bcrp - publications

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1. Cell Tissue Res. 2012 May 13. [Epub ahead of print]

Localization of breast cancer resistance protein (Bcrp) in endocrine organs and
inhibition of its transport activity by steroid hormones.

Dankers AC, Sweep FC, Pertijs JC, Verweij V, van den Heuvel JJ, Koenderink JB,
Russel FG, Masereeuw R.

Department of Pharmacology and Toxicology (149), Nijmegen Centre for Molecular
Life Sciences / Radboud University Nijmegen Medical Centre, P. O. Box 9101, 6500
HB, Nijmegen, The Netherlands.

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

PMID: 22581381 [PubMed - as supplied by publisher]