Immunohistochemical Study of Estrogen-induced Lactoferrin-like Protein in the Mouse Uterus: Localization in the Nucleolus and Secretory Pathway

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Lactoferrin (LF) is known as an estrogen-inducible protein in the murine uterus. This study, employing immunoelectron microscopy with the pre-embedding methods, was carried out to elucidate temporal LF induction, the process of the induction and intracellular localization after 17βestradiol (E2) stimulation in the enodometrial epithelium of ovariectomized adult mice. By single i. p. injection of E2 (20μg/kg b. w.), LF was rapidly induced, even after 1 hr, and was exclusively localized in the nucleoli of surface and glandular epithelium. At 7 hr after E2 injection, strong immunostaining was recognized in the amorphous cytoplasm and in nucleoli, especially in the dense fibrillar component of the epithelium. From 13 hr to 23 hr after E2 administration, strong reaction was observed in the secretory pathway, i. e., cisternae of endoplasmic reticulum and the Golgi apparatus, and in vesicles and vacuoles in the apical cytoplasm, in addition to the nucleolar staining. LF-immunoreaction was also detected in the nucleoli and cytoplasm of stromal and muscle cells; it was demonstrated in the epithelium at the earliest period, subsequently in the stromal cells (7 hr), and finally in the muscle cells (13 hr). After three days of consecutive E2 stimulation, many secretory granules in the apical cytoplasm and apical cell membrane showed intense LF immunoreaction. The present study suggests that LF in the nucleolus plays an important role in activation of ribosomal biogenesis preceding the cell differentiation and proliferation in the mouse uterus.