Estrogen-induced calbindin-D 9k gene expression in the rat uterus during the estrous cycle: late antagonistic effect of progesterone.

Abstract

Progesterone modulates estrogen-stimulated responses in the uterus. Calbindin-D 9k (CaBP9k), a 17 beta-estradiol-responsive gene expressed in the uterus, was used as a marker to examine the interactions between endogenous progesterone and estradiol in the rat. The variations in uterine CaBP9k messenger RNAs (mRNAs) during the rat estrous cycle indicated that CaBP9k gene expression was greatest during the estrogen-dominated phases (proestrus and estrus) and became totally repressed during diestrus, when progesterone predominates. Estradiol was found to be the major controlling factor of CaBP9k gene expression in vivo, progesterone antagonizing estrogen-induced CaBP9k gene expression. The inhibitory role of progesterone was further examined in two experiments. Mature cyclic rats were injected with the progesterone antagonist RU486 before the progesterone surge of proestrus, and the estrous cycle was mimicked in ovariectomized rats by sequential injections of estrogen and progestin. Progesterone did not appear to be involved in the rapid decrease in CaBP9k mRNA during estrus but was implicated in the down-regulation of the estrogen-stimulated CaBP9k gene expression at the end of estrus and during diestrus. This delayed effect of progesterone was confirmed in the ovariectomized rat model. CaBP9k mRNA accumulation in estrogen-primed ovariectomized rats was suppressed by estrogen followed 1 h later by the progesterone agonist R5020. This effect occurred more than 24 h after progestin treatment. The inhibition of the estrogen-induced CaBP9k gene expression in the rat uterus by progesterone is certainly mediated by the progesterone receptor, because progesterone had no effect without estrogen priming or when the antagonist RU486 was used. The delayed progesterone effect probably does not involve depletion of nuclear estrogen receptors, the major rapid mechanism proposed for estrogen inhibition by progesterone in the rodent uterus, or control of estrogen receptor synthesis, as shown by Northern blot analysis of estrogen receptor mRNA.

Immunohistochemical and histochemical identification of proteins and carbohydrates in the equine endometrium: Reaction patterns in the cycling mare

“…Distinct species differences have been reported regarding the regulation of calbindin D9k (CAL) during the estrus cycle. While in bovine (Inpanbutr et al 1994) and murine (Tatsumi et al 1999) endometrium its expression seems to depend on progesterone, a positive influence of estrogen has been shown in the rat endometrium (L´Horset et al 1993). However, there are no reports on its expression in the equine endometrium.…”

Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation

“…In rat uterus it has been previously found that CaBP-d9k expression is under strict estrogen regulation (Dupret et al 1992, Krisinger et al 1993, L'Horset et al 1993. However, high expression of CaBP-d9k in porcine uterus during the luteal phase correlates to the regulation of the progesterone gene in that species, due to the lack of a functional ERE.…”

“…Previous studies have identified that CaBP-d9k is highly expressed in the mouse and rat uterus during early pregnancy (Darwish et al 1991, Krisinger et al 1992, Krisinger et al 1993, L'Horset et al 1993, Tatsumi et al 1999, Nie et al 2000. In the mouse it is differentially expressed between implantation and inter-implantation sites at the time of initial embryo attachment (Nie et al 2000).…”

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

“…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.…”

“…This differential regulation of CaBP-9k is not only limited just to a tissue-specific manner but also extends to a species-specific manner. In the rat uterus, the expression level of CaBP-9k gene is suppressed at diestrus, and increases at proestrus in response to the plasma estrogen levels [8,11]. In ovariectomized rats, estrogen (E2) caused the rapid accumulation of CaBP-9k transcripts in the uterus [9], while progesterone (P4) inhibited the E2-i n d u c e d C a B P -9 k g e n e i n E 2 p r i m e d ovariectomized rat [8].…”