Expression of biologically active human follitropin in Chinese hamster ovary cells

To study the structure-function relationships of follitropin (FSH), we expressed the hormone in a heterologous cell system. A genomic clone bearing a 3.7-kilobase FSHβ insert containing the entire coding sequence was transfected alone or together with the α subunit gene into Chinese hamster ovary cells and stable lines expressing either FSHβ or FSH dimer were selected. Pulse-chase experiments revealed that, when transfected alone FSHβ was very slowly secreted similar to lutropin β and thyrotropin β but unlike choriogonadotropin β which is efficiently secreted. However, cotransfection of the FSHβ and α subunit genes resulted in 'rescue' of the β subunit and rapid secretion of dimer. These data support the hypothesis that the glycoprotein hormones of pituitary origin have determinants for secretion that differ from those on the placental hormone, choriogonadotropin. Recombinant FSH stimulated steroidogenesis comparable to purified human FSH isolated from pituitaries in an in vitro rat granulosa cell assay and appears more homogeneous by chromatofocusing. Human FSH produced by this cell line provides a source of bioactive FSH for experimental and clinical use.