PubMed Health⌕ Search

Biomedical subjects

R Takayanagi

Publications and source records attributed to R Takayanagi.

At least 19 recordsLinked to original sources
PubMed1995

cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line.

A human T lymphoid cell line, PEER, dies by apoptosis in the presence of PMA and calcium ionophore. A new gene, TINUR, was cloned from apoptotic PEER cells. The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex. TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor. TINUR binds to the same DNA sequence as NGFI-B/nur77. We also propose that the NGFI-B/nur77 family can be classified into two subtypes.

Amino Acid Sequence↗
PubMed1995

[A case of primary hypothyroidism with pituitary enlargement and abnormal secretion of growth hormone and prolactin].

A case of primary hypothyroidism accompanied by pituitary enlargement and pituitary dysfunction is documented. A 27-year-old woman was admitted to our hospital for further examination of pituitary enlargement. Endocrinological examination revealed that she had primary hypothyroidism. Her TSH level in serum was elevated to more than 300 microU/ml. She also had pituitary dysfunction such as hypersecretion of prolactin in response to TRH and paradoxical rise of GH to glucose load. Serum antibodies against the pituitary gland were negative. Magnetic resonance imaging (MRI) examination showed an enlarged pituitary gland extending to supraseller cistern, which was homogeneously enhanced after Gadolinium-DTPA treatment. Treatment with 50-100 micrograms of levothyroxine sodium normalized her thyroid function and secretion of GH and prolactin. In addition, periodic MRI examination demonstrated a gradual decrease in the size of the pituitary gland after the treatment. The above clinical course indicates that pituitary enlargement in this patient occurred as a result of primary hypothyroidism. The mechanism of the abnormal secretion of TSH, GH and prolactin secondary to primary hypothyroidism was discussed.

Adult↗
PubMed1995

Type 1 angiotensin II receptors of adrenal tumors.

The present study was designed to clarify the transcriptional regulation of the human type 1 angiotensin II receptor (AT1) gene and its pathophysiological roles in steroidogenesis by adrenal tumors. A cDNA encoding type 1 angiotensin II receptor (AT1) was isolated from a human liver cDNA library encoding a protein of 359 amino acids with seven transmembrane segments. It is very likely that human has only one type of AT1 receptor, in contrast with rodents. A genomic clone containing 217 bp of exon 1 and 2558 bp of the 5'-flanking region of human AT1 receptor gene was isolated. Its proximal promoter region contained putative TATA and GC boxes, CRE and AP1 sites. Aldosterone-producing adenoma (APA) contained significantly higher levels of mRNA for AT1 and ACTH receptors than normal tissues adjacent to APA. There were no mutations within the cytoplasmic third loops of AT1 and ACTH receptors in APAs examined. APA showed increased expression of the mRNA for P450c11 and decreased expression of the mRNA for P450c17. These results suggest that renin-independent overproduction and clinically observed ACTH-dependent production of aldosterone in APAs may results from the enhanced transcription of P450c11 and ACTH receptor genes. The mechanism of the discordantly increased expression of AT1 receptor in APA remains to be clarified.

Adenoma↗
PubMed1995

Aromatase in bone cell: association with osteoporosis in postmenopausal women.

To clarify the possible action of adrenal androgen on bone cell, the existence, characteristics and regulation of aromatase in human osteoblast-like osteosarcoma cells (HOS) and primary cultured osteoblast-like cells from normal human bones (HO) were examined in this study. Significant positive correlation between bone mineral density (BMD) and serum dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopausal women (51-99 years old) but no correlation was seen between BMD and serum estradiol (E2). In subset analysis, strongly positive correlation of serum DHEA-S and estrone (E1) with BMD was observed in postmenopausal women aged less than 69 years old. Administration of DHEA to ovariectomized rat significantly increased BMD and decreased relative osteoid volume in femur. These in vivo findings strongly suggested that serum adrenal androgen may be converted to estrogen in peripheral organ, especially, osteoblast and be important steroids to maintain BMD. [3H]DHEA was converted to [3H]androstenedione and [3H]androstenedione to [3H]estrone in primary cultured human osteoblast. Osteoblast-like cells showed aromatase activity, and an apparent Km and the Vmax were 4.74 +/- 0.78 nM (mean +/- SD, n = 3) and 0.83 +/- 0.79 fmol/mg protein/h for HOS, and 4.6 +/- 2.9 nM and 279 +/- 299 fmol/mg protein/h (mean +/- SD, n = 19) for HO, respectively. The aromatase activity was significantly increased by dexamethasone in a dose-dependent manner. Reverse transcription-polymerase chain reaction analysis revealed that dexamethasone increased the transcript of P450AROM gene. Osteoblast-specific promoters were also determined. Dexamethasone and 1 alpha,25-dihydroxyvitamin D3 synergistically enhanced aromatase activity and P450AROM mRNA expression. These results demonstrate that adrenal androgen, DHEA, is converted to E1 in osteoblast by P450AROM which is positively regulated by glucocorticoid and 1 alpha,25-dihydroxyvitamin D3 and important to maintain BMD in the 6 to 7th decade, after menopause.

Aged↗
PubMed1995

Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes.

Although evidence indicates that dehydroepiandrosterone (DHEA) exerts direct physiological effects, its mechanism of action remains unknown. DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line, PEER, revealing that a single class of high-affinity binding sites for DHEA (dissociation constant = 7.4 +/- 0.53 nmol/L, mean +/- SE, n = 4) was greatly increased when treated with DHEA, phorbol-12-myristate-13-acetate, and the Ca2+ ionophore A23187. Bound [3H]DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone, but not effectively by other steroids, including DHEA sulfate. These results not only indicate the existence of a DHEA receptor, but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation.

Binding Sites↗
PubMed1995

In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome.

To clarify whether adrenal gland secretes inhibin in vivo in physiological or pathological conditions, we measured the levels of inhibin-like immunoreactivity (inhibin-LI) in adrenal veins (A-vein) and compared them with those in inferior vena cava (IVC) using blood samples obtained at catheterization of adrenal vein in the patients with adrenal adenoma manifesting Cushing's syndrome (Cs), aldosterone-producing adenoma, clinically non-functioning adenoma and normal adrenal gland. The tumor sides of A-veins in the patients with adenomas and also both sides of A-veins in subjects with normal adrenal glands showed significantly higher contents of inhibin-LI than their IVC. When the inhibin-LI secretion rate from adrenal gland was estimated by the difference between the levels of A-vein (tumor side) and IVC, Cs adenomas showed the highest secretion rate. Similarly, the tissue inhibin-LI content and the basal secretion rate of inhibit-LI from primary cultured cells were the highest in Cs adenomas. These findings indicated that normal adrenal glands and adrenocortical adenomas produced and secreted inhibin-LI into the general circulation in vivo and Cs adenomas have relatively high capacity for secreting inhibin-LI, and the present study provided the first in vivo evidence for adrenal inhibin-LI production in pathological conditions.

Adrenal Cortex Neoplasms↗
PubMed1995

Cushing's disease preceding sarcoidosis.

We present a 32-year-old-woman with Cushing's disease and sarcoidosis. She had been diagnosed as having Cushing's disease in 1985. She had transsphenoidal surgery followed by pituitary radiation. Subsequently her plasma cortisol level gradually decreased to normal range. In 1991, she manifested bilateral hilar lymphadenopathy on chest X-ray, erythema nodosum, subcutaneous nodules and granulomatous uveitis. From the histological findings of the skin lesions, the patient was diagnosed as having sarcoidosis. Interestingly, an inverse relationship between the disease activity of sarcoidosis and the level of serum cortisol in Cushing's disease was observed in the clinical course of this patient. Co-existence of Cushing's disease and sarcoidosis is very rare. Since the therapeutic significance of steroids in sarcoidosis has been well established, this case provides insight to the relationship between sarcoidosis and steroids.

