公开(公告)号：EP0377659B1

公开(公告)日：1994-11-02

申请号：EP88908558.5

申请日：1988-08-26

申请人： THE SALK INSTITUTE FOR BIOLOGICAL STUDIES

发明人： LING, Nicholas, Chai-Kwan ,  UENO, Naoto, Assistant Professor, Institute for ,  SHIMASAKI, Shunichi ,  ESCH, Frederick, Steven ,  YING, Shao-Yao ,  GUILLEMIN, Roger, Charles, Louis

IPC分类号： C12N15/16 ,  C07K15/06 ,  C07H21/04

CPC分类号： C07K14/4703 ,  C07K14/575

摘要： Two follistatin proteins with inhibin-like activity were isolated from porcine follicular fluid using heparin-Sepharose affinity chromatography, followed by gel filtration on Sephacryl S-200 and then six steps of high-performance liquid chromatography. Each isolated molecule is a monomer having a molecular weight of at least about 32,000 daltons. Microsequencing revealed the NH2-terminal portions both to be Gly-Asn-Cys-Trp-Leu-Arg-Gln-Ala-Lys-Asn-Gly-Arg-Cys-Gln-Val-Leu. The larger protein has 315 residues and is believed to be glycosylated. The smaller protein is a 288-residue, C-terminally shortened version thereof. These proteins specifically inhibit basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system. The half-maximal effective dose for both is 2.5-6.0 ng/ml. Human and rat follistatins exhibit very high homology with the porcine protein, with the human differing from porcine in only 4 residues out of 315 and with the rat differing from porcine in only 8 residues out of 315.