VAGINAL KERATINIZATION DURING THE ESTROUS-CYCLE IN RATS - A MODEL FOREVALUATING RETINOID ACTIVITY

A model is described for evaluating the activity of a retinoid based o n its effect on the keratinization of the vaginal epithelium that occu rs on estrus (day 4) of a 4-day cycle in female rats, This keratinizat ion process is dependent on the endogenous estradiol (E(2)) secreted b etween the evening of diestrus 2 (day 2) and that of proestrus (day 3) , Various doses of all-trans-retinoic acid (tRA) were injected at diff erent time points during the estrous cycle and the vaginal keratinizat ion was assessed by microscope examination of unstained native or Papa nicolaou-stained smear preparations, Additionally, the preovulatory E( 2) secretion was measured and ovaries were histologically examined, A single injection of 10 mg/kg tRA either on diestrus 2 (evening) or on proestrus (early morning) was able to induce a complete inhibition of the vaginal keratinization in more than 80% of the cases, This can be considered as a direct effect on the vaginal epithelial differentiatio n since neither the E(2) secretion nor the ovulatory process were affe cted, The inhibition of vaginal keratinization can be used as a rapid and convenient in vivo model for screening retinoid candidates with an tikeratinizing activity.