Mammalian follistatin

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Glycoprotein – e.g. – mucins – proteoglycans – etc.

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Details

530397, 530387, 530350, C07K 1300

Patent

active

050415387

ABSTRACT:
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 NH.sub.2 -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.

REFERENCES:
patent: 4624944 (1986-11-01), Li et al.
Shimasaki et al., Porcine Follistatin Gene Structure Supports Two Forms of Mature Follistatin, Biochem & Biophys. Res. Comm 152(2) 717-723 (1988).
diZerega et al., "Identification of Protein(s) Secreted by the Preovulatory Ovary which Suppresses the Follicle Response to Gonadotropins," J. Clin. Endocrinol. and Metab., 54: 1091-1096 (1982).
Kling et al., "Identification of Procine Follicular Fluid Fraction which Suppresses Follicular Response to Gonadotropins," Biology of Reproduction, 30: 564-572 (1984).
Mason et al., "Complementary DNA Sequences of Ovarian Follicular Fluid Inhibin Show Precursor Structure and Homology with Transforming Growth Factor-.beta.," Nature, 318: 659-663 (1985).
Mason et al., "Structure of Two Human Ovarian Inhibins,"0 Biochem. & Biophys. Res. Commun., 135: No. 3, 957-964 (1986).
Forage et al., "Cloning and Sequence Analysis of cDNA Species Coding for the Two Subunits of Inhibin from Bovine Follicular Fluid," Proc. Natl. Acad. Sci. U.S.A., 83: 3091-3095 (1986).

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