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  • Author: Xuan-Ping Pang x
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Xuan-Ping Pang, Jerome M. Hershman, Vierka Smith, A. Eugene Pekary and Masahiro Sugawara


Previous work showed that treatment of rats with tumour necrosis factor-α produced a model of nonthyroid illness in which there was reduction of circulating thyroid hormones and TSH, reduced thyroid response to TSH, and reduced thyroid iodide uptake. In vitro studies showed that tumour necrosis factor-α binds to a specific receptor on FRTL-5 rat thyroid cells, that TSH increases the number of tumour necrosis factor-α receptors, and that tumour necrosis factor-α inhibits iodide uptake by these cells. In the present study, we obtained additional data on the effects of tumour necrosis factor-α on FRTL-5 cells and studied the mechanism of action of tumour necrosis factor-α in these cells. Tumour necrosis factor-α inhibited both basal and TSH-stimulated [125I]iodide uptake; tumour necrosis factor-α slowed the recovery of [125I]iodide trapping after the cells were exposed to TSH and augmented the loss of the [125I]iodide trapping function after the cells were deprived of TSH; tumour necrosis factor-α inhibited [125I]iodide trapping in a noncompetitive manner; tumour necrosis factor-α did not affect cell growth of FRTL-5 cells. Interleukin-1 (IL-1) also inhibited basal and TSH-stimulated [125I]iodide uptake, but it stimulated cell growth. Tumour necrosis factor-α and IL-1 did not affect the generation of cAMP in the presence or absence of TSH; these cytokines blocked the cAMP-induced stimulation of [125I]iodide uptake. Tumour necrosis factor-α did not affect [3H]arachidonic acid uptake or release by FRTL-5 cells. The inhibitors of the phospholipase A2-arachidonic acid pathway did not affect the action of tumour necrosis factor-α. The H2O2 scavenger, catalase, did not block the action of tumour necrosis factor-α. The results show that both tumour necrosis factor-α and IL-1 inhibit FRTL-5 function and that the site of action of these cytokines is distal to the production of cAMP. The actions of tumour necrosis factor-α on FRTL-5 cells do not appear to be mediated by the phospholipase A2-arachidonic acid pathway or by H2O2.

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Xuan-Ping Pang, An Ouyang, Tian-Sue Su and Jerome M. Hershman

Abstract. Endemic goitre and cretinism are still a public health problem in China. An epidemiological survey showed that about 5% of the inhabitants in Daxin village, Henan province, had goitre or cretinism after an iodized salt prevention programme had been carried out for two decades. The main food for the inhabitants of this area has an iodine content <30 nmol/kg and the water for cooking and drinking has an iodine concentration between 7–12 nmol/l. We studied thyroid function in subjects of this village. There were 42 with grade 0 goitre (males 29, females 13), 42 grade I (males 23, females 19), 27 grade II (males 9, females 18), 31 grade III (males 14, females 17) and 34 cretinism patients (males 30, females 4) diagnosed and classified according to WHO criteria. Serum T4, free T4, T3, free T3, T3 uptake, TSH and thyroglobulin were measured in these subjects. The patients with goitre or cretinism had significantly decreased serum free T4 and increased serum T3 and free T3 levels compared with those of controls. Thyroid size was positively correlated with age and serum thyroglobulin concentrations. Serum thyroglobulin was significantly increased even in the grade 0 goitre subjects. The percentages of subjects with serum free T4 < 12 nmol/l, T3 >2.5 nmol/l, free T3 >5.2 pmol/l, TSH >3.5 mU/l, T3/T4 ratio >0.03 and free T3/free T4 ratio >0.36 were significantly higher among goitre and cretinism patients than among controls. The data suggest that there is partial compensation for a marginal deficiency of iodine in the inhabitants of this village.

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Masayoshi Yoshimura, A Eugene Pekary, Xuan-Ping Pang, Loretta Berg, Laurence A Cole, Andrew Kardana and Jerome M Hershman

Yoshimura M, Pekary AE, Pang X-P, Berg L, Cole LA, Kardana A, Hershman JM. Effect of peptide nicking in the human chorionic gonadotropin β-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors. Eur J Endocrinol 1994;130:92–6. ISSN 0804–4643

It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid-stimulating activity. Heterologous forms of the hCG molecule occur in the purified preparations extracted from urine of pregnant women and patients with trophoblastic diseases. This work was undertaken to determine the effect of peptide nicking in the hCG-β subunit on its thyrotropic potency. Using Chinese hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH) receptors, we examined the effect of nicked hCG on cyclic AMP (cAMP) production and receptor binding. The effect of human leukocyte elastase (hLE), a nicking enzyme, on standard hCG also was examined in the cAMP assay and on receptor binding. We studied five hCG preparations extracted from the urine of normal pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two preparations (C2, 96% nicked and M4, 100% nicked in the β44–49 region) showed about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the same region. Non-nicked hCG (P8) had the weakest potency among all of the samples tested. Treatment of standard hCG with hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost identical. We have confirmed the increased in vitro thyrotropic activity of hCG nicked in the β-intercysteine loop on recombinant human TSH receptors. These data suggest that peptide heterogeneity of the hCG molecule may modulate the in vivo thyrotropic activity of hCG in pregnant women and patients with trophoblastic diseases.

Jerome M Hershman, Endocrinology-W111D, West Los Angeles VA Medical Center, Los Angeles, California 90073, USA