Identification of a stimulator of steroid hormone synthesis isolated from testis.
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.
Boujrad
N
N
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Ogwuegbu
S O
SO
Garnier
M
M
Lee
C H
CH
Martin
B M
BM
Papadopoulos
V
V
D000595:Amino Acid Sequence; D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D000242:Cyclic AMP / Q000378:metabolism; D004792:Enzyme Precursors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011284:Pregnenolone / Q000096:biosynthesis*; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000737:chemistry*; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection
D017077:Culture Media, Conditioned; D004792:Enzyme Precursors; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D011374:Progesterone; D011284:Pregnenolone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D002403:Cathepsins; C063905:procathepsin L; D056668:Cathepsin L