Keio University

New Molecular Imaging Method Identifies Steroid Hormone-Producing Cells Causing Hypertension in Patient-Derived Tissues—Hopes for Biomarker Discovery in Patients with Primary Aldosteronism—

Publish: October 23, 2018
Public Relations Office

October 23, 2018

Keio University School of Medicine

A research group from the Department of Biochemistry, Keio University School of Medicine, led by Senior Lecturer Yuki Sugiura and Part-time Lecturer Koushiro Nishimoto (who also serves at the Department of Urologic Oncology, Saitama Medical University International Medical Center), in collaboration with Associate Professor Shuichi Shimma of Osaka University and Honorary Director Tetsuo Nishikawa of Yokohama Rosai Hospital, has successfully visualized the localization of aldosterone—a steroid hormone that causes hypertension—in rat and human adrenal tissues using a "new high-sensitivity imaging mass spectrometry method." This novel technique acquires images with far greater sensitivity than conventional imaging mass spectrometry by derivatizing steroid hormones on tissue sections.

The adrenal cortex in mice and rats was known to have a layered structure, with each layer producing substances such as aldosterone, cortisol, and sex hormones. The research group had previously suggested that the adult human adrenal cortex is more mottled than layered and that granular aldosterone-producing cell clusters (named APCCs) are the primary sites of aldosterone production, but actual visualization had not yet been achieved.

Now, using the new high-sensitivity imaging mass spectrometry method, the team has successfully captured images showing that cell groups called APCCs in hypertensive patients produce aldosterone in the adrenal gland. They have also reported images showing that granular APCC cell groups can enlarge into giant aldosterone-producing adenomas (APAs), which produce even more aldosterone. Furthermore, through image analysis, they were able to identify abnormal molecular species of steroid hormones that are produced only by abnormal APCCs and APAs and are not found in normal adrenal cortical cells.

These research findings clarify that APCCs, present in patients with mild hypertension, are the origin of APAs, the lesions responsible for severe primary aldosteronism. This is also expected to advance the development of biomarkers for identifying patients who have developed APCCs or APAs.

The results of this research were published in *Hypertension* on October 22, 2018 (US Eastern Time). The content is also the subject of an Editorial Commentary in the same journal.

Please see below for the full press release.

Press Release (PDF)