In Rat Uterus 17β-Estradiol Stimulates a Calcium-Binding Protein Similar to the Duodenal Vitamin D-Dependent Calcium-Binding Protein

Abstract

A calcium-binding protein (CaBP) similar to rat duodenal vitamin D-dependent CaBP was identified in rat uterus. Uterine CaBP and duodenal CaBP had the same mol wt (9,000-10,000), exhibited the same calcium-dependent electrophoretic mobility, and were immunologically identical. The localization of CaBP in the rat uterus was explored using indirect immunoperoxidase methods, and by CaBP RIA in the endometrium and myometrium after enzyme separation. In the endometrium CaBP was found in the cytoplasm of the stroma cells but not in the epithelium or in the glandular cells. In the myometrium, it was located inside the smooth myometrial fibers. Hormonal regulation of CaBP was shown to differ in the uterus and duodenum. Duodenal CaBP concentrations increased in response to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and were not influenced by ovariectomy or sex steroids administration. By contrast, CaBP synthesis fell drastically in the uterus of ovariectomized rats, but was greatly enhanced by low physiological doses of 17 beta-estradiol. This effect of 17 beta-estradiol on uterine CaBP was dose dependent. Medroxyprogesterone and more especially 1,25(OH)2D3 exerted no such stimulating effect on uterine CaBP. In vitamin D-deficient ovariectomized rats, administration of 17 beta-estradiol alone restored the uterine CaBP concentrations to normal and this potency contrasted with the apparent inability of 1,25(OH)2D3 to affect the uterine CaBP concentrations. Our data suggest that, unlike duodenal CaBP regulation, the expression of the CaBP gene in rat uterus is predominantly controlled by 17 beta-estradiol.

Molecular cloning of the full‐length cDNA encoding the human calbindin‐D9k

“…The CaBP-9k belongs to a family of calcium-binding proteins which includes such proteins as ealmodulin, parvalbumin, troponin C, and S100 protein [2]. CaBP-9k is found in the mammalian intestine [3]~ placenta [4], uterus [5], and kidney [6]. Its exact function is unknown.…”

“…The intestinal CaBP-gk is vitamin D-dependent and its expression correlates with calcium transport activity [7]. A possible role in calcium transport in placenta and kidney has been postulated in a vitamin D-independent fashion [2,6]. Uterine CaBP-gk is transcriptionally regulated by 17fl-estradiol [8°9] with a putative function in control of myometrial activity via intracellular calcium.…”

Role of Vitamin D in Reducing the Risk of Preterm Labour

“…Therefore several studies point to the fact that vitamin D is involved in the regulation of acquired and innate immune responses at the foetal-maternal interface across gestation 22 Vitamin D reduces the risk of SPB also by helping to maintain myometrial quiescence. Myometrial contractility is dependent on calcium release within the muscle cell and this process is regulated by vitamin D. [23][24][25] Poor maternal vitamin D status might also increase risk of caesarean delivery by reducing strength of the pelvic musculature and the mother's ability to push and deliver vaginally leading a reduced ability to push and to a longer and more difficult labour. 26 Mothers with suboptimal vitamin D status have offspring with reduced intrauterine and postnatal skeletal development.…”

Differential Transcriptional and Translational Regulations of Calbindm-D9k by Steroid Hormones and Their Receptors in the Uterus of Immature Mice

“…In the uterus, CaBP-9k is expressed mainly in endometrial stroma and the myometrium of rat [7,14,15]. However, in pregnant rats, it is also expressed in the uterine epithelium [16].…”

“…Functionally, intestinal CaBP-9k is regulated by 1,25-dyhydroxyvitamin D3, the hormonal or of vitamin D [5], and is involved in intestinal calcium absorption [3,6]. However, despite the presence of vitamin D receptors, uterine CaBP-9k is not under the control of vitamin D, but seems to be regulated by the sex steroid hormones [7][8][9][10]. This differential regulation of CaBP-9k is not only limited just to a tissue-specific manner but also extends to a species-specific manner.…”