Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin

Franz Schaefer, Birgit Van Kaick, Johannes D Veldhuis, Günter Stein, Karl Schärer, William R. Robertson, Eberhard Ritz

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1208-1215
Number of pages8
JournalJournal of the American Society of Nephrology
Volume5
Issue number5
StatePublished - Nov 1994
Externally publishedYes

Keywords

  • Erythropoietin
  • Hormone kinetics
  • Luteinizing hormone
  • Uremia

ASJC Scopus subject areas

  • Nephrology

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