Circulating bioactive and immunoreactive recombinant human follicle stimulating hormone (Org 32489) after administration to gonadotropin-deficient subjects

Abstract

Objective: To study the bioactivity of recombinant and urinary human FSH after single IM injection into gonadotropin-deficient subjects.

Design: Serum FSH levels were measured by immature rat granulosa cell bioassay and immuno-fluorometric assay. The isohormone distributions of injected FSH materials were analyzed by chromatofocusing. Serum samples were collected before, and 6, 24, and 72 hours after 300 IU of recombinant or urinary FSH.

Volunteers: Fifteen gonadotropin-deficient subjects (8 women and 7 men) received recombinant FSH and 8 of them (4 women and 4 men) received an equal dose of urinary FSH.

Results: No significant differences were apparent between the bioactive FSH levels after recombinant and urinary FSH treatments (n = 8). The immunoreactive FSH levels at 72 hours after urinary FSH were significantly higher than after recombinant FSH injection with values (median and range) of 3.80 (2.76 to 5.75) IU/L (IRP 78/549) and 3.10 (1.78 to 4.95) IU/L, respectively. There were no significant changes in the bioactive to immunoreactive ratios of FSH within time and between sexes after either recombinant FSH (n = 15) or urinary FSH (n = 8). However, the bioactive to immunoreactive ratio of the FSH material injected and of the post-treatment serum samples were both higher after recombinant FSH than after urinary FSH injection. Chromatofocusing revealed that injected recombinant FSH contained more activity in the basic fractions than urinary FSH.

Conclusion: Recombinant human FSH maintains its biological activity when injected into gonadotropin-deficient subjects. The bioactive to immunoreactive ratio of recombinant FSH was higher than that of urinary FSH indicating that recombinant FSH contains relatively more basic isohormones, and this finding was strengthened by chromatofocusing.