In-vitro biopotency and glycoform distribution of recombinant human follicle stimulating hormone (Org 32489), Metrodin and Metrodin-HP

In this study the in-vitro biopotency and glycoform distributionof human recombinant follicle stimulating hormone (FSH, Org32489) has been assessed. The biopotency of recombinant FSHwas studied using animal (rat Sertoli) and human (granulosa-lutein)cell models. Recombinant FSH, as measured in the rat Sertolicell assay, was more potent than the urinary preparations Metrodin,Metrodin-HP and IS 70/45 with half maximal stimulation (ED₅₀;mean ± SEM, n 3) occurring at 2.2 ± 0.5 IU/I (recombinantFSH), 4.7 ± 1.1 IU/I (Metrodin), 13.2 ± 0.7 IU/I(Metrodin-HP) and 6.4 ± 0.3 IU/I (IS 70/45); the pituitarypreparation IRP 83/575 had an EDM of 10.4 ± 0.1 IU/I.Using human granulosa-lutein cells, cultured for up to 4 daysin the absence of exogenous steroid precursors, recombinantFSH was either without effect (three out of five patients) orinhibited both oestradiol and progesterone secretion. FSH (83/575)was without effect on oestradiol with preparations from anyof the patients but slightly stimulated (134 ± 8%; mean± SEM, P < 0.05) progesterone production at the highestdose (80 IU/I). The distribution of FSH isoforms, assessed bypolyclonal radioimmunoassay, following chromatofocusing overthe ranges pH < 3.5 and pH 3.5–7.0 respectively wasrecombinant FSH, 12.4 and 87.6%; Metrodin, 19.8 and 80.2%; Metrodin-HP,50.2 and 49.8%; IS 70/45, 15.0 and 85.0%; IS 83/575, 70.9 and29.1%. All glycoforms were pi <7.0 for the five preparations.In conclusion: (i) the potency of FSH as measured in the ratSertoli cell assay increases in the order Metrodin-HP < pituitaryIRP 83/575 < < Metrodin < IS 70/45 < recombinantFSH; (ii) in contrast to 83/575, recombinant FSH inhibits steroidogenesisin human granulosa-lutein cells isolated from some patients;(iii) the glycoform distribution of recombinant FSH resemblesMetrodin more closely than Metrodin-HP which is far more acidicin nature. biopotency/glycoform/isoform/Metrodin/recombinant FSH