In vitro Plasma Inactivation of Thyrotropin Releasing Factor (TRF) and Related Peptides. Its Inhibition by Various Means and by the Synthetic Dipeptide PCA-His-OME

Vale, Wylie; Burgus, Roger; Dunn, Thomas F.; Guillemin, Roger

doi:10.1159/000178234

Cited by 41 publications

(20 citation statements)

References 10 publications

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“…This value corresponds closely with current estimates of extracellular fluid volume in normal human subjects (11). The finding of a large TRH distribution volume is not unexpected in view of the small molecular size of TRH and the lack of evidence for binding of TRH to plasma protein (4,12).…”

Section: Discussionsupporting

confidence: 86%

“…These results, plus the observations that TRH is inactivated Received for publication 21 November 1972 and in revised form 12 January 1973. rapidly by human plasma or serum in vitro (3,4), suggested that TRH rapidly disappears from the circulation in vivo. The present study was undertaken to determine the magnitude of plasma TRH concentrations that follow its intravenous administration and its rate of disappearance and metabolic fate.…”

Section: Introductionmentioning

confidence: 81%

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Metabolism and Excretion of Exogenous Thyrotropin-Releasing Hormone in Humans

Bassiri¹,

Utiger²

1973

J. Clin. Invest.

109

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A B S T R A C T To study the metabolism of thyrotropinreleasing hormone (TRH) in vivo, 400 Ag TRH was administered intravenously to eight normal male subjects. Multiple plasma and urine samples were obtained before and after TRH administration. Serum TSH concentrations increased after TRH administration in all subjects. Plasma TRH levels, measured by radioimmunoassay, were undetectable (< 0.4 ng/ml) before TRH administration. Plasma TRH concentrations averaged 33±7 ng/ml (mean +SEM) 2 min after TRH injection. Thereafter, they decreased rapidly so that the mean plasma TRH level was 2.9 ng/ml 20 min after TRH administration. The fall in plasma TRH levels was linear during this interval. Thereafter TRH levels declined more slowly. The mean half-life (ti) of TRH was 5.3±0.5 min. The mean distribution volume was 15.7 ±3.8 liters, an average of 16.5% of body weight in these subjects. In the urine, 5.5±0.9% of the administered TRH was recovered in the 3 h after TRH administration. Of the total urinary TRH recovered, 84.9% was excreted in the first 30 min. These results indicate that TRH is distributed in a large volume, that it is rapidly metabolized and that a significant quantity of administered TRH is excreted in the urine. INTRODUCTIONThe administration of thyrotropin-releasing hormone (TRH)' to normal subjects is followed by a prompt increase in serum thyrotropin (TSH) concentrations.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 81%

Metabolism and Excretion of Exogenous Thyrotropin-Releasing Hormone in Humans

Bassiri¹,

Utiger²

1973

J. Clin. Invest.

109

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“…'Grafted' and intact rats (120 g females) were injected with 25 ftCi ,2SI. Three days later they were transferred to a wellventilated and light-regulated hot room (35 ±0.5°C, 12 h light from 6 a.m. each day) for TRH studies [Vale et at.. 1971], The rats were housed in wire cages with elevated floors and given food and water ad lib. Starting 3 days after the elevation in ambient temperature and on successive days thereafter, TRH was injected into the conscious rat via the tail vein (dose range 3.3 to 270 ng TRH/rat).…”

Section: Methodsmentioning

confidence: 99%

The Response of the Heterotopic Pituitary to Thyrotropin Releasing Hormone (TRH)

Sirett¹,

Purves²

1974

Neuroendocrinology

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The ability of pituitary glands grafted beneath thekidney capsule to mediate a discharge of ¹²⁵I from the thyroid gland in response to i. v. injections of TRH was evaluated by blood ¹²⁵I measurements. The minimum effective dose (3.3 ng TRH/rat) was less than that found for rats with intact pituitaries under the same conditions (10 ng TRH/rat). At higher dose levels the intact rats gave bigger responses than did rats with heterotopic pituitaries. The heterotopic pituitary retains its sensitivity to the releasing action of TRH but the magnitude of its responses is limited by the small amount of TSH available for release.

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“…Vials were counted for 10 min. TRH degraded was calculated by adding the radioactivity in the TRH sections and comparing it with that obtained from a control incubation with heat-inactivated serum (30 min, 55°C) (6)(7)(8). 90% of the applied radioactivity was recovere(I on the strips.…”

Section: Measurement Of Trh-degrading Activitymentioning

confidence: 99%

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

Neary¹,

Nakamura²,

Davies³

et al. 1978

J. Clin. Invest.

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A B S T R A C T Thyrotropin-releasing hormone (TRH)-degrading activity was investigated in human cord, maternal, and euthyroid adult sera by measuring (a) the rate of disappearance of TRH and (b) the rate of formation of degradation products. The rate of TRH degradation in cord and maternal sera was 25-33% of that in euthyroid adult serum. Concomitantly, in cord and maternal sera, the rate offormation ofproline, a major TRH degradation product in serum, was one-quarter to onethird that in euthyroid adult sera. The differences were highly significant (P <0.001). The decreased levels of TRH-degrading activity in cord and maternal sera cannot be explained by (a) the presence of a dialyzable inhibitor, (b) the absence of an activator of TRH degradation, or (c) a reversal of the degradation process. There was no difference in the types of radioactive degradation products formed by cord, maternal, and euthyroid adult sera.The low level of TRH-degrading activity and its possible relationship to high thyrotropin-stimulating hormone levels in cord serum suggest that TRH-degrading activity may be a factor to consider in investigations of the perinatal pituitary-thyroid axis, but further studies are needed to determine the role of serum degradation of TRH in regulating physiological levels of TRH.

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In vitro Plasma Inactivation of Thyrotropin Releasing Factor (TRF) and Related Peptides. Its Inhibition by Various Means and by the Synthetic Dipeptide PCA-His-OME

Cited by 41 publications

References 10 publications

Metabolism and Excretion of Exogenous Thyrotropin-Releasing Hormone in Humans

Metabolism and Excretion of Exogenous Thyrotropin-Releasing Hormone in Humans

The Response of the Heterotopic Pituitary to Thyrotropin Releasing Hormone (TRH)

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

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