Skip to main content
ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #166329
Title: SUB-FERTILITY, UTERINE HYPOPLASIA, AND PARTIAL PROGESTERONE RESISTANCE IN MICE LACKING THE KRUPPEL-LIKE FACTOR 9/BASIC TRANSCRIPTION ELEMENT BINDING PROTEIN-1 (BTEB1) GENE

Author
item SIMMEN, R - ACNC
item EASON, RENEA - ACNC
item MCQUOWN, JENNELLE - UNIV OF FLORIDA
item LINZ, AMANDA - ACNC
item KANG, TEE-JUNG - UNIV OF FLORIDA
item CHATMAN, LEON - ACNC
item TILL, SHARON - ACNC
item KURIYAMA, YOSHIAKI - UNIV TSUKUBA, JAPAN
item SIMMEN, FRANK - ACNC
item OH, PAUL - UNIV OF FLORIDA

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2004
Publication Date: 7/9/2004
Citation: Simmen, R.C., Eason, R.R., Mcquown, J.R., Linz, A.L., Kang, T., Chatman, L., Till, S.R., Kuriyama, Y., Simmen, F.A., Oh, P.S. 2004. Sub-fertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the kruppel-like factor 9/basic transcription element binding protein-1 (bteb1) gene. Journal of Biological Chemistry. 279(28):29286-29294.

Interpretive Summary: Progesterone is a steroid hormone produced primarily by the ovary and is involved in many different biological processes. It is required for the establishment and maintenance of pregnancy and is implicated in the inhibition of abnormal growth processes that could lead to cancer. Progesterone exerts its biological effects by biding to a protein in cells; this is called progesterone receptor. Progesterone receptor in turn can bind other proteins, which amplifies or inhibits the activity of progesterone. In the present study we showed that binding of progesterone receptor to a protein called Basic Transcription Element Binding (BTEB) Protein is important for reproduction and embryo and fetal survival, using a mutant mouse where the gene for the BTEB1 gene is ablated. This study has important applications for understanding the biology of the mammary gland and the uterus, tissues whose normal growth and differentiation are regulated by progesterone as well as dietary and other nutritional factors.

Technical Abstract: Progesterone Receptor (PR), a ligand-activated transcription factor, is a key regulator of cellular proliferation and differentiation in reproductive tissues. The transcriptional activity of PR is influenced by co-regulatory proteins typically expressed in a tissue- and cell-specific fashion. We previously demonstrated that Basic Transcription Element Binding protein-1 (Bteb1), a member of the Sp/Kruppel-like family of transcription factors functionally interacts with the two PR isoforms PR-A and PR-B to mediate progestin-sensitivity of target genes in endometrial epithelial cells in vitro. Here we report that ablation of the Bteb1 gene in female mice results in uterine hypoplasia, reduced litter size, and increased incidence of neonatal deaths in offspring. The reduced litter size is solely a maternal genotype effect, and results from fewer numbers of implantation sites, rather than defects in ovulation. In the early pregnant uterus, Bteb1 expression in stromal cells temporally coincides with PR-A isoform-dependent decidual formation at the time of implantation. Expression of two implantation-specific genes, Hoxa10 and cyclin D3, was decreased in uteri of early pregnant Bteb1-null mutants, while that of Bteb3, a related family member was increased, the latter possibly compensating for the loss of Bteb1. Progesterone responsiveness of several uterine genes was altered with Bteb1 null mutation. These results identify Bteb1 as a functionally relevant PR interacting protein and suggest its selective modulation of cellular processes that are regulated by PR-A in the uterine stroma.