Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testes. Leydig cells can synthesize testosterone and are often closely related to nerves. Leydig cells have round vesicular nuclei and a granular eosinophilic cytoplasm. Leydig cells are named after Johannes Leydig, who discovered them in 1850.

3 beta-HSD (3 -hydroxysteroid dehydrogenase, 3b-HSD)

• Leydig cell marker gene. PMID: 9369931
• one of the key enzymes involved in the steroidogenic pathway of Leydig cells. PMID: 7947353
• 3beta-HSD reactivity was located at subcellular levels by means of the ferricyanide method. A specific, distinct localization of reaction product in the form of copper ferrocyanide precipitates was observed on the membranes of the smooth endoplasmic reticulum not only in the fetal-type Leydig cells and the fibroblast-like precursors of adult-type Leydig cells, but also focally in the endothelial cells of interstitial blood capillaries. PMID: 9725769
• These data show very early immunoexpression of 3beta-HSD, which was detected one day before the reported start of steroid production by the fetal Leydig cells. PMID: 9475409
• localized on the tubular or lamellar cristae and inner membranes of the mitochondria, and on the membranes of smooth endoplasmic reticulum in the transitional cell as well as in the Leydig cell. PMID: 6584387
• Immunohistochemical studies revealed that the Leydig cell tumor contained testosterone, estrogens, and 17 beta-hydroxysteroid dehydrogenase (HSD) in the cytoplasm. This is the first report of a Leydig cell tumor in which the localization of 17 beta-HSD was demonstrated immunohistochemically. PMID: 2707954

7-dehydrocholesterol reductase (7-DHCR)

• a key marker of early Leydig cell steroidogenesis. PMID: 15149725

11 beta-hydroxysteroid dehydrogenase

• type I 11betaHSD is a predominant oxidase in Leydig cells in vivo. PMID: 10714825
• a marker for Leydig cell maturation in rat. PMID: 2080241

Calretinin

• a valuable marker of normal and neoplastic Leydig cells of the testis. PMID: 12051635, PMID: 12409718, PMID: 10886732
• Leydig cells in all the assessed biopsies expressed calretinin and served as a built-in control for immunoreactivity. PMID: 15950053
• In normal canine testis, calretinin expression was restricted to Leydig and Sertoli cells of the testis. In tumour tissues, calretinin expression was detected in all tumours investigated (interstitial cell tumours, seminoma, and Sertoli cell tumours), with a cytoplasmic and nuclear pattern of cellular distribution. PMID: 15924929
• In normal tissues, a particularly strong expression was found in Leydig cells of the testis, neurons of the brain, theca-lutein and theca interna cells of the ovary, and mesothelium. PMID: 14608532
• In postpubertal testes, calretinin was expressed in Leydig cells, but not in germ cells or most rete testes and Sertoli cells. The expression of calretinin in normal Leydig cells, theca interna cells, the Leydig cell component of Sertoli-Leydig cell tumors, and hilus cell tumors suggests its functional relationship with androgen production. PMID: 11603218

Cyp17 and Cyp11a1

• fetal Leydig cell markers. PMID: 12193547

Esterase

• a useful marker enzyme for Leydig cells from mature rats and can be of help in studies concerning the development of these cells. PMID: 3457892, PMID: 7172178

Inhibin-alpha

• a Leydig cell marker. PMID: 12409718, PMID: 10886732
• normal Leydig cells secrete inhibin alpha-subunits, while Leydig cell tumors can also secrete bioactive inhibin. Neither normal Leydig cells nor Leydig cell tumors produce activin. PMID: 1547906
• Leydig cells express mRNA for the alpha-subunit of inhibin and produce inhibin which is biologically and immunologically active prompting a re-evaluation of our concepts of testicular inhibin production. PMID: 2511047

IGF-1 (insulin like growth factor-1)

• acts subsequently in the transformation of immature Leydig cells into adult Leydig cells. PMID: 7626518

INSL3 (Insulin-like factor 3)

• expressed exclusively in prenatal and postnatal Leydig cells is increasingly used as a specific marker of Leydig cell differentiation and function. PMID: 8020942
• a hormone produced by testicular Leydig cells throughout life. PMID: 16467267
• a major new product of the Leydig cells in all mammalian species so far examined. PMID: 16006031
• the postpubertal Leydig cell marker. PMID: 15151926
• highly expressed in the fetal and adult-type Leydig cells of all species so far examined. PMID: 12559415

Ley I-L (Leydig insulin-like gene)

• a member of the insulin-related gene family, is specifically expressed in pre- and postnatal Leydig cells of the testis and in postnatal theca cells of the ovary. PMID: 9605933

LRH-1 (liver receptor homolog-1)

• expressed in adult rat and immature mouse Leydig cells (LHR-1 > SF-1) as well as in pachytene spermatocytes and round spermatids but not in Sertoli cells. PMID: 14736734

