CHANGES IN THE KINETICS AND BIOPOTENCY OF LUTEINIZING-HORMONE IN HEMODIALYZED MEN DURING TREATMENT WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals. The ratio of bioactive to immunoreactive LH increased under rh-EPO from 2.0 +/- 0.6 to 2.7 +/- 0.5 (P = 0.05), indicating greater biopotency of the circulating hormone. In contrast to basal bio-LH production, the GnRH-stimulated production rate, an index of the maximal secretory capacity of the gonadotroph, was similar before and after rh-EPO (33 +/- 6.3 versus 29 +/- 7.9 IU/L per hour). In conclusion, rh-EPO treatment causes a distinct decrease in the plasma half-life of bio-LH and a quantitative and qualitative increase in LH signal strength delivered to the target tissue as a result of a greater secretory burst mass, incremental plasma pulse amplitude, and relative biopotency.