Characteristics of a membrane-associated antilactogen binding site for tamoxifen

Mol Cell Endocrinol. 1993 Dec;98(1):1-8. doi: 10.1016/0303-7207(93)90229-d.


The antilactogen binding site (ALBS) is a membrane associated protein to which tamoxifen (TAM) and related non-steroidal antiestrogens, but not estrogen, bind. It is through this site that TAM inhibits lactogen binding to the prolactin (Prl) receptor and subsequent Prl induced growth and differentiation in target tissues. Binding of lactogens to the Prl receptor is inhibited by TAM or 4-hydroxy-TAM at 4 degrees C as well as room temperature, thus suggesting that the ALBS is not an enzyme. TAM acts by inhibiting the binding of lactogens to the receptor rather than promoting dissociation of the hormone-receptor complex. Lactogens bind to mammary gland membranes with an Kd of 4.3-8.2 x 10(-10) M. In the presence of 10(-7) M TAM the affinity decreased to a Kd of 0.8-1.6 x 10(-9) M. Binding of 3H-TAM to mammary gland membranes was effectively inhibited by an anti-Prl receptor antibody, thus suggesting a close relationship between the Prl receptor and the ALBS. Separate affinity purification of the ALBS and the Prl receptor resulted in peak fractions demonstrating specific binding activity for both TAM and lactogenic hormones. Re-isolation of the affinity purified Prl receptor on a TAM-Sepharose affinity resin again resulted in co-elution of both binding activities. The isolates from both affinity resins contained primarily a single band with an apparent molecular mass of 90 kDa. This band was precipitated with the anti-Prl receptor antibody and specifically bound the affinity label ring-3H-TAM aziridine.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Cholic Acids / pharmacology
  • Chromatography, Affinity
  • Female
  • Kinetics
  • Lactation
  • Liver / metabolism
  • Mammary Glands, Animal / metabolism
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Prolactin / metabolism
  • Protein Binding
  • Receptors, Drug / isolation & purification
  • Receptors, Drug / metabolism
  • Receptors, Prolactin / isolation & purification
  • Receptors, Prolactin / metabolism
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / metabolism*


  • Cholic Acids
  • Membrane Proteins
  • Receptors, Drug
  • Receptors, Prolactin
  • Tamoxifen
  • tamoxifen aziridine
  • Prolactin
  • 3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate