Evidence for the Existence of a Large Molecular Weight Protein in Human Pituitary Tissue Having Follicle Stimulating Hormone Activity

Abstract

A large molecular weight protein fraction was isolated during purification of follicle stimulating hormone (hFSH) from acetone preserved human pituitary glands. This large molceular weight fraction, F-l, was not retarded by Sephadex G-100 as was hFSH, nor did it penetrate 7.% acrylamide gel upon electrophoresis in sodium dodecyl sulfate as did hFSH. There was no evidence of dissociation of F-l into smaller molecular weight fractions upon its refiltration through Sephadex G-100 or upon electrophoresis, suggesting F-l was not an aggregate of smaller size proteins. Fraction F-l stimulated ovarian growth in rats, inhibited binding of ¹²⁵I-hFSH to rat testes membranes and cross-reacted with antiserum to hFSH, hFSH-alpha subunit and hFSH-beta subunit as determined by radioimmunoassay. Based on gel filtration experiments, it seemed unlikely that immunologic activity against subunit antisera could be attributed to contamination of F-l by free FSH subunits. The membrane binding activity of F-l decreased after incubation with 8M urea, but at a rate less than ½ that seen with intact hFSH similarly treated, indicating the two activities were not identical. These results suggest that human pituitary tissue contains a large molecular weight protein with FSH-like biologic and immunologic activity, but which is distinct from native hFSH.