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Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones
Breast cancer resistance protein (BCRP) is known for its protective function against the toxic effects of exogenous compounds. In addition to this, a role in the transport of endogenous compounds has been described. Since BCRP in the plasma membrane was shown to be regulated by sex steroids, we inve...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414710/ https://www.ncbi.nlm.nih.gov/pubmed/22581381 http://dx.doi.org/10.1007/s00441-012-1417-5 |
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author | Dankers, Anita C. A. Sweep, Fred C. G. J. Pertijs, Jeanne C. L. M. Verweij, Vivienne van den Heuvel, Jeroen J. M. W. Koenderink, Jan B. Russel, Frans G. M. Masereeuw, Rosalinde |
author_facet | Dankers, Anita C. A. Sweep, Fred C. G. J. Pertijs, Jeanne C. L. M. Verweij, Vivienne van den Heuvel, Jeroen J. M. W. Koenderink, Jan B. Russel, Frans G. M. Masereeuw, Rosalinde |
author_sort | Dankers, Anita C. A. |
collection | PubMed |
description | Breast cancer resistance protein (BCRP) is known for its protective function against the toxic effects of exogenous compounds. In addition to this, a role in the transport of endogenous compounds has been described. Since BCRP in the plasma membrane was shown to be regulated by sex steroids, we investigated the presence and possible role of BCRP in steroid hormone-producing organs. Therefore, the presence and localization of Bcrp was investigated in endocrine organs of wild-type mice. Furthermore, the interaction of various steroid hormones with human BCRP activity was studied. Quantitative PCR revealed Bcrp mRNA in the pituitary and adrenal glands, pancreas, ovary, testis and adipose tissue. Immunohistochemistry revealed the presence of Bcrp in the cortex of the adrenal gland and in plasma membranes of adipocytes. In the pituitary gland, pancreas, ovary and testis, Bcrp was mainly located in the capillaries. The interaction between BCRP and 12 steroid hormones was studied using membrane vesicles of HEK293-BCRP cells. Estradiol, testosterone, progesterone and androstenedione inhibited BCRP-mediated uptake of (3)H-estrone sulphate (E(1)S) most potently, with calculated inhibitory constant (Ki) values of 5.0 ± 0.2, 36 ± 14, 14.7 ± 1.3 and 217 ± 13 μM, respectively. BCRP function was attenuated non-competitively, which implies an allosteric inhibition of BCRP-mediated E(1)S transport by these steroids. In conclusion, localization of Bcrp in endocrine organs together with the efficient allosteric inhibition of the efflux pump by steroid hormones are suggestive for a role for BCRP in steroid hormone regulation. |
format | Online Article Text |
id | pubmed-3414710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-34147102012-08-16 Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones Dankers, Anita C. A. Sweep, Fred C. G. J. Pertijs, Jeanne C. L. M. Verweij, Vivienne van den Heuvel, Jeroen J. M. W. Koenderink, Jan B. Russel, Frans G. M. Masereeuw, Rosalinde Cell Tissue Res Regular Article Breast cancer resistance protein (BCRP) is known for its protective function against the toxic effects of exogenous compounds. In addition to this, a role in the transport of endogenous compounds has been described. Since BCRP in the plasma membrane was shown to be regulated by sex steroids, we investigated the presence and possible role of BCRP in steroid hormone-producing organs. Therefore, the presence and localization of Bcrp was investigated in endocrine organs of wild-type mice. Furthermore, the interaction of various steroid hormones with human BCRP activity was studied. Quantitative PCR revealed Bcrp mRNA in the pituitary and adrenal glands, pancreas, ovary, testis and adipose tissue. Immunohistochemistry revealed the presence of Bcrp in the cortex of the adrenal gland and in plasma membranes of adipocytes. In the pituitary gland, pancreas, ovary and testis, Bcrp was mainly located in the capillaries. The interaction between BCRP and 12 steroid hormones was studied using membrane vesicles of HEK293-BCRP cells. Estradiol, testosterone, progesterone and androstenedione inhibited BCRP-mediated uptake of (3)H-estrone sulphate (E(1)S) most potently, with calculated inhibitory constant (Ki) values of 5.0 ± 0.2, 36 ± 14, 14.7 ± 1.3 and 217 ± 13 μM, respectively. BCRP function was attenuated non-competitively, which implies an allosteric inhibition of BCRP-mediated E(1)S transport by these steroids. In conclusion, localization of Bcrp in endocrine organs together with the efficient allosteric inhibition of the efflux pump by steroid hormones are suggestive for a role for BCRP in steroid hormone regulation. Springer-Verlag 2012-05-13 2012 /pmc/articles/PMC3414710/ /pubmed/22581381 http://dx.doi.org/10.1007/s00441-012-1417-5 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License, which permits any use, distribution and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Regular Article Dankers, Anita C. A. Sweep, Fred C. G. J. Pertijs, Jeanne C. L. M. Verweij, Vivienne van den Heuvel, Jeroen J. M. W. Koenderink, Jan B. Russel, Frans G. M. Masereeuw, Rosalinde Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
title | Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
title_full | Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
title_fullStr | Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
title_full_unstemmed | Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
title_short | Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
title_sort | localization of breast cancer resistance protein (bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414710/ https://www.ncbi.nlm.nih.gov/pubmed/22581381 http://dx.doi.org/10.1007/s00441-012-1417-5 |
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