Received for publication June 30, 2004.
Revised October 14, 2004.
Accepted for publication October 15, 2004.

Xenobiotic and Endobiotic Transporter mRNA Expression in the Blood-Testis Barrier

Abstract

A major function of xenobiotic and endobiotic transporters is to move a wide range of organic substances across cell membranes. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. The aim of this study was to quantitatively determine the constitutive expression of various transporters in isolated Sertoli cells from adult Sprague-Dawley rats. The following mRNA levels were measured in isolated Sertoli cells by the branched DNA signal amplification method: Mdr1a, 1b and 2; Mrp1, 2, 3, 4, 5, 6, 7, and 8; Ntcp, Bsep, Ibat, AbcG5 and AbcG8; Oatp1, 2, 3, 4, 5, 9, 12, Pgt,Tst1, and Tst2; Oat1, 2, 3, and K; Oct1, 2, 3, N1 and N2; Dmt1, Menke's, Wilson's, Znt1; Ent1, 2, Cnt1, 2, Pept1, and 2. Levels were also determined in whole testis, liver, kidney, and ileum to provide a reference for determining relative expression levels. Mrp8, Tst1 and 2, and Ent1 and 2 were expressed in Sertoli cells at higher levels than in liver, kidney or ileum, whereas Mrp1, 5 and 7, Mdr2, Oatp3, Oat2, OctN2, Dmt1, Menke's, Wilson's, and Znt1 were all significantly expressed in Sertoli cells, but Sertoli cell expression was not the tissue of highest expression. The remaining transporters were expressed at low levels in isolated Sertoli cells. Additionally, expression levels of Mrp1, Mrp7, Mrp8, Tst1, Tst2, OctN2, Wilson's, Znt1, Ent1 and Ent2 were greater in isolated Sertoli cells than in whole testis. Constitutive expression of transporters in Sertoli cells may provide an insight into the range of xenobiotics that can potentially be transported by Sertoli cells and thereby provide a mechanistic understanding of blood-testis barrier function.

Key words: antivirals, cellular transport, drug distribution, drug transport, metal ion transporters, reproductive toxicology, transporters

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