Inhibitory effect of all-trans retinoic acid on androgen-induced growth of mouse seminal vesicles in vivo and its mechanism.
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.
Sato
Hideki
H
Department of Urology, Ehime University, School of Medicine, Ehime, Japan.
Tanji
Nozomu
N
Tsuji
Motomu
M
Terada
Nobuyuki
N
Yamasaki
Kenshi
K
Wang
Jianbo
J
Sakayama
Kenshi
K
Yokoyama
Masayoshi
M
D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009919:Orchiectomy; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000032:analysis; D000072482:Retinoic Acid Receptor alpha; D012669:Seminal Vesicles / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D043343:Testosterone Propionate; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*
C000607072:Rara protein, mouse; D011944:Receptors, Androgen; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D043343:Testosterone Propionate