Molecular heterogeneity of serum follicle-stimulating hormone in hypogonadal patients before and during androgen replacement therapy and in normal men

OBJECTIVE The present study was performed to characterize the molecular heterogeneity of serum FSH in normal males and to investigate the possible influence of testosterone on serum FSH in androgen-deficient men before and during testosterone administration. DESIGN AND PATIENTS Serum samples were taken at 10-minute intervals between 0730 and 0830 h from nine healthy, eugonadal men and from eight men with primary hypogonadism (Klinefelter's syndrome). In the hypogonadal patients, sampling was performed before treatment (n= 8), 4-5 days after the first and the third injection of 250 mg testosterone enanthate given intramuscularly at three-weekly intervals (n= 6), as well as 3 months after the onset of therapy (n= 3). Sampling was repeated 7 days apart in two of the nine healthy volunteers. MEASUREMENTS Aliquots from the individual serum samples were pooled and fractionated by chromatofocusing in the pH range 6-3. Immunoreactive FSH was measured by immunofluorimetric assay (IFMA) in each fraction and the individual serum samples. In each serum pool, bioactive FSH was determined by in-vitro bioassay (rat Sertoli cell aromatase bioassay), testosterone by RIA and LH by IFMA. RESULTS After grouping the percentage of immunoreactive FSH recovered in the individual fractions into intervals of 0 5 pH units, significant differences between controls and patients were observed in the pH regions 4-4.5, 5.5-6 and 6-6.5. No statistically significant changes in the isoform distribution of FSH were detected during therapy in the Klinefelter patients. A high degree of variability, which did not follow a common pattern, was observed in the isoform distribution of FSH within the same individuals, both in the hypogonadal patients during treatment and in the two normal men whose blood samples were taken on two different occasions. CONCLUSIONS Serum FSH is highly heterogeneous in normal and hypogonadal men. There is a spontaneous intra-individual variability in the relative abundance of the different FSH isoforms in serum that may most probably be related to metabolic deglycosylation of FSH. Minor but significant differences in the molecular heterogeneity of serum FSH could be demonstrated in Klinefelter patients compared to normal men. These differences are not modified by administration of testosterone enanthate at doses achieving normal androgenization, suggesting that factors different from testosterone may modulate FSH pleomorphism.