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69 巻, 2 号
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岡田 弘二1993 年 69 巻 2 号 p. 67-79
発行日: 1993/02/20
公開日: 2012/09/24
ジャーナル フリーRecently, the action of steroid hormones are interpreted as the results from the interaction with its proper receptors. However, every steroid hormones and steroid drugs have many biological effects, and if one steroid receptor is enough to result in these multiple effects or not is not well known. On the other hand, our experimental results showed that some steroid drugs are metabolized, in vivo, to form several biologically active compounds.
Norethindrone, a representative progestational compound, has also some estrogenic and androgenic effects. It was demonstrated, in our laboratory, that the compound was converted, in vivo, to several androgens and to estrogen, ethynyl estradiol. Since it was demonstrated later that ethynyl estradiol but not norethindrone showed estrogenic activity in vitro, it can be concluded that the estrogenic activity of norethindrone was derived from the metabolite of norethindrone, ethynyl estradiol. Although the chemical structure of norethindrone is far different from that of progesterone, it was demonstrated that the progestational effect of norethindrone was derived from the interaction of norethindrone with progesterone receptor. The binding site of norethindrone with the receptor is identical with that of progesterone. Some steroid drugs, such as lynestrenol are inactive, per se, and the conversion of the compound into norethindrone in liver tissue well explained the progestational activity of the compound. In such cases, the studies on the interaction of original compound with receptor in target tissues will give us poor information on the mechanism of steroid action.
Some progestational compounds such as medroxyprogesterone acetate has anticancer effect, but norethindrone and the related compounds have no such an effect. This indicates that the receptor for anticancer effect is different from the receptor for common progestational effect. This was confirmed by many ways and the receptor for anticancer effect was partially characterized.
Although dydrogesterone is a potent progestational agent and the endometrial response to this compound is almost identical with that to progesterone, it results in neither the elevation of basal body temperature nor an inhibition of obulation, which are commonly observed with other progestogens. This also raises a doubt on the identity of progesterone receptors in peripheral and central tissues.
Mechanism of action of synthetic steroids are very complicated and it must be studied in connection with the chemical structure, the metabolism and steroid receptor interaction.抄録全体を表示PDF形式でダウンロード (996K) -
渡辺 哲子, 阿部 圭志, 角田 一男, 今井 潤, 許 士郎, 村上 治, 吉永 馨, 鈴木 貴, 笹野 公伸1993 年 69 巻 2 号 p. 80-86
発行日: 1993/02/20
公開日: 2012/09/24
ジャーナル フリーA 43-year-old female was admitted to our hospital for high blood pressure control. She showed hypokalemia with increased urinary potassium excretion, high plasma aldosterone concentration (33.9ng/dl, normal range; 2-12ng/dl) and reduced plasma renin activity (trace, normal range; 0.83-5ng/ml/hr).
Bilateral adrenal tumors were revealed by abdominal computed tomography, and left adrenalectomy and right partial adrenalectomy were performed. Cytochromes p-450 and other enzymes involved in aldosterone synthesis were found predominantly in the tumor portions but not in the zona glomerulosa of the attached adrenals, which histopathologically showed paradoxical hyperplasia. This was a rare case of bilateral aldosterone-producing adrenal adenomas, which we could differentiate from idiopathic hyperaldosteronism by employing immunohistochemical analysis of steroidogenic enzymes.抄録全体を表示PDF形式でダウンロード (1364K) -
原 秀雄, 伴 良雄, 佐藤 龍次1993 年 69 巻 2 号 p. 87-92
発行日: 1993/02/20
公開日: 2012/09/24
ジャーナル フリーWe studied serum superoxide dismutase (SOD) in patients with Graves' disease. Measurements of immunoreactive Cu, Zn-SOD and SOD-like activities were made by enzyme-linked immunosorbent assay (Ube Industries Ltd) and Nitroblue Tetrazorium method (Wako Ltd), respectively. Serum from patients with untreated Graves' disease had a significantly higher concentration of Cu, Zn-SOD and higher SOD-like activity than those from normal subjects, patients with Graves' disease under treatment over one year, patients with Graves' disease in remission, and patients with untreated Hashimoto's disease. Methimazole treatment produced no significant change in SOD-like activity and Cu, Zn-SOD concentration when patients with Graves' disease had normal thyroid function.
These results indicated that oxidative tissue injury existed in patients with Graves' disease with normal thyroid function under treatment; however, we could not clearly establish that thyroid function had a direct connection with oxidative tissue injury.抄録全体を表示PDF形式でダウンロード (512K) -
磯部 和正, 中井 利昭1993 年 69 巻 2 号 p. 93-101
発行日: 1993/02/20
公開日: 2012/09/24
ジャーナル フリーATP is ubiquitously present in neural tissues and is released during nerve stimulation. It is known that splanchnic nerve terminals located in adrenal medulla also contain acetylcholine and ATP. These substances may be released concomitantly with nerve stimulation. ATP can exert its effects on neuron-effector junctions by acting directly as a neurotransmitter by increasing or decreasing the release of other neurotransmitters or by modulating their actions.
Chem et al. reported that ATP and adenosine inhibited acetylcholine stimulated secretion of catecholamine from isolated bovine adrenal medullary cells. However, Kim et al. showed that extracellular ATP stimulated catecholamine secretion from cultured bovine adrenal medullary cells. Therefore, we investigated the effect of ATP on second messengers levels in cultured porcine adrenal medullary cells as well as catecholamine release from the cells.
ATP (500μM~5mM) evoked catecholamine release significantly (p<0.05). An unhydrolyzable ATP analogue, ATP γ S, was several times more potent than ATP in the secretion. ATP-evoked maximal secretion of catecholamine was several times less potent than that evoked by carbachol. Removal of extracellular Ca2+ did not effectively inhibit ATP-induced secretion. 45Ca2+ influx was not observed by the addition of ATP. These results indicated that the catecholamine secretion induced by ATP was independent of extracellular Ca2+
ATP evoked cAMP production slightly at 1mM and did not affect cGMP content. On the other hand, ATP (100μ~5mM) induced a remarkable increase in inositol trisphosphate, a messenger for mobilization of Ca2+ from intracellular storage sites. Adenosine (1mM) failed to induce inositol phosphates accumulation and catecholamine release. Thus it seemed that these actions of ATP were evoked via stimulating P2 purinergic receptor.
These results suggest that ATP modulates catecholamine secretion from cultured porcine adrenal chromaffin cells by activating phospholipase C.抄録全体を表示PDF形式でダウンロード (835K) -
石原 理, 飯野 好明, 斎藤 正博, 関 博之, 木下 勝之1993 年 69 巻 2 号 p. 102-108
発行日: 1993/02/20
公開日: 2012/09/24
ジャーナル フリーIn an attempt to induce ovulation in Clomiphene resistant secondary amenorrhoea patients, the gonadotrophin-releasing hormone agonist (Buserelin)(600-900μg/day) was administered in 13 cases aged 18 to 24 years for one week from day 5 of the menstrual cycle. Serum levels of luteinizing hormone increased in all patients, and estradiol levels increased in 10 of 13 patients in response to Buserelin. However, ovulation was observed in 6 cases, and the response to Clomiphene was recovered in all of these 6 cases in their subsequent menstrual cycles. These results imply the existence of a subgroup who respond to Buserelin in Clomiphene resistant secondary amenorrhoea patients and a possible new approach for the treatment of secondary amenorrhoea.抄録全体を表示PDF形式でダウンロード (565K)
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