Bose Himangshu S, Rice Alan M, Marshall Brendan, Gebrail Fadi, Kupshik David, Perry Elizabeth W
Laboratory of Biochemistry, Biomedical Sciences, Mercer University School of Medicine, Savannah, Georgia, USA.
Memorial University Medical Center, Savannah, Georgia, USA.
Endocrinol Diabetes Metab Case Rep. 2019 May 3;2019. doi: 10.1530/EDM-19-0009.
Steroid hormones are essential for the survival of all mammals. In adrenal glands and gonads, cytochrome P450 side chain cleavage enzyme (SCC or CYP11A1), catalyzes conversion of cholesterol to pregnenolone. We studied a patient with ambiguous genitalia by the absence of Müllerian ducts and the presence of an incompletely formed vagina, who had extremely high adrenocorticotropic hormone (ACTH) and reduced pregnenolone levels with enlarged adrenal glands. The testes revealed seminiferous tubules, stroma, rete testis with interstitial fibrosis and reduced number of germ cells. Electron microscopy showed that the patient's testicular mitochondrial size was small with little SCC expression within the mitochondria. The mitochondria were not close to the mitochondria-associated ER membrane (MAM), and cells were filled with the microfilaments. Our result revealed that absence of pregnenolone is associated with organelle stress, leading to altered protein organization that likely created steric hindrance in testicular cells. Learning points: Testes revealed seminiferous tubules, stroma, rete testis with interstitial fibrosis and reduced number of germ cells; Testicular mitochondrial size was small with little SCC expression within the mitochondria; Absence of pregnenolone is associated with organelle stress.
类固醇激素对所有哺乳动物的生存至关重要。在肾上腺和性腺中，细胞色素P450侧链裂解酶（SCC或CYP11A1）催化胆固醇转化为孕烯醇酮。我们研究了一名生殖器模糊的患者，其苗勒管缺如且阴道发育不完全，促肾上腺皮质激素（ACTH）水平极高，孕烯醇酮水平降低，肾上腺增大。睾丸可见生精小管、间质、睾丸网伴间质纤维化，生殖细胞数量减少。电子显微镜显示，患者睾丸线粒体体积小，线粒体内SCC表达极少。线粒体未靠近线粒体相关内质网膜（MAM），细胞内充满微丝。我们的结果表明，孕烯醇酮缺乏与细胞器应激有关，导致蛋白质组织改变，可能在睾丸细胞中造成空间位阻。学习要点：睾丸可见生精小管、间质、睾丸网伴间质纤维化，生殖细胞数量减少；睾丸线粒体体积小，线粒体内SCC表达极少；孕烯醇酮缺乏与细胞器应激有关。
