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71 巻, 5 号
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塩谷 弥兵衛1995 年 71 巻 5 号 p. 647-650
発行日: 1995/07/20
公開日: 2012/09/24
ジャーナル フリーRecent progress in pineal research was briefly reviewed in following 5 research fields.
1. Relationships between the pineal gland and the reproductive system.
2. Innervation of the pineal gland.
3. Neuroactive substances in the pineal gland.
4. Melatonin receptor.
5. Effects of melatonin on blood pressure and body temperature.抄録全体を表示PDF形式でダウンロード (445K) -
諏訪 八大, 藤川 浩, 下平 和久, 大倉 史也, 斎藤 裕, 矢内原 巧1995 年 71 巻 5 号 p. 651-658
発行日: 1995/07/20
公開日: 2012/09/24
ジャーナル フリーBone is known to be a target organ of not only estrogens, but also androgens. The mechanism by which these steroids exert their action on bone cells is still poorly understood. In the present study, the effect of 17β-estradiol (E2) on 5α-reductase activity, converting testosterone (T) to a more potent biological androgen, dihy-drotestosterone (DHT), was assessed in an osteoblast-like cell line of rat origin (UMR106-01). Cells were incubated under standardized conditions with varying concentrations of E2 (10-12-10-6M) for 48 hours. Incubation medium was replaced when the cells were preconfluent and thereafter at 24 hour intervals. Then the cells were harvested. Each cell homogenate was incubated with [4-14C]-T. DHT was detected as a single metabolite on silicagel thin layer chromatography. 5α-reductase activity was determined by measuring the amount of labeled DHT from T. The radiochemical purity of DHT recovered after incubation was confirmed by recrystallization to constant specific activity. Under the conditions used, no estrogen was detected. Production of insuline-like growth factor-I and alkaline phosphatase in UMR106-01 was increased when E2 was added into the culture medium, however, 5α-reductase activity was significantly decreased by the addition of 10-12M to 10-6M of E2. Maximum inhibition was noticed at 10-10M. Our results demonstrate that UMR106-01 cells have a capacity to transform T into the biologically more potent androgen, DHT. The result, that the enzyme activity was influenced by E2, suggests the regulatory mechanism of both sex steroids on the steroid metabolism in osteoblasts.抄録全体を表示PDF形式でダウンロード (752K) -
糖代謝における末梢血中CRHの意義末丸 修三, 末丸 紘三, 西岡 達矢, 橋本 浩三1995 年 71 巻 5 号 p. 659-672
発行日: 1995/07/20
公開日: 2012/09/24
ジャーナル フリーWe present a 66-year-old man with morning fasting hypolgycemia from an unknown cause associated with markedly suppressed levels of insulin. In this patient we examined the diurnal changes of plasma corticotropin-releasing hormone (CRH), ACTH, cortisol, glucose, insulin and body temperature, and the correlations among them. We also discussed an implication of plasma CRH in glucose metabolism by taking these findings together with results from previous studies on plasma CRH in diabetic or hypoglycemic animals and human beings. In this case, the stress induced by severe spontaneous hypoglycemia in the morning fasting state increased CRH in plasma compared to the euglycemia state and simultaneously activated the hypothalamic-pituitary-adrenal system as well as the sympathetic nervous system remarkably. The daily intravenous infusion of glucose brought the fasting hypoglycemia to normal and hypothermia to normothermia in the morning, and improved no or blunt responsiveness of insulin to glucose. On the 50th day of therapy, the i.v. infusion of glucose quickly produced moderate hyperglycemia and an increase in plasma insulin, and inhibited secretions of CRH, ACTH and cortisol. The source of plasma CRH remains obscure. However, the positive correlations of plasma CRH with both plasma ACTH and cortisol and several lines of evidence indicate that CRH in peripheral plasma is derived from both the hypothalamus and extrahypothalamic peripheral tissue and that during stressed conditions, in particular, the CRH increase in plasma is derived mainly from the paraventricular nucleus of the hypothalamus. The role of CRH not only in the systemic circulation but also in the endocrine pancreas for glucose metabolism remains to be clarified.抄録全体を表示PDF形式でダウンロード (1384K) -
富澤 由雄, 佐藤 則之, 清水 弘行, 森 昌朋1995 年 71 巻 5 号 p. 673-678
発行日: 1995/07/20
公開日: 2012/09/24
ジャーナル フリーThe interrelationship between the hypothalamic-pituitary-adrenal axis and the immune system has been becoming clear. However, most research about this interrelationship has been porformed by in vitro experiments and by using animal models. To know the effect of hypercortisolism on human immune systems in vivo, we report at 32-year-old man with typical Cushing disease whose specific and non-specific immunological functions were estimated before and after successful transsphenoidal surgery. We made a diagnosis of Cushing disease with dexamenthasone suppression test, CRF stimulation test, venous sampling, and MRI scan. Before transsphenoidal surgery, both plasma ACTH (100pg/ml) and urinary free cortisol (567μg/day) were higher than the normal range, and the parameters of specific (CD4/CD8 ratio, serum Ig A, PHA/Con-A induced T cell blast formation, and NK cell activity) and non-specific (neutrophil phagocytosis and bactericidal function) immunological functions were clearly impaired. However, at 6 weeks and 6 months after the tumor excision when hormonal abnormalities were changed to normal, every impaired immunological function was improved to the normal range. These data suggest that impaired specific and non-specific immunological functions were induced by hyercortisolism not only in vitro but also in vivo (a state of Cushing disease).抄録全体を表示PDF形式でダウンロード (648K) -
本間 誠次郎, 竹沢 豊, 山中 英寿1995 年 71 巻 5 号 p. 679-694
発行日: 1995/07/20
公開日: 2012/09/24
ジャーナル フリーTZP-4238 suppresses plasma testosterone in humans, but its action on the androgen biosynthesis pathway has not been established. Therefore, we researched the testicular testosterone level and the testosterone biosynthesis pathway in vitro in rats before and after receiving a single or continuous oral dose of TZP-4238.
