Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 47 , Issue 4
Showing 1-16 articles out of 16 articles from the selected issue
  • TOSHIYASU SASAOKA, MASASHI KOBAYASHI
    2000 Volume 47 Issue 4 Pages 373-381
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    Shc is composed of 46-, 52-, 66-kDa isoforms which arise from alternative splicing of the primary Shc transcript. Upon insulin stimulation, the activated insulin receptor interacts with Shc. The NPXY motif around 960-Tyr residue of the insulin receptor binds to the N-terminal PTB domain of Shc. Subsequently, the 52-kDa, and, to a lesser extent, the 46-kDa Shc isoforms are tyrosine phosphorylated. Although Tyr-239/240 and Tyr-317 residues are the possible candidates of Shc phosphorylation sites, insulin predominantly phosphorylates the Shc Tyr-317 residue. Phosphorylated Shc binds to Grb2 which forms a complex with Sos guanine nucleotide exchange factor for p21ras. Both tyrosine-phosphorylated Shc and IRS can bind to Grb2, but Shc•Grb2•Sos is the predominant coupling pathway from the activated insulin receptor to p21ras. Along this line, microinjection of anti-Shc antibody inhibited insulin-induced mitogenesis, and the guanine nucleotide exchange activity for p21ras is tightly associated with Shc, but not with IRS. On the other hand, insulin only transiently activates p21ras for the strict hormonal regulation. For this regulation, longer time of insulin treatment deactivates p21ras by dissociation of Sos from the Shc•Grb2•Sos complex while Shc is still complexed with Grb2. Thus, Shc plays a critical role in insulin-induced mitogenesis through regulation of p21ras activity. As regards the impact of Shc on the metabolic aspects, Shc is shown to compete with IRS as the substrate of the insulin receptor. Thus, IRS mediated downstream signaling leading to glycogen synthesis was decreased by overexpression of Shc. Taken together, Shc appears to play an important role in insulin induced mitogenesis, whereas Shc may not be required for regulation of the metabolic aspects of insulin.
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  • BEGOÑA MAESTRO, JAVIER CAMPIÓN, NORMA DÁVILA, CON ...
    2000 Volume 47 Issue 4 Pages 383-391
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    In the present work, we demonstrate that treatment with 1, 25-dihydroxyvitamin D3 for 24 hours increased n a dose-dependent manner the levels of the two major insulin receptor (IR) mRNAs (11 and 8.5Kb) present in U-937 human promonocytic cells. These levels reached maximum values (1.8-fold 11Kb; 1.4-fold 8.5Kb) with the addition of 10-8M 1, 25-dihydroxyvitamin D3. In these optimal conditions the stimulatory effect of 1, 25-dihydroxyvitamin D3 was accompanied by increases in both IR capacity, and insulin responsiveness for glucose transport in these cells. Moreover, such increases appear to be mediated by an enhanced expression of the receptor for 1, 25-dihydroxyvitamin D3, measured at the level of both RNA and protein. These results provide evidence of 1, 25-dihydroxyvitamin D3 acting as genomic stimulator of the insulin response in the control of glucose transport.
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  • A Case Report
    HIROSHI IWAI, YASUHIRO OHNO, MADOKA HOSHIRO, MIKA FUJIMOTO, AKIYOSHI N ...
    2000 Volume 47 Issue 4 Pages 393-399
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    We report a case of a seventy-year-old woman with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and adrenal insufficiency induced by Rathke's cleft cyst. She experienced nausea, vomiting, diarrhea, and headache and disturbance of consciousness induced by hyponatremia at a serum sodium level of 100mEq/l. In spite of severe hyponatremia, urinary sodium excretion was not suppressed and serum osmolality (270mOsm/kg) was lower than urine osmolality (304mOsm/kg), and arginine vasopressin (AVP) remained within normal range. SIADH was diagnosed because she was free from other diseases known to cause hyponatremia such as dehydration, cardiac dysfunction, liver dysfunction, renal dysfunction, hypothyroidism, and adrenal insufficiency. Cranial computed tomographic (CT) scan and cranial magnetic resonance (MR) imaging showed a cystic lesion of approximately 2cm in diameter in the pituitary gland. These images suggested that the cystic lesion was a Rathke's cleft cyst, which was the cause of SIADH. Water restriction therapy normalized her serum sodium concentration and improved her symptoms. After one year, she suffered from general fatigue, appetite loss, fever, and body weight loss (5kg/2 months). She had neither hypotension nor hypoglycemia, but her serum sodium level was low and serum cortisol, ACTH, and urine free cortisol were very low. Therefore, secondary adrenal insufficiency was suspected and diagnosed by stimulation tests. After start of hydrocortisone replacement therapy (10mg/day), her symptoms disappeared. In conclusion, Rathke's cleft cyst should be kept in mind as a potential cause in a patient with SIADH, hypopituitarism, and/or adrenal insufficiency.