Adrenocorticotropic Hormone↗
PubMed1994

[A case of Rathke's cleft cyst with panhypopituitarism].

A 41-year-old man was admitted to our hospital because of general fatigue, sexual debility and finger stiffness. Endocrinological examinations revealed that he had panhypopituitarism, resulting in secondary adrenal insufficiency, hypothyroidism and gonadal failure. Computed tomography (CT) of the head demonstrated a low density intrasellar mass, while brain magnetic resonance imaging (MRI) showed a high intensity mass extending from the intrasellar to suprasellar region in both T1WI and T2WI. The mass was removed by transsphenoidal surgery and histologically diagnosed as Rathke's cleft cyst. Replacement with hydrocortisone and levothyroxine sodium greatly improved the clinical symptoms. Rathke's cleft cyst causing panhypopituitarism is relatively rare. The clinical and endocrinological characteristics of Rathke's cleft cyst were discussed based on the findings in 49 Japanese cases including this case and two other cases we have experienced.

Adult↗
PubMed1994

Pancreastatin-like immunoreactivity of cerebrospinal fluid in patients with Alzheimer type dementia: evidence of aberrant processing of pancreastatin in Alzheimer type dementia.

The concentrations of pancreastatin-like immunoreactivity (PST-LI) of the cerebrospinal fluid (CSF) were measured in the patients with Alzheimer type dementia (ATD) and in age-matched normal subjects. The mean PST-LI concentration in the CSF of ATD patients was significantly lower than that of normal subjects. Gel chromatographic analysis revealed that the main PST-LI peak of ATD's CSF eluted at molecular weight (MW) 13.5 kDa. However, the age-related change of the molecular forms of PST-LI in CSF was observed in normal subjects as following; PST-LI in neonatal CSF showed one peak at MW 13.5 kDa, that of 16-64-year-old showed two peaks at MW 13.5 and 5.4 kDa, however, only one main peak was shown at MW 5.4 kDa in the CSFs of 72-85-year-old. These findings suggest that the production of PST-LI was decreased and the proteolytic cleavage, which should process big PST to PST (1-52) in normal subjects, was altered to that of neonatal type in the CNS of the patients with ATD.

Aged↗
PubMed1994

[Isolated gonadotropin deficiency and secretory discrepancy of cortisol and adrenal androgen by hemochromatosis secondary to congenital dyserythropoietic anemia].

A 37-yr-old woman was admitted to our hospital for evaluation of diabetes mellitus, liver cirrhosis and primary amenorrhea. Serological and hematological examinations revealed that she suffered from hemochromatosis secondary to congenital dyserythropoietic anemia (CDA), characterized by ineffective hematopoiesis and erythropoietic dysplasia. Iron deposition was suggested by MRI on the pancreas, liver and pituitary gland. Endocrinological examinations demonstrated that she had isolated gonadotropin deficiency and ovarian failure, resulting in hypogonadotropic hypogonadism. In addition, despite normal responses of serum cortisol and plasma aldosterone to ACTH and furosemide-standing tests, respectively, serum dehydroepiandrosterone (DHEA) responded poorly to ACTH test, suggesting selective damage of zona reticularis in adrenocortical steroidogenesis in association with hemochromatosis.

Adrenal Cortex↗
PubMed1994

No mutation in cytochrome P450 side chain cleavage in a patient with congenital lipoid adrenal hyperplasia.

Molecular basis of lipoid adrenal hyperplasia (lipoid CAH) in a Japanese patient was investigated. A 46XY Japanese female patient was clinically diagnosed as having lipoid CAH based on her clinical history of adrenal crisis at birth and the low basal concentrations of cortisol, aldosterone, adrenal androgens and testosterone in serum. In vitro studies of testicular mitochondrial enzymes confirmed a specific impairment of cholesterol side chain cleavage (SCC) activity. However, in spite of the virtual reduction of SCC activity, the amounts of immunodetectable P450scc, adrenodoxin reductase, and adrenodoxin in testicular mitochondria were almost same as those of normal testis. Furthermore, the size of each protein was similar to that of normal testis. Enzymatic amplification of the complementary DNA encoding P450scc from the patient's testis RNA and its nucleotide analysis by direct sequencing revealed no mutation. These results indicate that defective P450scc is not the lesion in this patient, confirming a previous report showing no P450scc mutations in patients with lipoid CAH. The exact lesion causing lipoid CAH in this patient is currently unknown.

