Pharmacological activity of retinoic acid receptor alpha-selective antagonists in vitro and in vivo.

ABSTRACT: Oral administration of a retinoic acid receptor (RAR) pan-antagonist reversibly inhibits spermatogenesis. Given the importance of RARα in regulating spermatogenesis, we identified two RARα-selective antagonists by transactivation and transactivation competition assays and asked whether they effectively inhibit spermatogenesis. Although these two antagonists were potent in vitro, they displayed poor in vivo activity in mice when administered orally. Testicular weights were normal and morphological analysis revealed normal spermatid alignment and sperm release. In vitro drug property analyses were performed with one of these antagonists and compared with the pan-antagonist. We showed that the discrepancies may be explained by several factors, including high plasma protei

SUBMITTER: Chung SS 

PROVIDER: S-EPMC3770188 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature