Effect of Thyroid Status on the Thyrotrophin-Releasing Hormone-Degrading Activity of Rat Serum

White, N. E.; Jeffcoate, S. L.; Griffiths, E.C.; Hooper, K. C.

doi:10.1677/joe.0.0710013

Cited by 45 publications

(24 citation statements)

References 11 publications

(16 reference statements)

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“…In addition, we observed an increase in pyroglutamyl peptidase II mRNA in rat liver 16 h following treatment with a single dose of T 3 (table 3). It is well established that chronic T 3 treatment increases the serum level of thyroliberinase in rats [16]. In an earlier study [18] we reported no effect on serum pyroglutamyl peptidase II activity 24 h after a single subcutaneous dose of 100 µg T 3 per rat but found a significant elevation after 10 days of treatment.…”

Section: Discussionmentioning

confidence: 51%

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Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

Lin

Wilk²

1998

Neuroendocrinology

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The distribution of the mRNA of the specific thyrotropin-releasing-hormone (TRH)-degrading enzyme pyroglutamyl peptidase II (EC 3.4.19.6) in rat tissues and brain regions and its regulation in rat tissues and in GH3 cells was studied by a reliable and quantitative solution hybridization ribonuclease protection assay. The distribution of pyroglutamyl peptidase II mRNA levels was uneven with the highest level of mRNA found in brain. Within brain the distribution of pyroglutamyl peptidase II mRNA was heterogeneous. A single dose of T₃ markedly increased the level of pyroglutamyl peptidase II mRNA in the pituitary (p < 0.01) and in the liver (p < 0.05). In GH3 cells, exposure to T₃ at concentrations from 10^–10 to 10^–6M for time periods of 2–24 h, did not change pyroglutamyl peptidase II mRNA levels. Acute administration of TRH to rats had no effect on pyroglutamyl peptidase II mRNA levels. By contrast, TRH down-regulated pyroglutamyl peptidase II mRNA in GH3 cells. A similar effect was produced in GH3 cells by activators of protein kinase C. These studies reveal fundamental differences in the mechanism of regulation of pyroglutamyl peptidase II mRNA in pituitary and in GH3 cells. Elevation of pyroglutamyl peptidase II mRNA in liver by T₃ suggests that this organ is the source of the enzyme in serum.

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Section: Discussionmentioning

confidence: 51%

“…Thyroid hormone was shown to increase pyroglutamyl peptidase II (thyroliberinase) activity in rat serum [16], adenohypophysis [17], frontal cortex [18] and liver [19]. The time course of the effect of thyroid hormone is consistent with a role for this hormone in increasing synthesis of pyroglutamyl peptidase II.…”

Section: Introductionmentioning

confidence: 84%

Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

Lin

Wilk²

1998

Neuroendocrinology

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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: 62%

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 Thyroid Status on the Thyrotrophin-Releasing Hormone-Degrading Activity of Rat Serum

Cited by 45 publications

References 11 publications

Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

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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