Biomedical subjects

Tomoatsu Mune

Publications and source records attributed to Tomoatsu Mune.

22 records · Page 2Linked to original sources

PubMed2002

Altered corticosteroid metabolism differentially affects pituitary corticotropin response.

To evaluate the effects of altered corticosteroid metabolism on the hypothalamic-pituitary-adrenal axis, we examined rats treated with glycyrrhizic acid (G rats) or rifampicin (R rats) for 7 days. The half-life of exogenously administered hydrocortisone as a substitute for corticosterone was longer in G rats and shorter in R rats, with no differences in basal plasma levels of ACTH or corticosterone. The ACTH responses to human corticotropin-releasing factor (CRF) or insulin-induced hypoglycemia were greater in G rats and tended to be smaller in R rats compared with those in the control rats, whereas the corticosterone response was similar. No difference was observed in the content and mRNA level of hypothalamic CRF among the groups. The number and mRNA level of CRF receptor and type 1 11 beta-hydroxysteroid dehydrogenase (11-HSD1) mRNA level in the pituitary were increased in G rats but not changed in R rats, suggesting that chronically increased intrapituitary corticosterone upregulates pituitary CRF receptor expression. In contrast, CRF mRNA levels in the pituitary were increased in R rats. Our data indicate novel mechanisms of corticosteroid metabolic modulation and the involvement of pituitary 11-HSD1 and CRF in glucocorticoid feedback physiology.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2002

Eutopic overexpression of vasopressin v1a receptor in adrenocorticotropin-independent macronodular adrenal hyperplasia.

Arginine vasopressin (AVP) stimulates cortisol secretion through its vascular type V(1a) receptor in the adrenal glands, in addition to stimulating ACTH secretion through pituitary V(3) receptor. Because hyper-response of plasma cortisol to vasopressin is documented in some patients with Cushing's syndrome due to adrenal adenoma (CS) or ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), we analyzed the expression of V(1a), V(2), V(3) receptor and AVP mRNA in human adrenal tissues by quantitative competitive RT-PCR or real-time PCRs. V(1a) receptor mRNA levels (ratio against glyceraldehyde 3-phosphate dehydrogenase) were 0.378 +/- 0.143 (mean +/- SE) in preclinical CS (n = 5) and 0.630 +/- 0.072 in AIMAH (n = 4), which were significantly higher than those (0.046 +/- 0.012; n = 9) in control adrenals, whereas those in overt CS (0.143 +/- 0.048; n = 10) or aldosterone-producing adenomas (0.069 +/- 0.018; n = 12) were similar to control adrenals. Although ectopic expression of V(2) or V(3) receptor was detected in half of AIMAH cases, the absolute levels were low. Furthermore, V(1a) receptor mRNA levels in the adjacent adrenal glands (0.190 +/- 0.039, n = 9) of aldosterone-producing adenomas were higher than those in control adrenals and in the corresponding tumor portions (0.079 +/- 0.024). In contrast, there were no significant differences in AVP mRNA levels among these groups. These results suggest that eutopic V(1a) receptor overexpression is involved in the etiology of AIMAH and a subset of adrenal adenomas causing overt or preclinical Cushing's syndrome. Our results imply a possible association of V(1a) receptor expression with adrenal hyperplasia.

Adrenal Gland Diseases↗

PubMed2002

11beta-hydroxysteroid dehydrogenase type 2 is expressed in the human kidney glomerulus.

Our previous study demonstrated that the GR is expressed in the human kidney glomerulus. The function of the GR of glomerular cells might be affected by the concentration of intracellular glucocorticoids, which is modulated by 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). Because the expression of 11betaHSD2 in the glomerular cells remains unclear, we used competitive RT-PCR and immunoblotting to detect the expression of 11betaHSD2 mRNA and protein in isolated human glomeruli, in whole kidney cortex as a positive control, and in a human glomerular visceral epithelial cell line. 11betaHSD2 mRNA was detected in all samples. Specific antihuman 11betaHSD2 antibody recognized a single band at 41 kDa, consistent with the molecular mass of human 11betaHSD2, in the samples of the isolated glomeruli and whole kidney cortex. Furthermore, definite 11betaHSD2 enzymatic activity was also determined with the sample of isolated glomeruli. We also performed immunohistochemistry by light and electron microscopy to determine the cellular and subcellular localization of 11betaHSD2 in the human glomeruli. Immunoreactivity of the enzyme was clearly observed in the glomerular visceral epithelial cells and endothelial cells as well as in the distal convoluted tubules and collecting ducts. The subcellular localization of 11betaHSD2 was shown to be endoplasmic reticulum. These results suggest that 11betaHSD2 might play a crucial role in modulating the intracellular concentration of glucocorticoids in human glomerular cells.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2002

Variant of pre-clinical Cushing's syndrome: hypertension and hypokalemia associated with normoreninemic normoaldosteronism.

The case of a 48-year-old woman with a left adrenocortical adenoma and showing hypokalemia, hypertension and normoreninemic normoaldosteronism is reported. Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol levels were within the reference ranges. The patient's plasma cortisol level decreased insufficiently at night, and was insufficiently decreased by nighttime administration of dexamethasone. She showed no Cushingnoid stigmata. Iodocholesterol scintigraphy revealed tumor-sided uptake alone. The plasma dehydroepiandrosterone-sulfate level was low-to-normal for her age. Metabolic alkalosis and increased potassium clearance after sodium thiosulfate loading were revealed. The plasma aldosterone level was within the normal range, but it was statistically higher than the range for patients with pre-clinical Cushing's syndrome. However, peripheral plasma renin activity (PRA) increased normally after the patient resumed an upright posture following furosemide administration. After adenomectomy the hypokalemia and hypertension were resolved, and the plasma ACTH, cortisol, and PRA remained within the reference ranges. The plasma aldosterone level decreased slightly, but also remained within the reference range after adenomectomy. Paradoxical hyperplasia in the non-neoplastic adrenal glomerulosa zone, which indicates primary aldosteronism, and slight atrophy of the non-neoplastic adrenal cortex, which indicates pre-clinical Cushing's syndrome, were demonstrated. These findings satisfied the criteria of pre-clinical Cushing's syndrome, but did not completely satisfy those of primary aldosteronism. However, the level of CYP11 B2 mRNA in the tumor was in the lower-limit of the range for adenomas associated with primary aldosteronism and was higher than the ranges for adenomas associated with pre-clinical Cushing's syndrome and overt Cushing's syndrome. Based on these results, this case was suspected to constitute a variant of pre-clinical Cushing's syndrome with slight hypersecretion of aldosterone.

Adenoma↗