Inhibitory effect of all-trans retinoic acid on androgen-induced growth of mouse seminal vesicles in vivo and its mechanism

Hum Exp Toxicol. 2005 Sep;24(9):467-74. doi: 10.1191/0960327105ht555oa.

Abstract

We examined the effect of all-trans retinoic acid (ATRA) on the androgen-induced growth of mouse seminal vesicles (SVs) in vivo and its mechanisms. Testosterone propionate (TP) alone or with ATRA was injected daily into adult castrated BALB/c mice. Injections of ATRA significantly inhibited the TP-induced growth of SVs in terms of wet weight and DNA synthesis by a pair of SVs evaluated by [3H]thymidine uptake. The bromodeoxyuridine labelling index showed that ATRA inhibited the proliferation of both epithelial and stromal cells. Immunoreactivity for retinoic acid receptor-alpha was found in the basal epithelial cells. Injections of ATRA affected neither 5alpha-reductase activity nor the expression of mRNAs for TGF-beta1, 2 and 3 and TGF-beta receptor 1 and 2 in the SVs. However, androgen receptor (AR) binding assays and Western blotting revealed a decrease in AR without a change in ligand-binding affinity. The present study showed that retinoid inhibited the androgen-induced growth of mouse SVs in vivo, and suggests that a decrease in AR is one of its mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Proliferation / drug effects
  • Epithelial Cells / chemistry
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Orchiectomy
  • Receptors, Androgen / drug effects*
  • Receptors, Androgen / metabolism
  • Receptors, Retinoic Acid / analysis
  • Retinoic Acid Receptor alpha
  • Seminal Vesicles / drug effects*
  • Seminal Vesicles / growth & development
  • Seminal Vesicles / metabolism
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Testosterone Propionate
  • Time Factors
  • Tretinoin / administration & dosage
  • Tretinoin / pharmacology*

Substances

  • Rara protein, mouse
  • Receptors, Androgen
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Tretinoin
  • Testosterone Propionate