Identification of steroid sulfate transport processes in the human mammary gland

Pizzagalli, F. and Varga, Z. and Huber, R. D. and Folkers, G. and Meier, P. J. and St-Pierre, M. V.. (2003) Identification of steroid sulfate transport processes in the human mammary gland. Journal of clinical endocrinology and metabolism, Vol. 88, H. 8. pp. 3902-3912.

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Official URL: http://edoc.unibas.ch/dok/A5261614

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Circulating hormones and local biotransformation of steroid precursors are both sources of estrogen in human mammary tissue. Estrone-3-sulfate (E(1)S) is an important estrogenic form in premenopausal women, and dehydroepiandrosterone sulfate (DHEAS) constitutes a major adrenal precursor. Membrane transport systems that govern delivery of these anionic steroid conjugates to the mammary gland were investigated. RNA was screened by RT-PCR and Northern blotting for expression of organic anion transporting polypeptide (OATP) (solute carrier family 21A) and organic anion transporter (OAT) (solute carrier family 22A) gene families. OATP-B (SLC21A9) was the major carrier expressed; OATP-D (SLC21A11) and OATP-E (SLC21A12) were less abundant. In normal sections, OATP-B immunolocalized to the myoepithelium that surrounds the ductal epithelial cells. In invasive carcinoma, ductal epithelial cells were positive. OATP-B was characterized in stable transfected Chinese hamster ovary cells. E(1)S affinity constant (K(m)) [K(m) = 5 micro mol/liter, maximum velocity (V(max)) V(max) = 777 pmol/mg.min] and DHEAS (K(m) = 9 micro mol/liter, V(max) = 85 pmol/mg.min) were substrates. The prostaglandins (PG) A(1) and PGA(2) stimulated uptake of E(1)S and DHEAS by increasing V(max) 2-fold but not changing K(m). The effect of PGA was selectively blocked by the lipophilic thiol reagent N-ethylmaleimide but not by the hydrophilic acetamido-4'(iodoacetyl)aminostilbene-2,2'-disulfonic acid, suggesting an interaction between the electrophilic cyclopentenone ring and specific cysteine residues of OATP-B.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Dec 2015 10:44
Deposited On:22 Mar 2012 13:41

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