Identification of steroid sulfate transport processes in the human mammary gland

J Clin Endocrinol Metab. 2003 Aug;88(8):3902-12. doi: 10.1210/jc.2003-030174.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Biological Transport, Active
  • Blotting, Northern
  • Breast / metabolism*
  • Breast Neoplasms / metabolism
  • CHO Cells
  • Cricetinae
  • Dehydroepiandrosterone Sulfate / metabolism
  • Epithelium / metabolism
  • Estrone / analogs & derivatives*
  • Estrone / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroids / metabolism*
  • Sulfates / metabolism
  • Transfection


  • Organic Anion Transporters
  • Steroids
  • Sulfates
  • Estrone
  • Dehydroepiandrosterone Sulfate
  • estrone sulfate