Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle.
OBJECTIVE
During each oestrous cycle, the mammary gland is subject to changes in ovarian hormone levels. It responds with limited proliferation, differentiation and regression. To understand the processes resulting in these changes, particularly the regulation of cell death, we examined protein levels in mammary epithelium during the oestrous cycle of the Sprague-Dawley rat.


METHODS
Studies of serum hormone levels, vaginal smears, uterine weight and morphology, mammary gland morphology, proliferation and apoptotic indices, and protein levels during the stages of the Sprague-Dawley rat oestrous cycle were used to examine the response of mammary epithelium to the oestrous cycle.


RESULTS
Proliferation of mammary epithelium was greater in diestrus and proestrus, while apoptosis was increased in metestrus and diestrus. Growth factor-, hormone- and anchorage-mediated cell survival signalling, indicated by activation of Stat5A, FAK and Akt 1 and expression of anti-apoptotic Bcl-2 family members, was greater in proestrus and reduced in metestrus. In contrast, the levels of pro-apoptotic Bcl-2 family members and proteins associated with apoptosis in mammary epithelium (TGFbeta3, pStat3) were increased during metestrus and diestrus.


CONCLUSIONS
Decreases in growth factor, hormone and cell attachment survival signals corresponded with increased apoptosis during the second half of the oestrous cycle. The protein levels detected during oestrus suggest parallels to apoptosis in mammary involution.
Strange
R
R
Division of Medical Oncology, University of Colorado Health Sciences Center, Denver, CO 80214, USA. robert.strange@uchsc.edu
Westerlind
K C
KC
Ziemiecki
A
A
Andres
A-C
AC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001798:Blood Proteins / Q000032:analysis; D002455:Cell Division / Q000502:physiology*; D002470:Cell Survival; D004031:Diestrus / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000502:physiology*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000502:physiology*; D011359:Proestrus / Q000502:physiology; D011374:Progesterone / Q000097:blood; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001798:Blood Proteins; D036341:Intercellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011374:Progesterone; D004958:Estradiol; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D051057:Proto-Oncogene Proteins c-akt