van Noort M, Rommerts F F, van Amerongen A, Wirtz K W
Department of Biochemistry (Division of Chemical Endocrinology), Erasmus University Rotterdam, The Netherlands.
Mol Cell Endocrinol. 1988 Mar;56(1-2):133-40. doi: 10.1016/0303-7207(88)90017-2.
The rate-determining step in steroidogenesis is the conversion of cholesterol to pregnenolone by the cholesterol side-chain cleavage enzyme. The transport of substrate for this reaction may be facilitated by sterol carrier protein2 (SCP2). In rat testis tissue SCP2 is specifically localized in the Leydig cells and tissue levels of SCP2 are regulated by luteinizing hormone (LH). The present study concerns short-term regulation of SCP2 in isolated rat Leydig cells. Levels of SCP2 in the membrane-free supernatant are increased 2-fold already after 2 min incubation with LH and remain elevated for 24 h. The same response occurs with cells preincubated in the presence of cycloheximide for 4 h. SCP2 levels are also 2-fold increased after incubation with dibutyryl cAMP or 4 beta-phorbol 12-myristate 13-acetate (PMA) whereas these compounds stimulate steroid production 5.5- and 2-fold respectively. Luteinizing hormone releasing hormone (LHRH), which can stimulate steroid production more than 3-fold, does not influence SCP2 levels, neither are SCP2 levels altered when LH is added in the presence of the Ca2+-channel blocker diltiazem or in the absence of extracellular Ca2+. A restoration of the LH effect on SCP2 levels was already obtained in the presence of 1 microM extracellular Ca2+. These results suggest that Ca2+ influx through the plasma membrane may play an important role in the control of SCP2 levels. In most of the experiments no correlation between steroid production and SCP2 levels could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
类固醇生成过程中的限速步骤是胆固醇侧链裂解酶将胆固醇转化为孕烯醇酮。固醇载体蛋白2（SCP2）可能会促进该反应底物的转运。在大鼠睾丸组织中，SCP2特异性定位于睾丸间质细胞，且SCP2的组织水平受黄体生成素（LH）调节。本研究关注分离的大鼠睾丸间质细胞中SCP2的短期调节。与LH孵育2分钟后，无膜上清液中SCP2的水平就增加了2倍，并在24小时内保持升高。在放线菌酮存在下预孵育4小时的细胞也出现同样的反应。与二丁酰环磷腺苷或4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）孵育后，SCP2水平也增加了2倍，而这些化合物分别刺激类固醇生成5.5倍和2倍。促黄体生成素释放激素（LHRH）可刺激类固醇生成超过3倍，但不影响SCP2水平；当在钙离子通道阻滞剂地尔硫䓬存在下或无细胞外钙离子时添加LH，SCP2水平也不会改变。在存在1微摩尔细胞外钙离子的情况下，LH对SCP2水平的影响已恢复。这些结果表明，通过质膜的钙离子内流可能在SCP2水平的控制中起重要作用。在大多数实验中，未观察到类固醇生成与SCP2水平之间的相关性。（摘要截短于250字）
