Identification of a Stimulator of Steroid Hormone Synthesis Isolated from Testis

• Published in: Science (American Association for the Advancement of Science) 1995-06, Vol.268 (5217), p.1609-1612
• Main Authors: Boujrad, Noureddine, Ogwuegbu, Stephen O., Garnier, Martine, Lee, Choong-Hyu, Martin, Brian M., Papadopoulos, Vassilios
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Antiserum; Biological and medical sciences; Cathepsin L; Cathepsins - chemistry; Cathepsins - isolation & purification; Cathepsins - pharmacology; Cathepsins - physiology; Cells, Cultured; Cellular biology; Complementary DNA; Culture Media, Conditioned; Cultured cells; Cyclic AMP - metabolism; Enzyme Precursors - chemistry; Enzyme Precursors - isolation & purification; Enzyme Precursors - pharmacology; Enzyme Precursors - physiology; Enzymes; Female; Follicle Stimulating Hormone - pharmacology; Fractions; Fundamental and applied biological sciences. Psychology; Germ cells; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - isolation & purification; Glycoproteins - pharmacology; Glycoproteins - physiology; Granulosa cells; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Hormone metabolism and regulation; Hormones; Hormones, Sex; Individualized Instruction; Leydig cells; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; Mammalian male genital system; Molecular Sequence Data; Molecular Weight; Physiological aspects; Pregnenolone - biosynthesis; Progesterone - biosynthesis; Protein hormones. Growth factors. Cytokines; Proteins; Rats; Rats, Sprague-Dawley; Seminiferous tubules; Sertoli cells; Sertoli Cells - chemistry; Sex hormones; Sexes; Steroid hormones; Steroidogenesis; Steroids; Tissue Inhibitor of Metalloproteinases; Transfection; Vertebrates: reproduction
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7777858

Gonadal steroidogenesis is regulated by pituitary gonadotropins and a locally produced, unidentified factor. A 70-kilodalton (kD) protein complex secreted from rat Sertoli cells was isolated. The complex, composed of 28- and 38-kD proteins, stimulated steroidogenesis by Leydig cells and ovarian granulosa cells in a dose-dependent and adenosine 3′,5′-monophosphate-independent manner. The follicle-stimulating hormone-induced 28-kD protein appeared to be responsible for the bioactivity, but the 38-kD protein was indispensable for maximal activity. The 28- and 38-kD proteins were shown to be identical to the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the proenzyme form of cathepsin L, respectively. Thus, a TIMP-1-procathepsin L complex is a potent activator of steroidogenesis and may regulate steroid concentrations and, thus, germ cell development in both males and females.