Expression of Salt-Inducible Kinase (SIK) Isoforms in Human Adrenal Glands with Hyperaldosteronism

Presentation Number: MON 388
Date of Presentation: April 3rd, 2017

Yuto Yamazaki*1, Yasuhiro Nakamura2, Miyuki Mukai3, Kazue Ise1, Kei Omata4, Yoshikiyo Ono1, Yuta Tezuka1, Ryo Morimoto1, Fumitoshi Satoh1 and Hironobu Sasano5
1Tohoku University Graduate School of Medicine, Sendai, Japan, 2Tohoku Medical and Pharmaceutical University, Sendai, Japan, 3Depatment of Pathology, Tohoku Graduate Schol of Medicine, 4Tohoku University, Sendai, Japan, 5Tohoku University School of Medicine, Sendai, Japan

Abstract

Introduction: SIK (Salt-inducible kinase) is a member of sodium-induced serine threonine protein kinase family composed of several isoforms. Among these isoforms, SIK1 was reported to be involved in the regulation of steroid biosynthesis in mouse Y-1 cell line through inhibiting cAMP induced pathway. Three isoforms, SIK1, SIK2 and SIK3, were subsequently identified in human and SIK2 and SIK3 also reported to regulate cell proliferation. However, their distribution and biological functions in human adrenals have remained unknown. Therefore, we examined the expression profiles of SIK isoforms in human normal and pathological adrenals and also explored the regulation of their mRNA expression in vitro.

Materials and Methods: We assessed mRNA expression levels of SIK isoforms in APA (Aldosterone-producing adenoma) and CPA (Cortisol-producing adenoma) tissues using q-PCR, and correlated the results with steroidogenic enzymes. We then assessed mRNA levels of individual SIK isoforms using human adrenocortical carcinoma cell lines treated by Angiotensin and Forskolin. We also immunolocalized SIK3 in APA and CPA cases.

Results: Both SIK2 and SIK3 mRNAs were significantly positively correlated with HSD3B2 and SIK3 was also significantly inversely correlated with CYP17. SIK isoforms expression was induced by both Angiotensin and Forskolin treatment. SIK3 was immunolocalized in the tumor cells of both APA and CPA but mainly in zona glomerulosa cells in normal adrenocortex.

Discussion: SIKs could be possibly involved in the regulation of aldosterone biosynthesis in human adrenal glands via cAMP pathway. In addition, SIK2 and SIK3 could also regulate adrenocortical tumor cell proliferation.

 

Nothing to Disclose: YY, YN, MM, KI, KO, YO, YT, RM, FS, HS