Adolescent↗
PubMed1994

Catechol estrogens are more potent antioxidants than estrogens for the Cu(2+)-catalyzed oxidation of low or high density lipoprotein: antioxidative effects of steroids on lipoproteins.

In order to clarify the mechanism of antiatherogenic action of several steroids such as estrogens, dehydroepiandrosterone (DHEA) and dexamethasone, we investigated the effects of various steroids on the copper (Cu2+)-catalyzed oxidation of low density lipoprotein (LDL) or high density lipoprotein (HDL) in 0.15 M NaCl by measuring thiobarbituric acid-reactive substances (TBARS). At a concentration of 10(-5) M, estrogens strongly protected against LDL oxidation by 0.5 microM Cu2+ in the following order of inhibition: estradiol (E2) (75%), estrone (E1) (35%) and estriol (E3) (30%). However, the corresponding metabolites of these estrogens, the catechol estrogens, had an even more protective effect on LDL oxidation by 0.5 microM Cu2+ in the following order of inhibition: 2-hydroxyestradiol (2-OHE2) (98%), 2-OHE1 (97%) and 2-OHE3 (96%). E2 and 2-OHE2 from 10(-7) M to 10(-5) M inhibited LDL oxidation in a dose-dependent manner, with a more marked effect for oxidation by 0.1 microM Cu2+ than by 0.5 microM Cu2+. 10(-5) M dexamethasone produced a slight (10%) but significant inhibition of LDL oxidation by 0.5 microM Cu2+. In addition, the estrogens and catechol estrogens were also effective in protecting against HDL oxidation by 0.5 microM Cu2+. Other steroids including DHEA and DHEA-sulfate had no antioxidative effects on either LDL or HDL in this system. These results indicate that estrogens and their metabolites, the catechol estrogens, exert antioxidative effects on both LDL and HDL. The catechol estrogens may be more important antioxidants than estrogens for both LDL and HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidants↗
PubMed1994

Age-related increase in neuropeptide Y-like immunoreactivity in cerebrospinal fluid in women.

In order to investigate the age-related changes in neuropeptide Y (NPY) in cerebrospinal fluid (CSF) of men and women, we examined the concentration of NPY-like immunoreactivity (NPY-LI) in CSF of a large population of Japanese men and women by specific radioimmunoassay (RIA). The dilution curve of CSF extract paralleled the standard curve of RIA for human NPY. Gel chromatographic studies revealed the presence of two peaks of NPY-LI, one emerging at the elution position of synthetic NPY and another emerging at a higher-molecular-weight position. NPY-LI in the CSF in 201 men (aged 17 to 69y) and 118 women (aged 17 to 69y) was 124 +/- 4 and 136 +/- 6 pg/ml (mean +/- SE), respectively. NPY-LI in the CSF of women, but not of men, increased significantly with aging. This finding suggests that the level of NPY with aging in the central nervous system (CNS) may be regulated somewhat differently in men and women.

Adolescent↗
PubMed1992

Partial purification of phosphoramidon-sensitive endothelin converting enzyme in porcine aortic endothelial cells: high affinity for Ricinus communis agglutinin.

A membrane-bound endothelin converting enzyme (ECE) of porcine aortic endothelial cells (ECs) was solubilized with Lubrol PX with high efficiency and stability. The solubilized ECE was bound to Ricinus communis agglutinin (RCA) but not to peanut agglutinin (PNA) or wheat germ agglutinin (WGA), suggesting that the ECE has a galactosylated structure possessing a high affinity for RCA. The sequential chromatography on RCA-agarose, PNA-agarose and a TSKgel DEAE-5PW column attained 2,100-fold purification for the ECE over the membrane fractions. The purified ECE was sensitively inhibited by phosphoramidon but not by thiorphan. The present RCA and PNA affinity column procedures may be a powerful approach to isolation of ECE of EC origin.

