ONTOGENY OF LACTOFERRIN IN THE DEVELOPING MOUSE UTERUS - A MARKER OF EARLY HORMONE RESPONSE

Lactoferrin (LF) was mapped during organogenesis of the murine reprodu ctive tract, starting on fetal Day 12, as a marker of estrogen respons iveness. To induce LF expression, pregnant outbred CD-1 mice were inje cted s.c. with diethylstilbestrol (DES; 100 mu g/kg maternal body weig ht), and fetal genital tract tissues were removed; neonatal and immatu re mice received s.c. injections of DES (2 mu g/pup per day). Corn oil -treated and untreated mice at corresponding ages provided the control s. Immunocytochemical techniques using a polyclonal antibody showed no detectable LF in control genital tract tissues until late gestation. However, after DES treatment, LF was localized in uterine epithelial c ells as early as fetal Day 14; the intensity of LF staining increased with age and number of DES treatments. Control uterine tissues respond ed to the rise of circulating estrogens at parturition (fetal Day 19) by producing LF, although the magnitude of response was lower than tha t of DES-treated tissues. Uterine tissue homogenates from control and DES mice were analyzed by SDS-PAGE and Western blots, verifying the pr otein to be LF. Isolation of mRNA and Northern blot analysis further s howed that LF mRNA was present in the developing Mullerian duct and th at DES stimulated early induction of the LF gene. The early appearance of LF suggests that it may play an important role in the hormonal reg ulation of growth and differentiation of developing uterine tissues.