PARENT SESSION
FEMALE REPRODUCTIVE TRACT - B

Wednesday, August 4, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(821) DIFFERENTIAL TRANSCRIPTIONAL AND TRANSLATIONAL REGULATIONS OF CALBINDIN-D9K BY STEROID HORMONES AND THEIR RECEPTORS IN THE UTERUS OF IMMATURE MICE.

An, Beum-Soo¹, Choi, Kyung-Chul², Hong, Eui-Ju ¹, Jung, Yong-Woo ¹, Leung, Peter C. K. ², Jeung, Eui-Bae^{1, 3}, ¹ Laboratory of Veterinary Biochemistry and Molecular Biology, Cheongju, Republic of Korea² Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada³ Xenotransplantation Research Center, Seoul, Republic of Korea

ABSTRACT- Calbindin-D9k (CaBP-9k) is a cytosolic calcium binding protein mainly expressed in the duodenum, placenta and uterus, and intestinal CaBP-9k is regulated by 1, 25-dyhydcroxyvitamin D3. The uterine CaBP-9k is not under the control of vitamin D, but seems to be regulated by sex steroids. In this study, we examined the regulation of CaBP-9k gene at the transcriptional and translational levels, and also localized CaBP-9k protein in the uterus of immature mice. Treatment with progesterone (P4) resulted in the induction of CaBP-9k mRNA, and a co-treatment with estrogen (E2) plus P4 evoked a synergic effect on its mRNA level in this tissue. Interestingly, the translation of CaBP-9k protein was enhanced by E2, while no difference was observed at the transcriptional level by E2. Not only P4 but also E2 itself induced an increase of CaBP-9k protein, and co-treatment with E2 and P4 showed a similar effect on its protein level in the uterus of immature mice. The CaBP-9k protein was localized in the grandular epithelium of stroma in the uterus of immature mice at diestrus, indicating that the expression of CaBP-9k protein could be regulated differentially by sex steroids. A potential mechanism of synergic effect of P4 and E2 may be derived from E2 action in the increase of progesterone receptor (PR), and up-regulated PR may increase P4-induced CaBP-9k expression. This complicating relationship between CaBP-9k and steroid receptors suggests that P4 regulates CaBP-9k gene in the uterus of immature mice, in addition, E2 also can affect the expression of CaBP-9k through the regulation of PR. The expression levels of ER and PR were further examined in this tissue. E2 stimulated the expression levels of ER and PR mRNAs and P4 inhibited the expression of these transcripts at early time point (12 h) and increased them at 24 and 48 h, while co-treatments with both steroids increased transcripts of ER and PR at 24 h. In conclusion, P4 and PR may be a dominant factor in the regulation of CaBP-9k, in addition, E2 and ER can also influence the expression of CaBP-9k gene via an indirect pathway in the uterus of immature mice. [This work was supported by grant R01-2002-000-00015-0 (2002) from the Basic Research Program of the Korea Science & Engineering Foundation]

KEY WORDS: Uterus, Calbindin-D9k, Mouse, Steroid