The in vitro metabolism of 13-cis-retinoic acid in a model sebaceous structure, the rat preputial gland.

ABSTRACT

In order to study the metabolism of 13-cis-retinoic acid (13-cis-RA) in animal sebaceous glands and analogues, preputial glands from normal and vitamin A-deficient male rats were incubated with [3H]13-cis-RA for up to 24 h; vitamin A-normal hamster costovertebral glands (flank organs) were incubated for 24 h as well. High-performance liquid chromatography was used to identify the metabolites. [3H]13-cis-RA was rapidly converted to a less polar compound, [3H]all-trans-retinoic acid, by the preputial glands from both normal and deficient rats. In normal preputial glands, the level of [3H]all-trans-RA decreases and two more polar compounds, metabolite I and [3H]4-keto-13-cis-RA appear. In contrast, [3H]all-trans-RA is not metabolized further by the preputial glands from deficient rats, while [3H]13-cis-RA in the hamster costovertebral glands remains intact for up to 24 h. The major metabolite of [3H]13-cis-RA in rat preputial glands is [3H]4-keto-13-cis-RA. Initially, [3H]13-cis-RA is converted to [3H]all-trans-RA. In vitamin A-deficient rats the preputial glands fail to further metabolize [3H]13-cis-RA to the more polar [3H]13-cis-RA derivatives. This may be due to the reduced level of P-450 enzyme in vitamin A-deficient rat preputial glands.