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  • SHUO-CHI CHOU, JEN-DER LIN
    2000 Volume 47 Issue 4 Pages 401-406
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    Ketoconazole is an imidazole derivative used to treat systemic and superficial mycoses by inhibiting sterol synthesis in fungi. The drug impairs steroid hormone synthesis by blocking mitochondrial P450-dependent enzyme systems. Because of its potent inhibitory effects on adrenal steroidogenesis, ketoconazole is valuable in controlling hypercortisolism. We investigated the effects of long-term treatment of this drug on three patients who had residual or recurrent Cushing's disease after surgical treatment. Ketoconazole was administered orally and adjusted according to individual response and 24-hour urinary free cortisol excretion levels. All three patients had good clinical and biochemical responses to ketoconazole therapy without adverse effects. The 24-hour urinary free cortisol levels were kept around 114.8±52.4μg/24h, 143.0±59.9μg/24h, and 122.9±79.9μg/24h, respectively (reference range, 35 to 120μg/24h). All three patients had follow-up magnetic resonance imaging or computed tomography of the pituitary gland, which revealed no significant changes in the sellar region. Daily ketoconazole doses ranged from 200 to 1200mg per day. Follow-up periods were 65, 86, and 83 months, respectively. In conclusion, ketoconazole is valuable in the long-term treatment of residual or recurrent Cushing's disease when surgical treatment is contraindicated or unsuccessful.
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  • TAKASHI KIKUCHI, SHIGEKI YABE, TSUGIYASU KANDA, ISAO KOBAYASHI
    2000 Volume 47 Issue 4 Pages 407-416
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    Our previous reports showed detection of antipituitary antibodies (APA) by immunoblot analysis and enzyme linked immunosorbent assay (ELISA) by using rat pituitary tissue as antigen in patients with certain endocrine disorders. In the present report, we evaluated APA by using our immunoblot and ELISA technique in 76 patients with various pituitary disorders. The prevalence of a 22kDa band of APA detected by immunoblot was found to be significantly higher (P<0.01) in patients with pituitary disorders (20 of 76, 26% than in the controls (3 of 209, 1%). APA levels detected by ELISA were significantly higher in patients with GH deficiency, isolated ACTH deficiency, acromegaly, and idiopathic panhypopituitarism compared with control (mean±SD; 2.40±2.66, 2.36±1.87), 2.09±1.87, 3.10±1.96 versus 1.42±0.64 (C.I.) P<0.05, respectively). APA levels detected by ELISA in 7 patients with GH deficiency showed a statistically significant decrease (p<0.05) after administration of GH replacement therapy. APA detection by immunoblot is useful in examining as pathogenesis, while ELISA may be useful as an objective index of pathological state in patients with autoimmune-related pituitary disorders.
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  • RENGASAMY R. MANI MARAN, JAGADEESAN ARUNAKARAN, MARIA M. ARULDHAS
    2000 Volume 47 Issue 4 Pages 417-428
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    The effect of T3 on basal and LH mediated synthesis and secretion of testosterone and oestradiol by puberal rat Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1×103) were cultured for 48 hours at 34°C in a medium containing a range of 5-400ng/mL concentration of T3 or ovine LH after 24 hours initial culture at 37°C. T3 increased testosterone and oestradiol secretions in a dose dependent manner which reached the saturation point with 50ng dose. While the minimum effective dose of T3 (25ng) potentiated the stimulatory effect of the minimum effective dose of LH (25ng) on testosterone secretion, it suppressed the effect of the saturation dose of LH (100ng). Fifty ng T3 quelled the stimulatory effect of either dose of LH. Both doses of T3 increased oestradiol secretion, irrespective of the dose of LH. Addition of androstenedione (500ng/mL) to the culture medium enhanced 25ng T3 induced testosterone and oestradiol secretions. While androstenedione potentiated the stimulatory effect of T3 (25ng) on LH (25ng) induced testosterone and oestradiol secretions, it reversed the inhibitory effect of 50ng T3 on LH mediated testosterone secretion which was accompanied by a decrease in oestradiol secretion. Puromycin (35μg/mL) suppressed the stimulatory effect of T3 on basal and LH mediated testosterone and oestradiol production. Taken together, the present results indicate a direct stimulatory effects of T3 on basal production of testosterone and oestradiol by Leydig cells and its modulatory effect on LH mediated steroidogenic activity varies depending upon the intensity of LH stimuli.
