Address for correspondence: Marit Nilsen-Hamilton, Department of Biochemistry, Biophysics, and Molecular Biology, 3206 Molecular Biology Building, Iowa State University, Ames, IA 50011. Voice: 515-294-9996; fax: 515-294-0453.
marit{at}iastate.edu
Ann. N.Y. Acad. Sci. 995: 94-108 (2003).
After their roles in reproduction are completed, the mass of
the uterus and the mammary gland decrease rapidly by the process
of involution that involves an ordered series of events including
apoptosis, neutrophil entry, the release of degradative enzymes,
and phagocytosis of cellular debris. The acute phase proteins
are produced by the liver and other tissues in response to inflammation
or a toxic challenge. Uterocalin (SIP24/24p3) is one of these
proteins. During involution, the mammary gland and uterus express
high levels of uterocalin that reach an average of 0.2-0.5%
of the total extractable protein at its peak. Uterocalin and
its orthologues have been demonstrated
in vitro to (1) bind
certain fatty acids and (2) specifically induce apoptosis in
neutrophils and other leukocytes. The period of uterocalin expression
during involution is consistent with the hypothesis that one
of its physiological roles is to induce apoptosis of invading
neutrophils and delay the entry of neutrophils into the tissue
until the second phase of involution. Interestingly, it has
been shown that uterocalin expression remains higher in primiparous
gland than in virgin glands after the pregnant glands have completely
involuted. This observation and the known protective effect
of early pregnancy on later development of breast cancer suggest
that the ability of uterocalin to induce apoptosis in neutrophils
might also decrease oxidative and carcinogenic activity in the
gland and result in a lower mutation rate and thus a lower probability
of cancer in the primiparous gland.
