Figure 1.

Uninterrupted drug administration induces discontinuous reporter accumulation. Profile of photon emission in 21 d in skeletal (A), hepatic (B), and genital (C) areas of single, representative, OVX ERE-Luc mice after treatment with vehicle (veh), E2, or LAS. Drugs were administered via a dorsal implant of a continuous-release pellet delivering the compounds at a fixed concentration. Photon emission in discrete body regions was segmented in a Matlab environment using an algorithm previously described (25) and defined as the number of counts per second per centimeter square (cts/cm²s) corrected for instrument efficiency. In a parallel experiment, photon emission was measured daily in individual animals treated with vehicle (veh) or E2; groups of six mice were euthanized at the high (H) or low (L) photon emission (D and E), blood was collected, and uterus and liver tissues were dissected. F, Luciferase enzymatic activity in liver tissue extracts. G, E2 content was measured in samples of plasma pooled from two mice using gas chromatography mass spectrometry (see Materials and Methods). The analysis was done in duplicate on a total of three samples for each experimental condition. H, Weight of uterus frozen tissue. Bars represent mean ± sem (n = 6). *, P = 0.043 (D); *, P = 0.043 (E); **, P = 0.002 (F); **, P = 0.003 (H) (ANOVA followed by Bonferroni). I, ERα protein content as measured by Western blot in liver tissue extracts (n = 6).