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  • Involvement in Aldosterone Release
    SEIJI MURO, ISSEI TANAKA, TAKESHI USUI, MASATO KOTANI, SHIGEKI KOIDE, ...
    2000 Volume 47 Issue 4 Pages 429-436
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    We examined the role of prostaglandin (PG) E receptors in the secretion of aldosterone. PGE2 is known to exert its various biological functions by binding to PGE receptors. There are four subtypes of PGE receptors, EP1, EP2, EP3, and EP4. Among the PGE receptors EP2 and EP4 subtypes are coupled to Gs protein and stimulate adenylyl cyclase. In this study, PGE2 caused a dose-dependent increase in aldosterone production from the rat adrenal zona glomerulosa cells in vitro accompanied with an increase in intracellular cAMP concentration. A specific agonist for EP2, butaprost, did not increase the cAMP production or the aldosterone release, suggesting the possibility that EP4 mediates the secretion of aldosterone by PGE2. Northern blot hybridization analysis disclosed that EP4 gene was expressed in the rat adrenal gland but that EP2 gene was not. In situ hybridization revealed that EP4 mRNA is present abundantly in the zona glomerulosa of rat adrenal gland. These findings suggest that the PGE2-EP4 system is involved in the regulation of aldosterone secretion from the rat adrenal gland.
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  • A Case Report
    SHINICHI TENO, YUKO NAKAJIMA-UTO, KAZUTAKA NAGAI, MADOKA SHIMIZU-SAITO ...
    2000 Volume 47 Issue 4 Pages 437-442
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    Gastrectomy or vagotomy may result in reactive hypoglycemia, which, in some cases, can reduce the plasma glucose levels to 30-40mg/dl due to rapid digestion and absorption of food, especially carbohydrates. It also occurs sometimes in patients on hemodialysis, where it is a potentially lethal complication. Because insulin has a longer half-life due to lack of renal degradation, hypoglycemia can be induced by insulin in patients with renal failure. We treated a patient with frequent episodes of severe hypoglycemia, that were sometimes accompanied by convulsions. He had undergone total gastrectomy 8 years before and had been maintained on hemodialysis for 3 years. Hyperinsulinemia caused by oxyhyperglycemia associated with post-gastrectomy led to severe hypoglycemia in this patient because of the lack of renal insulin degradation. Since nutritional treatment did not successfully manage his reactive hypoglycemia, an α-glucosidase inhibitor, acarbose, was administered to treat his oxyhyperglycemia. This therapy was very effective and he has not had any recurrence of reactive hypoglycemia since the initiation of the therapy.
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  • Report of Two Cases and Review of the Literature
    MASAAKI MORIOKA, TATSUYA KOBAYASHI, ATSUSHI SONE, YOJI FURUKAWA, HIROY ...
    2000 Volume 47 Issue 4 Pages 443-449
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    Unilateral adrenal hyperplasia (UAH) is a rare, surgically correctable subset of primary aldosteronism (PA), which shows similar endocrine features to aldosterone-producing adenoma (APA). We report here two Japanese patients with UAH. Case 1 was a 62-year-old man with a four-year history of hypertension. Hypokalemia and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed, while no adrenal nodules were identified by abdominal computed tomographic (CT) scan. Adrenal scintigraphy did not reveal definite localization. The selective adrenal-vein sampling for determinations of PAC showed an over-functioning left adrenal gland, and a left adrenalectomy was performed. Diffuse micronodular adrenocortical hyperplasia was observed. Case 2 was a 61-year-old man with a six-year history of hypertension. At the first visit to our hospital, hypokalemia and suppressed PRA with elevated PAC were observed. An abdominal CT scan showed a left adrenal mass 1.5cm in diameter, while adrenal scintigraphy did not reveal definite laterality. A left adrenalectomy was performed, and three macronodules and diffuse micronodular adrenocortical hyperplasia were observed. Hypokalemia, hypertension and endocrine data became normal, and both patients have been well with no signs of recurrence for eight years (case 1) and seven months (case 2) after surgery. Clinical characteristics and endocrine features of UAH are also reviewed.
