LOCALIZATION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN IN HUMAN TISSUES

The rate-limiting step in steroid hormone production in the adrenal co rtex and gonads, the translocation of cholesterol from the outer to th e inner mitochondrial membranes, is mediated by the steroidogenic acut e regulatory protein (StAR). Heretofore, the localization of StAR in h uman adult and fetal tissues has not been defined. To this end, expres sion of StAR was detected in formalin-fixed, paraffin-embedded specime ns using a polyclonal antiserum raised against recombinant human StAR. Primordial follicles of adult ovaries did not contain StAR, whereas a ntral follicles stained intensely in the thecal layer, with occasional staining of granulosa cells. Corpora lutea were intensely stained, bu t with a patchy distribution. Corpora albicantia did not stain. A lute oma of pregnancy stained with patches of moderate intensity. Ovaries w ith hyperthecosis contained areas of intense thecal staining. An ovari an Leydig cell tumor stained intensely, whereas granulosa cell tumors were negative. Ovarian adenocarcinomas, borderline tumors, teratomas, cystadenomas, and a Brenner tumor displayed no specific StAR immunosta ining. Testicular Leydig cells stained moderately to intensely, as did a testicular Leydig cell tumor. Sertoli cells stained weakly in some specimens. Seminomas and testicular germ cell tumors were negative. Th ere was minimal to moderate staining in the adrenal glomerulosa and fa ciculata and minimal staining in the reticularis, while the medulla wa s negative. Adrenal cortical adenomas, hyperplasias, and carcinomas al l contained areas of StAR staining. The renal distal tubules stained w ith moderate to marked intensity. Renal carcinomas had occasional mode st staining. No immunostaining was found in the placenta. Fetal ovarie s contained sporadic stromal cells displaying intense StAR staining, p articularly in the hilar region. Oocytes from a 32-week fetal ovary sh owed moderate to intense staining. Fetal testes displayed intense Leyd ig cell staining. The neocortex of the fetal adrenal glands displayed only minimal StAR staining, whereas moderate to intense staining was f ound in the fetal zone. The fetal kidneys had moderate StAR staining o f the distal convoluted tubules. We conclude that StAR is localized to normal and neoplastic cells in the gonads and adrenal cortex, which p roduce large amounts of pregnenolone. StAR protein was not detected in the placenta, documenting that placental progestin synthesis occurs t hrough StAR-independent mechanisms. The presence of StAR in cells that do not express cholesterol side-chain cleavage enzyme cytochrome P450 , including renal distal tubules, Sertoli cells, and fetal oocytes, su ggests that StAR has roles in metabolic processes in addition to stimu lating pregnenolone synthesis.