1991年3月
19-HYDROXYANDROSTENEDIONE DOES NOT MODULATE [H-3] ALDOSTERONE BINDING TO HUMAN MONONUCLEAR LEUKOCYTES AND RAT RENAL CYTOSOL
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
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- 巻
- 38
- 号
- 3
- 開始ページ
- 331
- 終了ページ
- 337
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/0960-0760(91)90104-D
- 出版者・発行元
- PERGAMON-ELSEVIER SCIENCE LTD
To verify the aldosterone amplifying action of 19-hydroxyandrostenedione (19-OH-AD), we investigated [H-3]aldosterone and [H-3]19-OH-AD binding to type I (mineralocorticoid) receptor in the renal cytosol of adrenalectomized and ovariectomized rat, and human mononuclear leucocytes (MNL).
In the [H-3]aldosterone binding study, the cytosol was incubated with [H-3]aldosterone and 200-fold RU28362 (11-beta,17-beta-dihydroxy-6-methyl-,17-alpha-(1-propynyl)-androsta-1,4,6-trien-3-one), a pure glucocorticoid, with or without 19-OH-AD. Scatchard plots of [H-3]aldosterone binding to cytosol with 0.2 or 20 nM 19-OH-AD or without 19-OH-AD were linear. Dissociation constants (K(d)) and maximum bindings (B(max)) without 19-OH-AD, and with 0.2 and 20 nM 19-OH-AD were: 0.71 +/- 0.03 nM and 23.0 +/- 3.4 fmol/mg protein (mean +/- SD, n = 3), 0.72 +/- 0.05 nM and 23.1 +/- 2.3 fmol/mg protein (n = 3), and 0.77 +/- 0.04 nM and 22.9 +/- 4.8 fmol/mg protein (n = 3), respectively. 19-OH-AD did not significantly change the K(d) and B(max) of [H-3]aldosterone binding. A high concentration of 19-OH-AD slightly displaced 0.2 or 5 nM [H-3]aldosterone bound to cytosol. In human MNL, Scatchard plots of [H-3]aldosterone binding with both 0.2 and 20 nM 19-OH-AD and without 19-OH-AD were linear. K(d) and B(max) were, respectively, 1.00 nM and 780 sites/cell in the absence of 19-OH-AD, and 1.07 nM and 774 sites/cell in the presence of 0.2 nM 19-OH-AD. Without 19-OH-AD they were, respectively, 0.95 nM and 551 sites/cell, and 1.10 nM and 560 sites/cell with 20 nM 19-OH-AD. A high concentration of 19-OH-AD slightly displaced 0.2 or 5 nM of [H-3]aldosterone bound to MNL.
In both tissues, there was no obvious specific binding of [H-3]19-OH-AD within the range of 1-60 nM.
The above results suggest that the amplifying effect of 19-OH-AD on aldosterone mineralocorticoid action may not occur at the binding site of aldosterone to type I receptor, and that 19-OH-AD itself may not have any direct or indirect mineralocorticoid actions on the steroid receptor-mediated process in the rat kidney and human MNL.
In the [H-3]aldosterone binding study, the cytosol was incubated with [H-3]aldosterone and 200-fold RU28362 (11-beta,17-beta-dihydroxy-6-methyl-,17-alpha-(1-propynyl)-androsta-1,4,6-trien-3-one), a pure glucocorticoid, with or without 19-OH-AD. Scatchard plots of [H-3]aldosterone binding to cytosol with 0.2 or 20 nM 19-OH-AD or without 19-OH-AD were linear. Dissociation constants (K(d)) and maximum bindings (B(max)) without 19-OH-AD, and with 0.2 and 20 nM 19-OH-AD were: 0.71 +/- 0.03 nM and 23.0 +/- 3.4 fmol/mg protein (mean +/- SD, n = 3), 0.72 +/- 0.05 nM and 23.1 +/- 2.3 fmol/mg protein (n = 3), and 0.77 +/- 0.04 nM and 22.9 +/- 4.8 fmol/mg protein (n = 3), respectively. 19-OH-AD did not significantly change the K(d) and B(max) of [H-3]aldosterone binding. A high concentration of 19-OH-AD slightly displaced 0.2 or 5 nM [H-3]aldosterone bound to cytosol. In human MNL, Scatchard plots of [H-3]aldosterone binding with both 0.2 and 20 nM 19-OH-AD and without 19-OH-AD were linear. K(d) and B(max) were, respectively, 1.00 nM and 780 sites/cell in the absence of 19-OH-AD, and 1.07 nM and 774 sites/cell in the presence of 0.2 nM 19-OH-AD. Without 19-OH-AD they were, respectively, 0.95 nM and 551 sites/cell, and 1.10 nM and 560 sites/cell with 20 nM 19-OH-AD. A high concentration of 19-OH-AD slightly displaced 0.2 or 5 nM of [H-3]aldosterone bound to MNL.
In both tissues, there was no obvious specific binding of [H-3]19-OH-AD within the range of 1-60 nM.
The above results suggest that the amplifying effect of 19-OH-AD on aldosterone mineralocorticoid action may not occur at the binding site of aldosterone to type I receptor, and that 19-OH-AD itself may not have any direct or indirect mineralocorticoid actions on the steroid receptor-mediated process in the rat kidney and human MNL.
- リンク情報
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- DOI
- https://doi.org/10.1016/0960-0760(91)90104-D
- CiNii Articles
- http://ci.nii.ac.jp/naid/80005840279
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/2009224
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:A1991FG55800007&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1016/0960-0760(91)90104-D
- ISSN : 0960-0760
- CiNii Articles ID : 80005840279
- PubMed ID : 2009224
- Web of Science ID : WOS:A1991FG55800007