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  • FANGXIONG SHI, KEIJI MOCHIDA, OSAMU SUZUKI, JUNICHIRO MATSUDA, ATSUO O ...
    2000 Volume 47 Issue 4 Pages 451-459
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    Embryo recovery and subsequent embryonic development from guinea pigs treated with or without Inhibin vaccines were compared to determine the effect of active immunization against the inhibin α-subunit. Twenty female guinea pigs of the Hartley strain were injected 3 times either with 1ml inhibin vaccine (recombinant ovine inhibin α-subunit in oil emulsion: 50μg/ml, inhibin-immunized group), or 1ml placebo (saline in oil emulsion; control group) at 4 week intervals. After one estrous cycle following the last injection, females were naturally mated and embryos were collected at 11:00hr of day 6 of pregnancy (Day 1: sperm in the vaginal smear) for culture in vitro. Active immunization increased the number of corpora lutea (12.6±3.0 vs. 4.6±0.2, P<0.05), recovered embryos (9.8±1.9 vs. 3.6±0.4, P<0.01) and normal embryos (7.8±1.4 vs. 3.6±0.4, P<0.05), although estrous cycle length was not affected (P>0.05). During subsequent 8 day culture in vitro, most of the recovered embryos formed trophoblast outgrowth; 100% (14/14) and 88.2% (15/17) in control and immunized groups, respectively. High levels of inhibin antibody titers were sustained in the Inhibin-immunized guinea pigs at least for 5 months after the last injection while no antibody titer was detected in the control animals. These results indicate that active immunization against the inhibin α-subunit is a long-acting and efficient method to induce superovulation with normal embryonic development in the guinea pig.
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  • HIROMASA KOBAYASHI, TAKESHI USUI, JUNICHI FUKATA, TAKAAKI YOSHIMASA, Y ...
    2000 Volume 47 Issue 4 Pages 461-466
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    While the mechanisms of tumorigenesis for adrenocortical neoplasms remain unknown, several genes, such as Gsα, ACTH receptor (MC2-R), p53, and p16 tumor suppressor genes, are considered to be candidates for adrenocortical neoplasms. Mutation analysis studies have documented these genes in adrenocortical neoplasms, but these studies focused on the mutation of only one of these genes. In the present study we examined the mutations of three of these genes (Gsα, MC2-R, and p53) in adrenocortical neoplasms in Japanese patients. We amplified these genes using polymerase chain reaction and directly sequenced them in 30 functioning adrenocortical neoplasms. As for Gsα, we identified a heterogeneous substitution of glutamine to histidine at codon 227 and a gain of an Nru I restriction endonuclease site. The mutation was restricted to adenomatous tissue, and did not occur in the adjacent normal adrenal tissue or leukocytes of the patient. We did not find any mutations in MC2-R and p53. In conclusion, although the contribution of these three genes to adrenocortical tumorigenesis remains to be determined, it is suggested that the mutation of Gsα might play a role in functional adrenocortical neoplasms.
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  • SHIGEKI MORITA, YASUO UEDA, KATSUMI EGUCHI
    2000 Volume 47 Issue 4 Pages 467-470
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    We report a case of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis induced by propylthiouracil (PTU), and review the literature concerning to anti-thyroid drug-induced ANCA-associated vasculitis. A 45-year-old man treated with PTU developed fever and arthralgia without pulmonary, skin or eye involvement. These symptoms persisted for a long period without specific symptom, sign or laboratory data of other arthritis. Laboratory findings of urine and blood were normal, except for positive MPO-ANCA (191EU) and PR3-ANCA (37EU) findings. After PTU was discontinued without steroids or immune modulating drugs, both symptoms disappeared. Our patient had a high titer of MPO-ANCA. Moreover, titers of ANCA fell in correlation with the course of symptoms after the cessation of PTU, and we diagnosed PTU-induced ANCA-associated vasculitis. Most patients with pulmonary renal syndrome receive anti-thyroid drugs over a prolonged period, but the duration of our case was shorter than those of these patients. It is suggested that our patient was diagnosed at an early stage of ANCA-associated vasculitis before the start of pulmonary or renal involvement.
