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Organ Distribution and Biological Activity of 125-I-Labelled LH-RH Analogues

  • J. Sandow
  • W. v. Rechenberg
  • G. Jerzabek
  • W. Stoll
  • H. Strecker

Abstract

The high biological activity of certain LH-RH analogues may be due to increased receptor binding and/or reduced enzyme stability. The organ distribution of 125-I-labelled analogues was studied to estimate the in vivo degree of receptor binding and the inactivating tissues. The following peptides were labelled with 125-I by the chloramine-T method: LH-RH(1–9) nonapeptide-ethylamide, [D-Glu6] LH-RH(1–9) nonapeptide-ethylamide, [D-Ser(But)6] LH-RH(1–9) nonapeptide-ethylamide and the corresponding (3–9) heptapeptide fragment. Biological activity was tested in ovariectomized, steroid-blocked rats by LH-release. Organ distribution was determined 15, 30 and 60 minutes after iv-injection of labelled peptides. After iodination, biological activity was retained to 30–50%. The order of potency of the labelled analogues was LH-RH: LH-RH(1–9) EA:[D-Glu6]LH-RH(1–9)EA:[D-Ser (But)6]EA = 1:2:20:40. Pituitary accumulation of the weak analogue LH-RH(1–9) EA was only found after 15 minutes (tissue/plasma ratio 1.23), [D-Glu6]LH-RH(1–9) EA reached a T/P ratio of 1.33 after 30 minutes and the highly active [D-Ser(But)6] LH-RH(1–9) EA reached high pituitary accumulation even after 60 minutes (T/P ratio 2.33). The peptides were also concentrated in liver and kidney, the main inactivating organs fop LH-RH. The (3–9) heptapeptide fragment of [D-Ser(But)6] LH-RH(1–9)EA did not show pituitary accumulation, even though it had some residual LH releasing activity.

Keywords

Insulin Release Renin Angiotensin System High Biological Activity Label Peptide Organ Distribution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer-Verlag Berlin Heidelberg 1978

Authors and Affiliations

  • J. Sandow
    • 1
  • W. v. Rechenberg
    • 1
  • G. Jerzabek
    • 1
  • W. Stoll
    • 1
  • H. Strecker
    • 1
  1. 1.Hoechst AG.623 Frankfurt 80Germany

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