Localization of the Steroidogenic Acute Regulatory Protein in Human Tissues1

• Published in: The journal of clinical endocrinology and metabolism Vol. 82; no. 12; pp. 4243 - 4251
• Main Authors: Pollack, Staci E, Furth, Emma E, Kallen, Caleb B, Arakane, Futoshi, Kiriakidou, Marianthi, Kozarsky, Karen F, Strauss, Jerome F
• Format: Journal Article
• Language: English; Japanese
• Published: Endocrine Society 01-12-1997
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.82.12.4445

The rate-limiting step in steroid hormone production in the adrenal
cortex and gonads, the translocation of cholesterol from the outer to
the inner mitochondrial membranes, is mediated by the steroidogenic
acute regulatory protein (StAR). Heretofore, the localization of StAR
in human adult and fetal tissues has not been defined. To this end,
expression of StAR was detected in formalin-fixed, paraffin-embedded
specimens using a polyclonal antiserum raised against recombinant human
StAR.
Primordial follicles of adult ovaries did not contain StAR,
whereas antral follicles stained intensely in the thecal layer, with
occasional staining of granulosa cells. Corpora lutea were intensely
stained, but with a patchy distribution. Corpora albicantia did not
stain. A luteoma of pregnancy stained with patches of moderate
intensity. Ovaries with hyperthecosis contained areas of intense thecal
staining. An ovarian 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 immunostaining. 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. There was minimal to
moderate staining in the adrenal glomerulosa and faciculata and minimal
staining in the reticularis, while the medulla was negative. Adrenal
cortical adenomas, hyperplasias, and carcinomas all contained areas of
StAR staining. The renal distal tubules stained with moderate to marked
intensity. Renal carcinomas had occasional modest staining.
No immunostaining was found in the placenta. Fetal ovaries contained
sporadic stromal cells displaying intense StAR staining, particularly
in the hilar region. Oocytes from a 32-week fetal ovary showed moderate
to intense staining. Fetal testes displayed intense Leydig cell
staining. The neocortex of the fetal adrenal glands displayed only
minimal StAR staining, whereas moderate to intense staining was found
in the fetal zone. The fetal kidneys had moderate StAR staining of the
distal convoluted tubules.
We conclude that StAR is localized to normal and neoplastic cells
in the gonads and adrenal cortex, which produce large amounts of
pregnenolone. StAR protein was not detected in the placenta,
documenting that placental progestin synthesis occurs through
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,
suggests that StAR has roles in metabolic processes in addition to
stimulating pregnenolone synthesis.