Vaginal permeability and enzymatic activity studies in normal and ovariectomized rabbits

Abstract

Purpose: This study was initiated to develop an animal model, using ovariectomized rabbits, for the post-menopausal human, based on in vitro vaginal tissue permeability and aminopeptidase activity.

Methods: An enkephalin derivative [D-ala(2),N-methyl-phe(4)-glycol(5)][tyrosyl-3,5-(3)H] enkephalin {[(3)H] RX 783006), which has relative enzymatic stability to aminopeptidases and dipeptidyl peptidase, was used as a model peptide drug for permeability experiments. Aminopeptidase activity in vaginal homogenates, as well as in tissue pieces, was determined using 4-methoxy-2-naphthylamides of leucine, alanine, arginine, and glutamic acid as specific substrates. In addition, histological examination of normal and ovariectomized vaginal tissues was performed.

Results: Vaginal permeability of the drug was significantly increased in the ovariectomized compared to the intact animal. The full vaginal tissue became thinner and mucosal epithelial thickness was reduced about two-fold after ovariectomization and vaginal cells from the castrated rabbit were typically immature. Aminopeptidase activity, leucine aminopeptidase, aminopeptidase B and A, was the same in vaginal tissue homogenates and whole-tissue specimens in both normal and ovariectomized rabbits whereas the activity of aminopeptidase N was significantly decreased in ovariectomized as compared to normal rabbits.

Conclusions: Based on the present data, the ovariectomized rabbit may be useful as an animal model for postmenopausal vaginal studies.