Luteinizing Hormone (LH) receptor

• a specific Leydig cell marker. PMID: 7956896, PMID: 1505454, PMID: 3680291

Melan-A

• a Leydig cell marker. PMID: 12409718
• Melan-A/MART-1 antigen is also expressed in Leydig cells, adrenal tissue, and steroid-secreting tumors. PMID: 12966351
• nuclear staining was also frequently seen in normal Leydig cells and their tumors. PMID: 11478605

Nestin

• expressed in a population of normal and hyperplastic Leydig cells and in Sertoli cells in the presence of intratubular germ-cell neoplasia. PMID: 15127288
• a marker of the Leydig cell progenitors. PMID: 15569711

Neuron-Specific Enolase (NSE)

• Using the peroxidase anti-peroxidase immunocytochemical technique, neuron-specific enolase (NSE)-like immunoreactivity (NSE-LI) was revealed in Leydig cells of adult human testes at the light microscopic level. PMID: 1772141

P450arom (cytochrome P450 aromatase)

• aromatase activity has been measured in immature and mature rat Leydig cells as well as in Sertoli cells, whereas in the pig, ram and human aromatase is mainly present in Leydig cells. PMID: 10442293

PBR (Peripheral-type benzodiazepine receptor)

• an 18-kDa high-affinity cholesterol and drug ligand-binding protein involved in many cellular functions, including steroidogenesis, oxidative processes, cellular proliferation, and apoptosis. PBR mRNA were also observed in the steroid-synthesizing MA-10 mouse Leydig tumor cells. PMID: 14630713, PMID: 12388644
• plays critical roles in age-related decreases in testosterone production in Brown Norway rat Leydig cells. PMID: 12002446
• an Mr 18,000 protein primarily localized to the mitochondria, mediates cholesterol transport across the mitochondrial membranes in steroidogenic cells. PMID: 10029072
• an outer mitochondrial membrane protein involved in the regulation of cholesterol transport from the outer to the inner mitochondrial membrane, the rate-determining step in steroid biosynthesis. PMID: 9832438
• the 18-kDa PBR may have a more important role in steroidogenesis than in proliferation in this Leydig cell line. PMID: 9488670

Relaxin-like factor (RLF)

• a new marker for Leydig cell maturation. PMID: 10330103
• a highly specific and constitutive new marker for Leydig cells in the human testis. PMID: 9239733
• also known as the Leydig cell insulin-like factor (Ley-I-L), is a novel member of the insulin-IGF-relaxin family of hormones and growth factors that has recently been shown to be strongly expressed in testicular Leydig cells, and appears to be a useful marker for Leydig cells in the human ovary and may be a diagnostic supplement in hyperplasias and tumors derived therefrom. PMID: 10202675
• new member of the insulin-like growth factor family, is a reliable marker for normal Leydig cells in the human postpubertal testis. PMID: 10519633

SCC (P450 side-chain cleavage enzyme)

• a marker of fetal Leydig cell differentiation. PMID: 7669257, PMID: 11786430, PMID: 10859256

Substance P (SP)

• Substance P(SP)-like immunoreactivity (-LI) was found to be present in both fetal and adult generation of Leydig cells in hamster and guinea pig, while neuron-specific enolase (NSE)-LI was detected in Leydig cells of the 3 species at all stages studied. PMID: 1725082

STAR (steroidogenic acute regulatory protein)

• an important Leydig cell cholesterol transfer protein, is a Leydigcell-specific marker. PMID: 11384875, PMID: 15611563, PMID: 11191081

Steroidogenic Factor-1 (SF-1, Nr5a1, and Ad4bp)

• the only transcription factor known to regulate the mouse Insl3 promoter in Leydig cells. PMID: 16467267
• an orphan nuclear receptor required for adrenal and gonad development and endocrine regulation. PMID: 16467257
• an orphan nuclear receptor that is important for expression of genes involved in sexual differentiation, testicular and adrenal development, and hormone synthesis and regulation. PMID: 12390883
• regulated both basal and cAMP-stimulated transcription in mouse adrenocortical and Leydig cells. PMID: 10098601
• plays a key role in regulating the expression of the rat P450c17 gene in testicular Leydig and in adrenocortical cells. PMID: 9178749

Thrombospondin 2 (TSP2)

• the fetal Leydig cell (LC) marker gene, is a fetal Leydig cell marker. PMID: 16007123, PMID: 11906915
• may be expressed only in the fetal Leydig cell population. PMID: 11906915

Other Leydig Cell Markers

• The four markers of adult Leydig cell differentiation which were measured in this study (3βHSD VI, PGD-synthetase, EST and 17βHSD III). PMC 151561
• Changes in Leydig cell gene expression during development in the mouse: These five genes (3beta-hydroxysteroid dehydrogenase (3beta-HSD) VI, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) III, vascular cell adhesion molecule 1, estrogen sulfotransferase, and prostaglandin D (PGD)-synthetase) expressed in the mouse adult Leydig cell population, but not in the fetal population. PMID: 11906915