Evidence for two progesterone receptor binding sites in murine mammary carcinomas

J Steroid Biochem Mol Biol. 2003 Jan;84(1):9-14. doi: 10.1016/s0960-0760(02)00267-4.

Abstract

We have evaluated the progesterone receptor (PR) binding patterns in progestin-dependent and -independent murine mammary carcinomas; all variants regress completely after antiprogestin treatment. These studies revealed the presence of a high affinity, low capacity-binding site (K(d): 43 +/- 9 pM; Q=9 +/- 3 fmol/mg protein) and of the classical lower affinity, high capacity-binding site (K(d): 9.2 +/- 4.2 nM; Q=376 +/- 64 fmol/mg protein). These sites could also be detected in uterus. Antiprogestins were able to bind to both sites. In vitro, medroxyprogesterone acetate (MPA) was stimulatory along a biphasic curve with two slopes, one at very low concentrations (EC(50): 1.5 +/- 0.7 fM) and the other at values compatible with the described K(d) for the PR (EC(50): 0.33 +/- 0.3 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Carcinoma / metabolism*
  • Cell Division
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Female
  • Fibroblasts / cytology
  • Kinetics
  • Mammary Neoplasms, Animal / metabolism*
  • Medroxyprogesterone Acetate / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Progesterone Congeners / pharmacology
  • Progestins / pharmacology
  • Protein Binding
  • Receptors, Progesterone / chemistry*
  • Receptors, Progesterone / metabolism*
  • Time Factors
  • Uterus / metabolism

Substances

  • Progesterone Congeners
  • Progestins
  • Receptors, Progesterone
  • Medroxyprogesterone Acetate