Role of Cyclin-Dependent Kinase Inhibitors in Estrogen Regulation of Adipogenesis
Naaz, Afia
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/87130
Description
Title
Role of Cyclin-Dependent Kinase Inhibitors in Estrogen Regulation of Adipogenesis
Author(s)
Naaz, Afia
Issue Date
2005
Doctoral Committee Chair(s)
Cooke, Paul S.
Department of Study
Veterinary Clinical Medicine
Discipline
Veterinary Clinical Medicine
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Nutrition
Language
eng
Abstract
Adipose tissue is responsive to steroid hormones like estrogen. Loss of estrogen receptor a (ERalpha) caused a 100% increase in adipose tissue, indicating the importance of ERalpha signaling. ERalpha knockout mice (alphaERKO) mice have intact ERbeta signaling. Removal of ERbeta/estrogen signaling in the absence of ERalpha/E2 signaling decreased adipose tissue indicating that ERalpha and ERbeta might have an opposite effect in adipose tissue. The obese phenotype in alphaERKO mice is due to both hypertrophy and hyperplasia of adipocytes. Since estrogen has an effect on the levels of cell cycle inhibitors like p27 Kip1 (p27) and p21 Cip1 (p21) in breast cancer cell lines, estrogen might have an effect on the number of adipocytes by its effect on these proteins. Lack of p27 and p21 caused obesity due to hyperplasia in mice, which led to metabolic disorders. This increase in obesity was due to increase in transcriptional factors like C/EBPbeta, C/EBPalpha, PPARgamma and Glut4. Wild-type (WT) mouse embryonic fibroblast (MEFs) had increased mitotic clonal expansion (MCE) due to lack of estrogen but this was not seen in p27KO MEFs, that showed that the effects due to these two pathways were not additive and a possibility that they might be acting through the same pathway. ERalpha signaling was increased in p27KO MEFs during adipogenesis indicating that the pathways of ERalpha/E2 signaling and p27 activity during adipogenesis might be connected. In conclusion these studies have shown that though ERalpha is the major receptor involved in ER/E2 signaling in adipose tissue, ERbeta might also have a role which is opposite of ERalpha. The hyperplasia in adipocytes caused by lack of estrogen might be due to its effect on the signaling pathways of cell cycle inhibitors like p27. Increase in the number of adult adipocytes due to the activities of these pathways would ultimately lead to obesity and metabolic disorders associated with obesity in the animal.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
