EFFECT OF 5-AMINOLEVULINIC ACID DOSE AND ESTROGEN ON PROTOPORPHYRIN-IX CONCENTRATIONS IN THE RAT UTERUS

OBJECTIVES: To determine the in vivo dose-response relation between ad ministered 5-aminolevulinic acid (ALA) and the concentration of protop orphyrin, IX (PpIX) produced in rat uterine tissue, to determine the e ffect of estrogen on ALA-induced PpIX production in the rat endometriu m and myometrium, and to determine the selectivity of ALA-induced PpIX production in uterine tissue. METHODS: Ovary-intact female rats (n = 53) received a subcutaneous estradiol-17 beta (E2) implant. Three days later, ALA dissolved in saline (0, 1, 2.5, 10, 25, or 50 mg/100 mu L) was injected into one uterine horn. Three hours after ALA administrat ion, the uterus was removed and the endometrium was scraped from the m yometritirn. In a second study, rats (n = 35) were ovariectomized and 8 days later given either an E2 or sham implant. After 3 days of hormo nal or sham priming, ALA (10 or 25 mg) was injected into the uterine h orn 3 hours before hysterectomy. In both studies, PpIX was extracted i n a method/percholic acid (1:1) solution and quantified spectrofluorom etrically. RESULTS: Five-aminolevulinic acid increased PpIX concentrat ions in the endometrium and myometrium in a dose-dependent fashion. Tw enty-five milligrams of ALA produced maximum PpIX concentrations in bo th the endometrium and myometrium. In the second study, sham-implanted ovariectomized rats had endometrial PpIX concentrations approximately two times higher than those in the estrogen-primed rats after doses o f either 10 or 25 mg ALA. In the third study, the endomctrium had two to three times higher PpIX concentrations than the myometrium at 1, 10 , 25, and 50 mg of ALA. CONCLUSIONS: An in vivo dose-response relation was demonstrated between ALA and uterine production of PpIX, with max imum PpIX concentrations occurring after 25 mg of intrauterine ALA. Be cause estrogen was not required to convert ALA to PpIX, complete endom etrial ablation may best be achieved with an unstimulated endometrium. Copyright (C) 1997 by the Society for Gynecologic Investigation.