DISCORDANT LEVELS OF SERUM BIOACTIVE LH IN MAN AS MEASURED IN DIFFERENT INVITRO BIOASSAY SYSTEMS USING RAT AND MOUSE INTERSTITIAL-CELLS AND HUMAN GRANULOSA-LUTEAL CELLS

Serum samples from healthy men (n = 6), perimenopausal women (n = 9) and patients with polycystic ovarian disease (n = 4) were analysed for LH bioactivity by the two widely used in-vitro bioassay systems: the mouse and rat interstitial cell testosterone-formation assays. The results were compared with an assay employing LH-stimulated cyclic AMP production by cultured human granulosa-luteal cells. Average bioactive LH levels in the mouse cell assay were 1.6-fold higher than those measured using the rat assay. A good correlation (r = 0.89, P < 0.01) was observed between the bioactive LH levels measured by these two assays. No significant difference was found between the sensitivities of the two assays: 0.009+/-0.003 IU/l (mean +/- S.E.M., n = 10) with rat cells and 0.011 +/- 0.003 IU/l (n = 10) with mouse cells. The LH level resulting in half-maximal stimulation of testosterone production in the mouse model was twofold higher than that in the rat model (0.185 +/- 0.020 vs 0.083 +/- 0.022 IU/l, P < 0.01). The bioactive LH levels measured by the human granulosa-luteal cell assay averaged 12% higher than those obtained with the rat assay (r = 0.84, P < 0.01), but 58% lower than levels measured with the mouse assay (r = 0.86, P < 0.01). The data indicate that the target cell model used in the in-vitro bioassay of LH contributes to the documented discrepancies in reports on serum levels of bioactive LH. Although good correlations were found between all assay systems, the absolute levels of LH bioactivity measured with the rat assay are closer than mouse data to levels measured with a homologous bioassay employing human granulosa-luteal cells.