Sex-specific differences in the incidence of urinary bladder carcinomas are well known, and the possible involvement of sex steroids has been proposed. We previously reported the association of the loss of androgen receptors and androgen-producing enzymes with tumor progression of urinary bladder cancer patients. Clinically, the selective estrogen receptor modulators (SERMs) were reported to suppress the progression of these tumors but the status of estrogen receptors (ERs) has not been well studied in patients with bladder urinary cancer. Moreover, not only ERs but also estrogen-related enzymes, such as aromatase, steroid sulfatase (STS), and estrogen sulfotransferase (EST), have been reported in the biological/clinical behavior of various hormone-dependent carcinomas but not studied in urinary bladder carcinoma. Therefore, in this study, we immunolocalized ERs as well as estrogen metabolizing enzymes in urinary bladder carcinoma and performed immunoblotting and cell proliferation assays using the bladder urothelial carcinoma cell line, T24. The results revealed that the loss of STS and aromatase was significantly correlated with advanced stages of the carcinoma. In vitro studies also revealed that T24 cell proliferation rates were significantly ameliorated after treatment with estradiol or diarylpropionitrile (DPN). EST and aromatase were also significantly correlated with the nuclear grade of the carcinoma. The results of our present study, for the first time, demonstrated that biologically active estrogens that bind to ERs could suppress tumor progression and the inactive ones could promote its progression and the potential clinical utility of SERM treatment in selective patients with urinary bladder carcinoma.

Primary aldosteronism (PA) is considered the most common form of secondary hypertension, which is associated with excessive aldosterone secretion in the adrenal cortex. The cause of excessive aldosterone secretion is the induction of aldosterone synthase gene (CYP11B2) expression by depolarization of adrenocortical cells. In this study, we found that YM750, an Acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, acts on adrenocortical cells to suppress CYP11B2 gene expression and aldosterone secretion. YM750 inhibited the induction of CYP11B2 gene expression by KCl stimulation, but not by angiotensin II and forskolin stimulation. Interestingly, YM750 did not inhibit KCl-stimulated depolarization via an increase in intracellular calcium ion concentration. Moreover, ACAT1 expression was relatively abundant in the zona glomerulosa (ZG) including these CYP11B2-positive cells. Thus, YM750 suppresses CYP11B2 gene expression by suppressing intracellular signaling activated by depolarization. In addition, ACAT1 was suggested to play an important role in steroidogenesis in the ZG. YM750 suppresses CYP11B2 gene expression and aldosterone secretion in the adrenal cortex, suggesting that it may be a potential therapeutic agent for PA.

Background: In the present study, we focused on the periostin expression in Warthin’s tumor and malignant lymphomas, which require differentiation from these tumors. Objectives: we investigated the expression and the roles of periostin in the formation of parotid gland mass. Methods: Twenty-eight samples of parotid gland mass were investigate histopathologically and immunohistochemically. Result: Pathologically, tumors were diagnosed as Warthin’s tumors in 15 specimens and malignant lymphomas in 13 specimens. Increased periostin expression was observed in the stroma of Warthin's tumor and malignant lymphoma in 24 of 28 samples (12 Warthin's tumor, 12 malignant lymphoma) (85.7%). Periostin expression was observed in three different patterns: negative, superficial, and infiltrative. Statistically significant differences were found between the histological classification of the tumors and periostin expression patterns. When periostin expression was examined in the same 28 specimens, increased periostin expression was observed in the tumor capsule in 13 specimens (46.4%). A statistically significant association was found between the presence or absence of periostin expression within the tumor capsule and the histology of parotid tumors. Conclusion and significance: Periostin may be involved in the development of Warthin's tumor and malignant lymphoma. Periostin may serve as a new biomarker for these diseases.