Progesterone and dexamethasone inhibition of uterine epithelial cell proliferation: Studies with antiprogesterone compounds in the neonatal mouse

Robert M. Bigsby, Peter C.M. Young

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Progestins and glucocorticoids inhibit uterine epithelial cell proliferation. Earlier studies showed that in the neonatal mouse, dexamethasone (Dex) was at least 100-fold more potent than progesterone (P) as an inhibitor of epithelial DNA synthesis. Using steroid autoradiography, we now show that the uterine cells of the neonatal mouse have receptors for both progestins (PR) and glucocorticoids (GR). Since it is known that P can interact with the GR it is possible that even a weak interaction might mediate the inhibitory effects of large doses of P. Therefore, we examined the receptor pathway specificity of the P response in neonatal mice using antiP steroids with reported strong antiglucocorticoid activity, RU486, or weak antiglucocorticoid activity, ZK98.734 (ZK734). Both RU486 and ZK734 exhibited strong binding activity in a PR assay performed on cytosolic preparations from adult mouse uteri. For murine thymic GR, the relative binding activity of RU486 was 12-fold that of ZK734. The high PR binding activity was reflected by the in vivo dose-response of the antagonists administered in conjunction with P; either antagonist completely blocked the inhibitory effect of P on uterine epithelial DNA synthesis when it was administered at one-tenth the dose of P. On the other hand, blockade of the inhibitory effect of Dex only occurred when the dose of antagonist was 10-fold the dosage of Dex. There were no significant differences between the two antagonists in blocking the effects of either P or Dex. These results indicate that progestins and glucocorticoids act through their own receptor systems to inhibit DNA synthesis in the uterine epithelium of the neonatal mouse. However, becuase of the considerable antiglucocorticoid activity of ZK734, a potential role for the interaction between P and the GR cannot be ruled out by these experiments.

Original languageEnglish (US)
Pages (from-to)253-257
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume46
Issue number2
DOIs
StatePublished - Aug 1993

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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