BACKGROUND: Although there have been some case reports suggesting that bone in patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone (PTH), no information is available as to whether serum PTH concentration is related to bone metabolic markers or to bone mineral density (BMD) in PHP. OBJECTIVE: To address these relationships, by comparing intact serum PTH, bone metabolic markers and BMD in patients with PHP with those in patients with idiopathic hypoparathyroidism (IHP) and postoperative hypoparathyroidism (OHP). METHODS: Intact serum PTH, bone metabolic markers (osteocalcin, tartrate-resistant acid phosphatase, pyridinoline, deoxypyridinoline) and BMD by dual-energy X-ray absorptiometry or single-photon absorptiometry were measured in patients with PHP Ia (n=2) and PHP Ib (n=8). The results were compared with those in patients with IHP (n=5) and OHP (n=14). RESULTS: All bone metabolic markers measured were present in significantly greater amounts in patients with PHP Ib than in those with IHP+OHP. The Z score (standard deviation of average BMD at each age) of the BMD of femoral neck was significantly lower in patients with PHP Ib than in those with IHP+OHP. The Z scores of BMD of lumbar spine and radius were also lower in patients with PHP Ib than in those with IHP+OHP, but the difference was not significant. Moreover, the intact serum PTH concentrations were significantly and positively related to bone metabolic marker levels in all patients, and the intact serum PTH concentrations were significantly and negatively related to BMD of lumbar spine in PHP patients. CONCLUSIONS: These results suggest that PTH stimulates bone turnover in PHP Ib patients, resulting in a relatively lower BMD in PHP Ib patients than in IHP+OHP patients. The present study indicates that bones of most cases of PHP could respond to PTH.
M Kanatani, T Sugimoto, H Kaji, K Ikeda and K Chihara
T. Suzuki, R. Higashi, T. Hirose, H. Ikeda and K. Tamura
Conscious dogs were infused intravenously with ethanol in doses of 0.7 and 1.0 g/kg. The adrenal venous blood samples were collected before and after the infusion of ethanol and analysed for 17-hydroxycorticosteroids (17-OHCS). After the infusion of 0.7 g/kg (subanaesthetic dose) of ethanol the adrenal 17-OHCS secretion rate showed either a slight increase or no change. After the infusion of 1.0 g/kg (anaesthetic dose) of ethanol the adrenal 17-OHCS secretion rate increased markedly and reached 1.21±0.15 (mean±sem) μg/kg/min, while it was 0.09±0.023 μg/kg/min before the infusion.
K Ejima, H Nanri, M Araki, K Uchida, M Kashimura and M Ikeda
OBJECTIVE: To examine whether or not estrogens induced the expression of protein thiol/disulfide oxidoreductases such as protein disulfide isomerase (PDI), thioredoxin (Trx), Trx reductase, and glutaredoxin (Grx) in vascular endothelial cells. METHODS: The regenerative effects of the protein thiol/disulfide oxidoreductases, PDI, Trx and Grx, on oxidatively damaged proteins were assayed using H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reporter enzyme. The induction of protein thiol/disulfide oxidoreductases and the accumulation of protein adducts generated by lipid peroxidation were examined by Western blotting in estrogen-treated bovine aortic endothelial cells (BAECs). RESULTS: Reduced PDI, Trx and Grx regenerated the H2O2-inactivated GAPDH in vitro. The levels of these protein disulfide oxidoreductases in BAECs were increased by pretreatment with 0.01-10 micromol/l 17beta-estradiol, the largest increase (about fourfold of the control) being found for PDI. Other sex hormones such as progesterone and testosterone did not affect the contents of these oxidoreductases in BAECs. 4-Hydroxy-2-nonenal (HNE)-protein adducts, which are generated by lipid peroxidation, were accumulated in BAECs exposed to paraquat, whereas the pretreatment of BAECs with 17beta-estradiol suppressed their accumulation. CONCLUSIONS: The estrogen-mediated induction of the protein thiol/disulfide oxidoreductases such as PDI, Trx, Trx reductase and Grx suggested a possible involvement of these oxidoreductases in the antioxidant protection of estrogen observed in the vascular system.
S. C. Chiu, K. Kubota, N. Kuzuya, H. Ikeda, H. Uchimura and S. Nagataki
Abstract. Mice were injected sc with TSH (0.5 U) at 12 h intervals for 5 days. Groups of mice were sacrificed daily to determine serum T4 and T3 concentrations, 4 h thyroidal 125I uptake, distribution of 125I among thyroidal iodoamino acids, and thyroidal content of T4 and T3. Serum T4 and T3 concentrations increased significantly after the initial injection of TSH and gradually decreased thereafter, reaching initial levels on the 3rd and 4th days, respectively. In contrast to serum hormone levels, thyroidal 125I uptake, incorporation of 125I into T4 and T3 increased significantly on the first day and remained elevated throughout the period of TSH-treatment. Thyroidal T4 content expressed as μg/mg weight of tissue decreased significantly on the first day and thereafter remained constant. Thyroidal T3 content did not change significantly throughout the experimental period. The differences between thyroidal synthesis and thyroidal contents of T4 and T3 strongly suggest that thyroid hormone secretion is being continuously stimulated. Transient increases in serum T4 and T3 concentrations are probably due to a gradual increase in the rate of peripheral degradation of thyroid hormones. These results suggest that TSH-induced refractoriness in thyroidal iodine metabolism does not appear to exist, at least when TSH is given in vivo for 5 days.
Y Furuhata, R Kagaya, K Hirabayashi, A Ikeda, KT Chang, M Nishihara and M Takahashi
BACKGROUND: Human growth hormone (hGH) transgenic (TG) rats have been produced in our laboratory. These TG rats are characterized by low circulating hGH levels, virtually no endogenous rGH secretion, and massive obesity. OBJECTIVE: To elucidate how energy balance and leptin sensitivity contributed to the establishment of this obesity. DESIGN AND METHODS: Food intake, locomotor activity and leptin concentrations in serum and cerebrospinal fluid were measured in TG rats and their non-transgenic littermates (control). The effect of intraperitoneal and intracerebroventricular injection of leptin on food intake and body weight gain was also examined. RESULTS: An increase in food intake and a decrease in locomotor activity were observed from 4 and 7 weeks of age, respectively, in the transgenic rats compared with control. Serum leptin concentrations of the transgenic rats were more than twice as high as those of control rats and were associated with an increased white adipose tissue mass and ob gene expression. Intraperitoneal injection of leptin significantly decreased food intake and body weight gain in control rats, but not in transgenic rats. Leptin concentration in the cerebrospinal fluid of transgenic rats was not different from that of control rats, and intracerebroventricular injection of leptin was similarly effective in reducing food intake and body weight gain as it was in control rats. CONCLUSIONS: These results suggest that the transgenic rats, whose GH secretion is suppressed, develop obesity due to early onset of an increase in food intake and a decrease in locomotor activity with leptin resistance resulting from deteriorating leptin transport from peripheral blood to cerebrospinal fluid.
N Koriyama, M Nakazaki, H Hashiguchi, K Aso, Y Ikeda, T Kimura, H Eto, H Hirano, S Nakano and C Tei
OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.