Sawetawan C, Rainey W E, Word R A, Carr B R
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
J Soc Gynecol Investig. 1995 Jan-Feb;2(1):30-7.
To ascertain the steroidogenic profile and location of steroidogenic enzymes in a steroid-secreting Sertoli-Leydig cell tumor of the ovary.
Steroid levels from peripheral, left ovarian (tumor), and right ovarian venous blood were measured. Tumor tissue was examined for the steroidogenic enzymes 17 alpha-hydroxylase (P450c17) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) by immunohistochemistry. Tumor cells were isolated and incubated in serum-free media. Thereafter, media were analyzed for steroid production, steroidogenic response to effectors, and metabolism of radiolabeled pregnenolone and androstenedione.
Levels of C19 steroids and 17-hydroxyprogesterone (17OHP) were elevated in peripheral blood. The majority (80%) of steroids in serum from the left ovarian vein (tumor) were C19 steroids (dehydroepiandrosterone [DHEA], 45%; androstenedione, 27%, testosterone, 7%, with 13% 17OHP, 7% progesterone, and less than 1% estradiol (E2). Immunoreactivity for both P450c17 and 3 beta HSD was identified in clusters of large cells surrounded by nonimmunoreactive cells composing cord-like structures. Of the steroids that accumulated in the incubation medium of unstimulated, freshly isolated tumor cells, 84% were C19 steroids (DHEA, 44%; androstenedione, 36%; testosterone 2%, with 16% 17OHP and less than 1% progesterone and E2. Basal steroid production was not stimulated by LH or FSH. However, treatment with forskolin (10 mumol/L), dibutyryl cAMP (1 mmol/L), or steroid precursors (22-hydroxycholesterol, 1 mumol/L; pregnenolone, 1 mumol/L) increased the production of all steroids measured. Forskolin treatment increased androstenedione (fivefold), DHEA (tenfold), and 17OHP (40-fold) compared with basal levels. Incubation of freshly isolated cells with [3H]pregnenolone demonstrated the ability of these cells to metabolize this C21 steroid precursor to androstenedione, DHEA, and 17OHP. However, [3H]androstenedione was not readily metabolized by these cells to either estrone or testosterone.
The steroidogenic properties of a steroid hormone-producing tumor were described. Cells isolated from this tumor produced steroids similar to those secreted by ovarian theca cells. These properties suggest that certain ovarian steroidogenic tumor cells may be an appropriate model for ovarian theca cells and could be used to develop steroid-secreting cell lines.
确定卵巢类固醇分泌性支持-间质细胞瘤中类固醇生成谱和类固醇生成酶的定位。
测量外周血、左侧卵巢（肿瘤）和右侧卵巢静脉血中的类固醇水平。通过免疫组织化学检查肿瘤组织中的类固醇生成酶17α-羟化酶（P450c17）和3β-羟类固醇脱氢酶（3βHSD）。分离肿瘤细胞并在无血清培养基中培养。此后，分析培养基中的类固醇生成、效应器对类固醇生成的反应以及放射性标记孕烯醇酮和雄烯二酮的代谢。
外周血中C19类固醇和17-羟孕酮（17OHP）水平升高。左侧卵巢静脉（肿瘤）血清中的大多数（80%）类固醇为C19类固醇（脱氢表雄酮[DHEA]，45%；雄烯二酮，27%，睾酮，7%，17OHP为13%，孕酮为7%，雌二醇（E2）低于1%）。在由组成索状结构的非免疫反应性细胞包围的大细胞簇中鉴定出P450c17和3βHSD的免疫反应性。在未刺激的新鲜分离肿瘤细胞的孵育培养基中积累的类固醇中，84%为C19类固醇（DHEA，44%；雄烯二酮36%；睾酮2%，17OHP为16%，孕酮和E2低于1%）。LH或FSH未刺激基础类固醇生成。然而，用福司可林（10μmol/L）、二丁酰环磷腺苷（1mmol/L）或类固醇前体（22-羟胆固醇，1μmol/L；孕烯醇酮，1μmol/L）处理可增加所有测量类固醇的生成。与基础水平相比，福司可林处理使雄烯二酮增加了5倍、DHEA增加了10倍、17OHP增加了40倍。用[3H]孕烯醇酮孵育新鲜分离的细胞表明这些细胞能够将这种C21类固醇前体代谢为雄烯二酮、DHEA和17OHP。然而，[3H]雄烯二酮不容易被这些细胞代谢为雌酮或睾酮。
描述了一种产生类固醇激素的肿瘤的类固醇生成特性。从该肿瘤分离的细胞产生的类固醇类似于卵巢卵泡膜细胞分泌的类固醇。这些特性表明某些卵巢类固醇生成肿瘤细胞可能是卵巢卵泡膜细胞的合适模型，可用于开发类固醇分泌细胞系。
