(3) concentrations after 1 day, and after 5 days, in inhibition of T(4) to T(3) conversion and rT(3) degradation without altering serum T(4), T(3), or thyrotropin concentrations. Endotoxin treatment had no effect of iodothyronine metabolism in liver homogenates. In kidney homogenates the reaction rates and response to propylthiouracil in vitro were similar to those in liver. No significant T(4) to T(3) conversion or rT(3) production or degradation could be detected in other tissues. These data suggest that one iodothyronine 5'-deiodinase is responsible for both T(4) to T(3) conversion and rT(3) degradation in liver and, perhaps, in kidney. Alterations in serum T(3) and rT(3) concentrations induced by drugs and disease states may result from decreases in both T(3) production and rT(3) degradation consequent to inhibition of a single reaction in the pathways of iodothyronine metabolism.

Animals↗