Animals↗
PubMed1992

Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor.

We isolated a cDNA encoding type-1 angiotensin II receptor from a human liver cDNA library. The cDNA had an open reading frame encoding a protein of 359 amino acid residues with a relative Mr of 41,060. The deduced amino acid sequence of the human angiotensin II (Ang II) receptor was 95.3% and 94.2% identical to those of bovine and rat type-1 Ang II receptors, respectively, and had a significant similarity with the G protein-coupled receptor. The rank order of the binding to the receptor expressed in COS-7 cells was Ang II greater than Ang III greater than Ang I. The expression of the Ang II receptor mRNA was detected in human liver, lung, adrenal and adrenocortical adenomas but not in adrenomedullary tumor, pheochromocytoma, by Northern blot analysis.

Amino Acid Sequence↗
PubMed1992

A single amino acid substitution (Met786----Val) in the steroid-binding domain of human androgen receptor leads to complete androgen insensitivity syndrome.

Androgen receptors (ARs) in two Japanese siblings with complete androgen insensitivity syndrome were characterized, and their molecular bases were investigated. Androgen binding was undetectable in cultured pubic skin fibroblasts from the patients by whole cell assay. Sequence analysis of exons B-H, which encode the DNA- and steroid-binding domains, of the AR gene from these patients using polymerase chain reaction revealed a single nucleotide substitution in exon F, resulting in an amino acid change at 786 from methionine (ATG) to valine (GTG) within the steroid-binding domain of AR. Reconstruction of this mutation by site-directed mutagenesis into human AR cDNA followed by expression in COS-1 cells led to production of the same amount and the same molecular mass of immunodetectable AR protein as those found with expression of the normal human AR cDNA. However, in contrast to wild-type AR expressed in COS-1 cells, the mutant AR showed markedly low affinity of androgen binding by whole cell assay. These results suggest that androgen resistance in these patients is due to the point mutation in the steroid-binding domain of the AR.

Adult↗
PubMed1992

Disordered expression of adrenal steroidogenic P450 mRNAs in incidentally discovered nonfunctioning adrenal adenoma.

In order to elucidate the steroidogenesis of clinically nonfunctioning adrenocortical adenoma, we studied the aldosterone, cortisol (F) and dehydroepiandrosterone (DHEA) content and the expression of mRNA of cytochrome P450 for side chain cleavage (P450scc), 17 alpha-hydroxylase (P450c17). 21-hydroxylase (P450c21) and 11 beta-hydroxylase (P450c11) in four clinically nonfunctioning adrenocortical adenomas discovered incidentally in asymptomatic patients (Cases 1, 2, 3 and 4). The results were compared with those in normal adrenal glands. In the adenomas from cases 1 and 2, the abundance of steroidogenic P450s mRNA were similar to those in normal adrenal glands, except P450c11 mRNA expression in the adenoma from case 1 which was slightly higher than normal. The steroid content was normal level, except for higher F in the adenoma from case 1 and lower aldosterone in case 2 adenoma than normal. The adenoma from case 3 contained much less P450scc, P450c17 and P450c21 mRNA, while the amount of P450c11 mRNA was slightly greater than in normal adrenals. The adenoma showed normal aldosterone, high F and low DHEA content compared with normal adrenal glands. In the adenoma from case 4, the accumulation of all four P450 mRNAs decreased, whereas aldosterone, F and DHEA content in the adenoma was similar to that of normal adrenal glands. These data indicated that nonfunctioning adrenocortical adenoma showed similar or decreased expression of steroidogenic P450 mRNAs that the normal adrenal gland. This decreased expression of steroidogenic P450 mRNAs may be at least partly concerned with the absence of clinical symptoms in patients with nonfunctioning adenoma.

Adenoma↗