Vitamin D-Dependent Calcium Binding Protein in Rat Uterus: Differential Effects of Estrogen, Tamoxifen, Progesterone, and Pregnancy on Accumulation and Cellular Localization*

Abstract

The present studies were undertaken to characterize the expression of calcium binding protein (CaBP or calbindin-D9k) in uterine tissues. Using immunohistochemical techniques, calbindin-D9k was localized to the uterine (luminal) epithelium of pregnant rats, but not present in the uterine epithelium of nonpregnant rats. Calbindin was found also in the uterine smooth muscle and endometrial stromal cells of pregnant animals. These latter localizations were reproduced in uteri of 21-day-old nonpregnant rats by administration of tamoxifen or physiological doses of estrogens. Estrogen and tamoxifen produced half-maximal increases of uterine calbindin at daily doses of 0.1 and 10 micrograms, respectively, and maximal responses at 0.3 and 40 micrograms/day. Testosterone and progesterone, at doses which increased the growth of the uterus, did not induce calbindin-D, and both hormones blocked estradiol's effect on uterine calbindin-D appearance. The epithelial localization of calbindin in pregnant uteri was not reproduced in nonpregnant animals by either estradiol (3 micrograms/day) or progesterone (1 mg/day). The localization of calbindin in uterine epithelium during pregnancy appears to be dependent upon an as yet unknown factor. In view of the large surface area of the luminal epithelium in pregnant animals, and the pregnancy-related expression of calbindin in these cells, we propose that uterine epithelium plays an important role in transport of calcium during pregnancy.

Maternal Exposure to Bisphenol A during Late Pregnancy Resulted in an Increase of Calbindin-D9k mRNA and Protein in Maternal and Postnatal Rat Uteri

“…CaBP-9k expression was previously detected mainly in the luminal epithelial cells of the uterus in pregnant rats, but the CaBP-9k gene in non-pregnant rats was mainly expressed in stromal cells of the myometrium and endometrium [41]. Immunohistochemical staining demonstrated that treatment with BPA increased CaBP-9k protein in the maternal uterus, confirming the mRNA level.…”

Estradiol-dependent uterine leiomyomas in transgenic mice.

“…CaBP9K is found in several rat tissues, such as enterocytes, myometrium, and epithelial alveolar cells of the lung (14)(15)(16)(17).The uterine CaBP9K gene is under the positive control of estradiol; the gene is silent in ovariectomized rodents (18,19) and strongly activated after estradiol treatment (20,21). CaBP9K is also expressed in the kidney of the mouse (22,23).…”

Gestational changes in calbindin-D9k in rat uterus, yolk sac, and placenta: implications for maternal-fetal calcium transport and uterine muscle function.

“…The presence of this cytoplasmic protein is a marker for active transcellular calcium transport, and the expression of calbindin-D9k in these epithelial tissues is dependent on the hormonal action of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (7). Calbindin-D9k is also found in uterine myometrium and endometrial stroma of the mature nonpregnant female where both estrogen and progesterone action can control its abundance (8,9). The function of calbindin in uterine muscle is unknown; thus far myometrium is the only muscle found to contain calbindin-D9k.…”

“…Before birth, calbindin-D9k is found in transporting epithelia of the yolk sac and intraplacental yolk sac (IPYS) and in the luminal epithelium of the maternal uterus (9)(10)(11)(12)(13). By analogy to the intestinal and renal epithelia, calbindin-D9k in these epithelial cells is thought to play a role in transcellular calcium movement (9).…”