Analysis of the Cys82Arg mutation in follicle-stimulating hormone beta (FSHβ) using a novel FSH expression vector

Objective: To determine the effect of the Cys82Arg FSHβ mutation from a patient with isolated FSH deficiency upon follicle-stimulating hormone (FSH) levels in vitro. Design: In vitro analysis of the Cys82Arg mutation and comparison with the phenotype. Setting: Tertiary medical center setting. Patient(s): DNA sequence of the FSHβ gene and clinical description from a patient with isolated FSH deficiency. Intervention(s): Construction of a new vector containing the cDNAs for the α-subunit and β-subunit of FSH (pαFSHβ) followed by mutagenesis and transfection into Chinese hamster ovary cells. Main Outcome Measure(s): Immunoreactive and bioactive FSH levels from the CHO cellular media. Result(s): Although expression of both subunits was present, both immunoreactive and bioactive FSH levels were unmeasurable from cellular media containing the mutation versus wild type. Conclusion(s): The Cys82Arg mutation in a male with normal puberty and azoospermia results in profound deficiency of FSH in vitro, thereby confirming the molecular basis of hypogonadism in this patient and documenting the importance of the Cys residue at position 82 of the FSHβ subunit.