Motomura, Naoki Yamazaki, Yuto Koga, Daiki Harashima, Shogo Gao, Xin Tezuka, Yuta Omata, Kei Ono, Yoshikiyo Morimoto, Ryo Satoh, Fumitoshi Nakamura, Yasuhiro Kwon, Go Eun Choi, Man Ho Ito, Akihiro Sasano, Hironobu 2024-01-19T12:33:37Z 2024-01-19T12:33:37Z 2022-04-05 2022-02 1661-6596 https://pubs.kist.re.kr/handle/201004/115652 Cortisol-producing adenoma (CPA) is composed of clear and compact cells. Clear cells are lipid abundant, and compact ones lipid poor but associated with higher production of steroid hormones. PRKACA mutation (PRKACA mt) in CPA patients was reported to be associated with more pronounced clinical manifestation of Cushing's syndrome. In this study, we examined the association of histological features and genotypes with cholesterol uptake receptors and synthetic enzymes in 40 CPA cases, and with the quantitative results obtained by gas chromatography-mass spectrometry (GC-MS) analysis in 33 cases to explore their biological and clinical significance. Both cholesterol uptake receptors and synthetic enzymes were more abundant in compact cells. GC-MS analysis demonstrated that the percentage of compact cells was inversely correlated with the concentrations of cholesterol and cholesterol esters, and positively with the activity of cholesterol biosynthesis from cholesterol esters. In addition, hormone-sensitive lipase (HSL), which catalyzes cholesterol biosynthesis from cholesterol esters, tended to be more abundant in compact cells of PRKACA mt CPAs. These results demonstrated that both cholesterol uptake and biosynthesis were more pronounced in compact cells in CPA. In addition, more pronounced HSL expression in compact cells of PRKACA mt CPA could contribute to their more pronounced clinical manifestation. English Multidisciplinary Digital Publishing Institute (MDPI) The Association of Cholesterol Uptake and Synthesis with Histology and Genotype in Cortisol-Producing Adenoma (CPA) Article 10.3390/ijms23042174 1 International Journal of Molecular Sciences, v.23, no.4 International Journal of Molecular Sciences 23 4 Y scie scopus 000765973700001 2-s2.0-85124613814 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article HORMONE-SENSITIVE LIPASE CATALYTIC SUBUNIT CUSHINGS-SYNDROME SOMATIC MUTATIONS PRKACA MUTATIONS RECEPTOR LESIONS BI Cushing&apos s syndrome cortisol producing adenoma cholesterol uptake de novo synthesis HSL PRKACA immunohistochemistry mass spectrometry