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 journalArticle

21 Citations (Scopus)

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

Fingerprint

Luteinizing Hormone
Erythropoietin
Therapeutics
Hormones
Half-Life
Gonadotropin-Releasing Hormone
Erythrocyte Volume
Gonadotrophs
Immunoradiometric Assay
Leydig Cells
Hematocrit
Biological Assay
Chronic Kidney Failure
Anemia
Erythrocytes

Keywords

  • Erythropoietin
  • Hormone kinetics
  • Luteinizing hormone
  • Uremia

ASJC Scopus subject areas

  • Nephrology

Cite this

Schaefer, F., Van Kaick, B., Veldhuis, J. D., Stein, G., Schärer, K., Robertson, W. R., & Ritz, E. (1994). Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin. Journal of the American Society of Nephrology, 5(5), 1208-1215.

Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin. / Schaefer, Franz; Van Kaick, Birgit; Veldhuis, Johannes D; Stein, Günter; Schärer, Karl; Robertson, William R.; Ritz, Eberhard.

In: Journal of the American Society of Nephrology, Vol. 5, No. 5, 11.1994, p. 1208-1215.

Research output: Contribution to journalArticle

Schaefer, F, Van Kaick, B, Veldhuis, JD, Stein, G, Schärer, K, Robertson, WR & Ritz, E 1994, 'Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin', Journal of the American Society of Nephrology, vol. 5, no. 5, pp. 1208-1215.
Schaefer, Franz ; Van Kaick, Birgit ; Veldhuis, Johannes D ; Stein, Günter ; Schärer, Karl ; Robertson, William R. ; Ritz, Eberhard. / Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin. In: Journal of the American Society of Nephrology. 1994 ; Vol. 5, No. 5. pp. 1208-1215.
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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.",
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