The total testosterone fell to 60% of the basal level within 3-8 hr (p<0.05) and then returned to the control concentration by 24 hr after a single administration of 32mg/kg. The alteration of the plasma testosterone level correlated well with that of the intratesticular level, which was decreased to 50% at 3-8 hr and recovered to the control level by 24 hr. However, the decrement of the plasma LH level at 3-8 hr after a single oral administration was slight and it then returned to the original level at 12 hr. During the 8 weeks of daily administration of 0.5 mg/kg of TZP-4238 or chlormadinone acetate to dogs, the plasma testosterone levels were slightly lower than the basal extent.
In vitro experiments were conducted on the rat testis using the exogenous precursor steroids 20α-hydrox-ycholesterol, pregnenolone and progesterone, in various steps leading to the biosynthesis of testosterone. Trilostane acted at 3β-hydroxysteroid dehydrogenase (50% inhibition concentration, IC50 was 1μM), ketoconazole inhibited the 17α-hydroxylase, and C20, 22,-and C17,20-lyase activities, with an IC50 of 1-50μM. Cyproterone acetate inhibited both the 3β-hydroxysteroid dehydrogenase (IC50;50μM) and C17,20-lyase. On the other hand, TZP-4238 exhibited a weaker inhibition of 3β-hydroxysteroid dehydrogenase (IC50;100μM) than cyproterone acetate, but not of hydroxylase and lyase. Though TZP-4238 did not inhibit the increased testosterone level induced by hCG, trilostane markedly inhibited the effect induced by hCG. These in vitro findings confirmed that TZP-4238 has no direct inhibitory effect on testicular steroidogenesis. These findings suggest that TZP-4238 causes a depression in plasma testosterone, and its action appears to be mainly the suppression of pituitary LH secretion.抄録全体を表示PDF形式でダウンロード (1391K) -
池窪 勝治, 日野 恵, 才木 康彦, 梶川 麻里子, 服部 尚樹, 石原 隆, 森寺 邦三郎, 倉八 博之1995 年 71 巻 5 号 p. 695-708
発行日: 1995/07/20
公開日: 2012/09/24
ジャーナル フリーDevelopment and fluctuation of thyroid hormone autoantibody (THAA) titers were observed during long-term treatment of thyroid diseases in three patients.
The presence of THAA was noticed by spuriously high serum free thyroid hormone levels measured with an analog tracer RIA (Amerlex-M FT3, FT4) in all three patients. Amerlex-M FT3 or FT4 levels gradually decreased to appropriate values for the clinical status according to the decreasing titers of THAA.
Free thyroid hormone levels with radiolabeled antibody radioassay (Amerlex-MAB FT3, FT4) were not affected by the THAA and always reflected actual thyroid function.
Case 1 was a 46-year-old man with untreated primary hypothyroidism. Auti-T4 autoantibody was detected in his serum. The 125I-T4 analog binding to the autoantibody (125I-T4 analog binding ratio) gradually declined after L-T4 therapy and finally almost disappeared two years and four months later. Amerlex-MAB FT4 level rose to the normal range two months after T4 therapy, but TSH level remained slightly elevated (5.4-13μU/ml) for five months during T4 therapy. The 125I-T4 analog binding ratio and anti-Tg autoantibody (TgAb) titer were inversely correlated.
Case 2 was a 72-year-old woman had received desiccated thyroid for a long time. Sequential changes of 125I-T4 analog binding ratio were very similar to those of TgAb titer.
Case 3 was a 74-year-old woman with Graves' disease. She had been treated with methimazole (MMI) and desiccated thyroid for three years and five months. Ten months after stopping both drugs, anti-T3 autoantibody was detected. The 125I-T3 analog binding ratio was transiently elevated and gradually declined to reference range for four years during L-T4 therapy. 125I-T3 analog binding ratio and TgAb titer changed in a similar way.
These results suggest that desiccated thyroid hormone therapy and TgAb formation are related to the development of THAA and that L-T4 therapy reduces the THAA titer.抄録全体を表示PDF形式でダウンロード (1146K)
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