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  • MELIH AKTAN, REFIK TANAKOL, MELIHA NALÇACI, GÜNÇAG ...
    2000 Volume 47 Issue 4 Pages 471-473
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    It is well known that growth hormone (GH) therapy is associated with increased risk of development of malignant tumors, especially leukemia. In the case presented, growth hormone treatment was initiated in a 25-year-old patient with hypopituitarism. After 4 months of therapy with thrice a week injections of rhGH, acute myelogenous leukemia developed. It was thought that no clearcut evidence existed to establish a relationship between the growth hormone treatment and development of acute leukemia.
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  • BISHONGA CHRISTOPHER
    2000 Volume 47 Issue 4 Pages 475-480
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    In each estrous cycle not all follicles recruited grow to ovulate, as some degenerate through the process of atresia. Apoptosis is the mechanism underlying follicle atresia. TGF-β1 has been implicated in the induction and promotion of apoptosis in many cell types and it is expressed in the ovary. In this study immunohistochemistry was used to localize TGF-β1 in order to correlate the growth factor expression with morphological follicular atresia during diestrus in mice. Small and medium sized follicles had no staining for TGF-β1 in the granulosa or theca cell layer. Weak to moderate TGF-β1 expression was present in the theca cells of both large healthy and atretic antral follicles. Large healthy antral follicles showed weak granulosa staining but this was not observed in atretic follicles. Strong TGF-β1 staining was present in the interstitial, corpus luteum and oocytes of all follicle stages. These results suggest that in the mouse TGF-β1 promote follicular growth and differentiation rather than follicular atresia.
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  • YOSHIYUKI BAN, YOSHIO BAN, MATSUO TANIYAMA, HIDEO HARA, TAKUMI ABE, TA ...
    2000 Volume 47 Issue 4 Pages 481-486
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    We report a patient with primary hypothyroidism associated with an aberrant ACTH response to the LH-RH test. A 40-year-old woman was admitted to our hospital displaying headache, nausea, and numbness on the left side of her face, upper limbs, and tips of her toes. Computed tomography and magnetic resonance imaging revealed a mass-like lesion in the pituitary. A high serum TSH concentration with concomitant low thyroid hormone concentrations resulted in a diagnosis of primary hypothyroidism. To exclude the possibility of a coexisting pituitary tumor including a TSH-secreting tumor, we performed dynamic TSH secretion tests. TRH testing showed an excessive, delayed TSH response, typical of primary hypothyroidism. Serum TSH decreased not only after administration of CRH, octreotide, or L-DOPA, but also after administration of LH-RH. In this case, LH-RH testing induced ACTH secretion. To determine if aberrant ACTH secretion in response to LH-RH loading is a common phenomenon in severe primary hypothyroidism, we performed the LH-RH test on 4 additional patients with pituitary enlargement due to primary hypothyroidism. Two patients demonstrated aberrant ACTH secretion in response to LH-RH loading, but the others did not. To our knowledge, this is the first report of aberrant LH-RH-stimulated ACTH secretion in primary hypothyroidism.
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  • KAZUKI OHTA, MASAYOSHI SHICHIRI, TOHRU KAMEYA, OSAMU MATSUBARA, TAIHEI ...
    2000 Volume 47 Issue 4 Pages 487-492
    Published: 2000
    Released: November 25, 2006
    JOURNALS FREE ACCESS
    A 26 year-old man with suspected Cushing's disease underwent transsphenoidal exploration of the pituitary without any evidence of microadenoma or hyperplasia. Progressive hypercortisolism necessitated bilateral adrenalectomy. Postoperatively, skin pigmentation gradually developed with a marked elevation of plasma ACTH levels, and CT scanning uncovered a thymic mass. Following removal of the thymic mass, skin pigmentation disappeared and plasma ACTH levels fell to normal. The excised mass was found to be a benign thymic hyperplasia without epithelial or carcinoid tumor cells. However, gel chromatography showed that the thymic tissue extract contained high ACTH content comparable to that of ectopic ACTH-producing tumors with a major component corresponding to ACTH(1-39). Northern blot analysis and in situ hybridization revealed the expression of pro-opiomelanocortin transcripts in lymphocytes of thymic hyperplasia. This report suggests that lymphocytes in thymic hyperplasia are the most likely site of deregulated ACTH expression causing ectopic ACTH syndrome.
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