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Kawasaki, Japan

Takizawa I.,Niigata University | Nishiyama T.,Niigata University | Hara N.,Niigata University | Hoshii T.,Niigata University | And 3 more authors.
Cancer Letters | Year: 2010

The intracellular androgen metabolism and cell activity in prostate cancer cells with mutated (LNCaP-FGC) or wild-type (VCaP) androgen receptors in the presence of trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, were examined. Trilostane suppressed the intracellular production of androstenedione, testosterone, and dihydrotestosterone from dehydroepiandrosterone in LNCaP-FGC cells. In both LNCaP-FGC and VCaP cell types, the prostate-specific antigen (PSA) levels in media were increased by trilostane alone in a concentration-dependent manner. Both cells pretreated with trilostane showed a dose-dependent decrease in PSA production with bicalutamide (P< 0.001). Trilostane should be used with particular concern when treating prostate cancer. © 2010 Elsevier Ireland Ltd. Source

Inoue T.,Tohoku University | Inoue T.,Kao Corporation | Miki Y.,Tohoku University | Abe K.,Tohoku University | And 9 more authors.
Molecular and Cellular Endocrinology | Year: 2012

Sex steroids have been known to play important roles in the homeostasis of human skin, but little is known about their biosyntheses in that tissue. In this study, we characterized the correlation between the concentrations of sex steroids and the expression levels of the factors involved in their synthesis or metabolism in human skin. The expression levels of aromatase (ARO) and steroidogenic acute regulatory protein (StAR) were positively correlated with estrogens and testosterone concentrations, respectively. We demonstrated that estrogen synthesis was markedly decreased by ARO inhibitor and that skins with higher ARO expression had thicker elastic fibers than those with lower ARO expression. While pregnenolone and testosterone concentrations were increased by cholesterol administration to epidermal keratinocytes. Scalp skin with higher StAR expression was cleared to have significantly fewer hair follicles than that with lower expression. Our results suggest that the status of ARO and StAR contribute to estrogen synthesis in situ, especially for the regulation of elastic fiber formation, and to testosterone synthesis, which may be associated with hair growth, respectively. © 2012 Elsevier Ireland Ltd. Source

Rege J.,University of Georgia | Nakamura Y.,Tohoku University | Satoh F.,Tohoku University | Morimoto R.,Tohoku University | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Abroad analysis of adrenal gland-derived 19-carbon (C 19) steroids has not been reported. This is the first study that uses liquid chromatography-tandem mass spectrometry to quantify 9 C19 steroids (androgens and their precursors), estrone, and estradiol in the adrenal vein (AV) of women, before and after ACTH stimulation. Objective: The objective of this study was to define the adrenal androgen metabolome in women before and after ACTH infusion. Design: This was a retrospective study. Patients: Seven women, aged 50.4±5.4 years, with suspected diagnosis of an adrenal aldosterone-producing adenoma were included in the study. Methods: AV and iliac serum samples were collected before and after administration of ACTH (15 minutes). AV samples were analyzed using for concentrations of 9 unconjugated C19 steroids, estrone, and estradiol. Dehydroepiandrosterone sulfate (DHEA-S) was quantified by radioimmunoassay. Results: AV levels of DHEA-S were the highest among the steroids measured. The most abundant unconjugated C 19 steroids in AV were 11β-hydroxyandrostenedione (11OHA), dehydroepiandrosterone (DHEA), and androstenedione (A4). ACTH significantly increased the adrenal output of 9 of the 12 steroids that were measured. ACTH increased the mean AV concentration of DHEA-S by 5-fold, DHEA by 21-fold, A4 by 7-fold, and 11OHA by 5-fold. 11β-Hydroxytestosterone and testosterone were found to be potent androgen receptor agonists when tested with an androgen-responsive cell reporter model. Conclusion: The current study indicates that the adrenal gland secretes primarily 3 weak androgens, namely DHEA, 11OHA, and A4. Active androgens, including testosterone and 11β- hydroxytestosterone, are also produced but to a lesser degree. Copyright © 2013 by The Endocrine Society. Source

Morizane S.,Keio University | Mitani F.,Keio University | Mitani F.,Waseda University | Ozawa K.,Keio University | And 13 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

Objective-: The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt. Methods And Results-: Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT1 receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy. Conclusion-: Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone. © 2012 American Heart Association, Inc. Source

Nakamura Y.,University of Georgia | Nakamura Y.,Tohoku University | Rege J.,University of Georgia | Satoh F.,Tohoku University | And 6 more authors.
Clinical Endocrinology | Year: 2012

Context Although steroid hormones produced by the adrenal gland play critical roles in human physiology, a detailed quantitative analysis of the steroid products has not been reported. The current study uses a single methodology (liquid chromatography-tandem mass spectrometry, LC-MS/MS) to quantify ten corticosteroids in adrenal vein (AV) samples pre- and post-adrenocorticotropic hormone (ACTH) stimulation. Design/methods Three men and six women with a diagnosis of an adrenal aldosterone-producing adenoma (APA) were included in the study. Serum was collected from the iliac vein (IV) and the AV contralateral to the diseased adrenal. Samples were collected, before and after administration of ACTH. LC-MS/MS was then used to quantify serum concentrations of unconjugated corticosteroids and their precursors. Results Prior to ACTH stimulation, the four most abundant steroids in AV were cortisol (90%), cortisone (4%), corticosterone (3%) and 11-deoxycortisol (0·8%). Post-ACTH administration, cortisol remained the major adrenal product (79%); however, corticosterone became the second most abundantly produced adrenal steroid (11%) followed by pregnenolone (2·5%) and 17α- hydroxypregnenolone (2%). ACTH significantly increased the absolute adrenal output of all ten corticosteroids measured (P < 0·05). The four largest post-ACTH increases were pregnenolone (300-fold), progesterone (199-fold), 17α-hydroxypregnenolone (187-fold) and deoxycorticosterone (82-fold). Conclusion Using LC-MS/MS, we successfully measured 10 corticosteroids in peripheral and AV serum samples under pre- and post-ACTH stimulation. This study demonstrates the primary adrenal steroid products and their response to ACTH. © 2012 Blackwell Publishing Ltd. Source

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