Eckhardt K, Schmitt G
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Toxicol Lett. 1994 Feb 15;70(3):299-308. doi: 10.1016/0378-4274(94)90124-4.
The role of retinoic acid receptors (RAR) in retinoid-induced teratogenesis is mainly unknown. The aim of the present studies was to demonstrate the effect of a RAR alpha antagonist on retinoid-induced teratogenic effects in vitro and in vivo. In micromass cultures of rat limb bud cells a RAR alpha antagonist was able to counteract differentiation inhibiting effects of a RAR alpha agonist. In mouse studies, the selective RAR alpha antagonist reduced frequency and/or severity of major malformations. Our observations indicate the potentiality of selective RAR agonists and antagonists in dissecting the function of nuclear receptors and in particular cases of retinoid teratogenesis, to assign to the different receptors a primary role in determining one or another of the multiple malformations.
视黄酸受体（RAR）在类视黄醇诱导的致畸作用中的角色主要尚不清楚。本研究的目的是证明RARα拮抗剂对体外和体内类视黄醇诱导的致畸作用的影响。在大鼠肢芽细胞的微团培养中，RARα拮抗剂能够抵消RARα激动剂的分化抑制作用。在小鼠研究中，选择性RARα拮抗剂降低了主要畸形的发生率和/或严重程度。我们的观察结果表明，选择性RAR激动剂和拮抗剂在剖析核受体功能以及在类视黄醇致畸的特定情况下，将多种畸形中的一种或另一种的主要作用分配给不同受体方面具有潜力。
