Effect of Thyroxine on the Inactivation of Thyrotrophin‐releasing Hormone by Rat and Human Plasma

Dupont, André; Labrie, Fernand; Levasseur, L.; Dussault, J H

doi:10.1111/j.1365-2265.1976.tb01961.x

Cited by 26 publications

(13 citation statements)

References 16 publications

(14 reference statements)

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“…In the adult samples studied, there was no correlation between TRH-degrading activity and the age of the individual (18-77 yr for females and 26-73 yr for males). The wide range of TRH-degrading activity in euthyroid adult serum confirms the observation of Bassiri and Utiger (8) and Dupont et al (18). The elevated TSH and low T3 levels in cord serum (Table II) are consistent with what has been reported (1-3).…”

Section: Measurement Of Trh-degrading Activitysupporting

confidence: 82%

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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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Section: Measurement Of Trh-degrading Activitysupporting

confidence: 82%

“…TRH is present in the fetal hypothalamus (21) and in the placenta (22). It is also of interest that TRH (23)(24)(25), TRH receptors (26), and TRH-degrading activity (16) (18,27,28 …”

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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“…Another TRH antiserum with a weak titer (1:4,000) had no Thyrotropin-Releasing Hormone Antibody Blockade studies, the decrease in serum TSH persisted up to 2 h in only one experiment. Serum TRH has been reported to be similar in the normal and hypothyroid rat (39,45) and the serum TRH degrading enzyme activity lower in hypothyroid man and rat (46,47 (50) and rat pituitary cell cultures (51). Furthermore, preliminary data suggest that both serum TSH and serum Prl concentrations rise during proestrus in the rat (52).…”

Section: Discussionmentioning

confidence: 99%

The Physiological Role of Thyrotropin-Releasing Hormone in the Regulation of Thyroid-Stimulating Hormone and Prolactin Secretion in the Rat

Harris¹,

Christianson²,

Smith³

et al. 1978

J. Clin. Invest.

119

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A B S T R A C T The physiological role of thyrotropinreleasing hormone (TRH) in the regulation of thyrotropin (thyroid-stimulating hormone, TSH) and prolactin (Prl) secretion has been assumed but not proven. Stimulation of their release requires pharmacologic doses of TRH. Lesions of the hypothalamus usually induce an inhibition of TSH secretion and an increase in Prl. To determine whether TRH is essential for TSH and Prl secretion in the rat, 0.1 ml of TRH antiserum (TRH-Ab) or normal rabbit serum was administered to normal, thyroidectomized, cold-exposed, and proestrus rats through indwelling atrial catheter. Serum samples were obtained before and at frequent intervals thereafter. Serum TSH concentrations in normal, thyroidectomized, cold-exposed, and proestrus rats were not depressed in specimens obtained up to 24 h after injection of normal rabbit serum. In contrast, serum TSH was significantly decreased after the administration of TRH-Ab in all normal (basal, 41±8 AU/ml [mean±SE]; 30 min, 6+-2; 45 min, 8+3; 75 min, 4±2); thyroidectomized (basal, 642+32 ,uU/ml; 30 min, 418±32; 60 min, 426±36; 120 min, 516±146); coldstressed (basal, 68±19 uU/ml; 30 min, 4±3; 180 min, 16±8); and proestrus (basal, 11 a.m., 57±10,U/ml; 1 p.m., 20±3; 3 p.m., 13±4; 5 p.m., 19±3) rats. However, 0.1 ml of TRH-Ab had no effect on basal Prl concentrations in normal or thyroidectomized rats and did not prevent the Prl rise in rats exposed to cold (basal, 68+7 ng/ml; 15 min, 387±121; 30 min, 212+ 132; 60 min, 154+114), or the Prl surge observed on the afternoon of proestrus (basal 11 a.m., 23±2 ng/ml; 1 p.m., 189±55; 3 p.m., 1,490±260; 5 p.m., 1,570+286). These studies demonstrate that TRH is required for TSH secretion in the normal, cold-exposed and proestrus rat and contributes, at least in part, to TSH secretion in the hypothyroid rat, but is not required for Prl secretion in these states. INTRODUCTIONThe administration of pharmacologic doses of thyrotropin-releasing hormone (TRH)' has been demonstrated to stimulate thyrotropin (thyroid-stimulating hormone, TSH) and prolactin (Prl) synthesis and release from the anterior pituitary (1-5). Surgical or pathologic lesions ofthe hypothalamus have resulted in decreased TSH release and subsequent hypothyroidism (6)(7)(8)(9)(10). It is well established that Prl secretion is tonically suppressed by dopamine either by a direct effect on the pituitary or by modulating the release of the Prl inhibiting factor. Median eminence and pituitary stalk lesions usually enhance rather than suppress Prl secretion (11,12), although this is not always observed in unstressed rats after hypothalamic deafferentation (13). In intact animals, electrical stimulation of the hypothalamic "hypophysiotropic area" (14) has been shown to increase serum TSH levels (10,15), presumably secondary to TRH release, although direct experimental evidence of enhanced TRH release is lacking. The effect of such electrical stimulation on Prl secretion is variable (16). The alterations in TSH or Prl release after hypothalamic lesion...

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“…This interpretation was supported by the findings that the activities of the particulate liver enzyme, like the serum enzyme [16][17][18], is also regulated by thyroid hormones [19]. Moreover, similar enzymechemical properties between the particulate liver enzyme and the serum enzyme were noticed [9,15].…”

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confidence: 61%

Purification and characterization of the thyrotropin‐releasing hormone (TRH)‐degrading serum enzyme and its identification as a product of liver origin

Schmitmeier¹,

Thole²,

Bader

et al. 2002

European Journal of Biochemistry

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Previous biochemical studies have indicated that the membrane-bound thyrotropin-releasing hormone (TRH)-degrading enzyme (TRH-DE) from brain and liver and the serum TRH-DE are derived from the same gene. These studies also suggested that the serum enzyme is of liver origin. The present study was undertaken to verify these hypotheses. In different species, a close relationship between the activities of the serum enzyme and the particulate liver enzyme was noticed. The activity of the serum enzyme decreased when rats were treated with thioacetamide, a known hepatotoxin. With hepatocytes cultured in a sandwich configuration, release of the TRH-DE into the culture medium could also be demonstrated. The trypsin-solubilized particulate liver TRH-DE and the serum TRH-DE were purified to electrophoretic homogeneity. Both enzymes and the brain TRH-DE were recognized by a monoclonal antibody generated with the purified brain enzyme as antigen. Lectin blot analysis indicated that the serum enzyme and the liver enzyme are glycoproteins containing a sugar structure of the complex type, whereas the brain enzyme exhibits an oligomannose/hybrid glycostructure. A molecular mass of 97 000 Da could be estimated for all three enzymes after deglycosylation and SDS/PAGE followed by Western blotting. Fragment analysis of the serum TRH-DE revealed that the peptide sequences correspond to the cDNA deduced amino-acid sequences of the membrane-bound brain TRH-DE, whereby two peptides were identified that are encoded by exon 1. These data strongly support the hypothesis that the TRH-DEs are all derived from the same gene, whereby the serum enzyme is generated by proteolytic cleavage of the particulate liver enzyme.Keywords: TRH-degrading enzyme (TRH-DE); serum; liver; brain; characterization.The signal substance thyrotropin-releasing hormone (TRH), a hypothalamic hypophysiotropic neuropeptide hormone (reviewed in [1,2]) and a peptidergic neurotransmitter/neuromodulator (reviewed in [3,4]), is known to be rapidly inactivated by the brain TRH-degrading enzyme (TRH-DE), an ectoenzyme located on the surface of neuronal cells, as well as by the soluble serum TRH-DE. The highest activity of the membrane-bound TRH-DE is found in brain and significant activities are also detected in retina, lung and liver but not in other tissues such as heart, kidney and muscle [5][6][7]. Because the membrane-bound brain TRH-DE and the serum TRH-DE exhibit the same extraordinary high degree of substrate specificity and identical enzyme-chemical characteristics [8][9][10][11][12][13][14] it has been suggested that both enzymes are derived from the same gene.Based on the observation that the developmental pattern of the particulate liver TRH-DE and the serum TRH-DE are almost identical it has been proposed that the serum TRH-DE, like most serum enzymes and proteins, might be of liver origin [9,15]. This interpretation was supported by the findings that the activities of the particulate liver enzyme, like the serum enzyme [16][17][18], is also regulated by thyroid h...

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Effect of Thyroxine on the Inactivation of Thyrotrophin‐releasing Hormone by Rat and Human Plasma

Cited by 26 publications

References 16 publications

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

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

The Physiological Role of Thyrotropin-Releasing Hormone in the Regulation of Thyroid-Stimulating Hormone and Prolactin Secretion in the Rat

Purification and characterization of the thyrotropin‐releasing hormone (TRH)‐degrading serum enzyme and its identification as a product of liver origin

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