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

An, Beum‐Soo; Choi, Kyung‐Chul; Hong, Eui‐Ju; Jung, Yong-Woo; Manabe, Noboru; Jeung, Eui‐Bae

doi:10.1262/jrd.50.445

Cited by 19 publications

(9 citation statements)

References 33 publications

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“…In duodenum, CaBP-9k and TRPV6 were shown to have a similar expression pattern; however, uterine CaBP-9k is regulated by different hormones and expressed at different stages of the estrous cycle (5,25). The expression of CaBP-9k is increased by E2 and at estrus in rats but its expression pattern is controlled by P4 and unaffected at diestrus in mice (1,12). In our previous study, uterine TRPV6 expression in rats was found to be similar to that of CaBP-9k expression in mice (10).…”

Section: Discussionmentioning

confidence: 99%

Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model

Lee¹,

Jeung²

2007

American Journal of Physiology-Endocrinology and Metabolism

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Maintenance of uterine calcium balance is crucial for physiological functioning, including smooth muscle contraction and embryo implantation. Although calbindins were previously thought to act as important uterine calciumprocessing genes for female reproductive function, they were not enough to attest the roles of calcium ions in the reproductive organs. Previously, we reported that rat transient receptor potential cation channel, subfamily V, member 6 (TRPV6) was expressed and regulated by hormones in the uterus. In the present study, we observed uterine TRPV6 expression in a mouse model to clarify the mutual roles of these two calcium-processing genes in female reproductive organs. We investigated uterine TRPV6 mRNA expression during the estrous cycle and pregnancy, as well as its regulation by the steroid hormones estrogen (E2) and progesterone (P4) in mice. Uterine TRPV6 mRNA levels increased at estrus and fluctuated in the uterus, placenta, and fetal membrane during pregnancy. Uterine TRPV6 mRNA increased in mid-and late pregnancy, and its expression was strongly induced in midpregnancy in the labyrinth and spongy zones of the placenta, and in the fetal membrane. E2 (17␤-estradiol) was found to regulate uterine TRPV6 expression in the luminal and glandular epitheliums. In addition, we determined that ER␣ tightly regulated uterine TRPV6 transcription. Together, these results suggest that for uterine function in normal pregnancy, TRPV6 is regulated by E2 via an ER␣-dependent pathway.estrogen receptor-␣; uterus IN MAMMALS, CALCIUM IONS may be involved in control of uterine muscle contraction and embryo implantation. The balance between contraction and relaxation is extremely important throughout pregnancy and during labor. However, regulation of uterine calcium is not yet fully understood. A model for calcium ions in intestinal cells suggests that calcium flows into the cytoplasm via channel proteins, i.e., calcium transporters. These transporters transfer calcium using calcium-binding proteins (Calbindin-D9k or -28k), which are extruded from the cell membrane by a plasma membrane Ca 2ϩ ATPase (28, 31). Transient receptor potential vanilloid type 5 (TRPV5) and 6 (TRPV6) are found in the apical membranes of intestinal and renal epithelial cells and have been proposed as mediators for calcium uptake during trans-cellular transport (7). TRPV6 is also known as epithelial calcium channel 2 (EcaC2) and calcium transporter 1 (CaT1); TRPV5 is also called EcaC1 and CaT2. These closely related proteins are expressed primarily in cells of the duodenum and kidney that are involved in calcium absorption or reabsorption (25). TRPV6 was first cloned from rat duodenum and was detected subsequently in both human and mouse duodena (12,22). The genes encoding these proteins are located closely together on the same chromosome and their genomic structures are similar (12,19,20). TRPV6 is expressed in the duodenum, jejunum, ileum, kidney, and exocrine tissues such as the pancreas, prostate, mammary, and sweat glands (7,12,29,32). I...

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Section: Discussionmentioning

confidence: 99%

Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model

Lee¹,

Jeung²

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Another reason for infertility in the knockout mice is abnormal ovarian function. The ovary is affected by changes in estrogen levels that induce cyclic ovulation [33]. Estrogen stimulates follicular responses to gonadtropins and activities of enzymes such as aromatase for steroidogenesis [34].…”

Section: Reproductive Organsmentioning

confidence: 99%

Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse

2012

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Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) α or ERβ in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERα and ERβ have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERα and ERβ function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.

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“…Instead, uterine CaBP9k and CaBP-28k are regulated by sex steroid hormones in rats [L'Horset et al, 1990[L'Horset et al, , 1993. In a previous report, P4 was shown to enhance CaBP-9k expression in the uteri of oophorectomized adult mice, whereas E2 had no effect [Tatsumi et al, 1999;An et al, 2004a]. In immature mice, it was shown that E2 induced the downregulation of uterine CaBP-28k expression [Opperman et al, 1992].…”

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confidence: 96%

“…In immature mice, it was shown that E2 induced the downregulation of uterine CaBP-28k expression [Opperman et al, 1992]. CaBP-9k is expressed at high levels in the mouse uterus in diestrus and metoestrus, and at basal levels in proestrus and estrus [Nie et al, 2000;An et al, 2004a]. CaBP-28k is expressed at high levels in human uteri in the mid-secretory phase.…”

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confidence: 99%

Apoptosis‐ and endoplasmic reticulum stress‐related genes were regulated by estrogen and progesterone in the uteri of calbindin‐D_9kand ‐D_28kknockout mice

Jung

Choi

et al. 2011

J of Cellular Biochemistry

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Calcium (Ca(2+)) is an important regulator of apoptotic signaling. Calbindin-D(9k) (CaBP-9k) and -D(28k) (CaBP-28k) have a high affinity for Ca(2+) ions. Uterine calbindins appear to be involved in the regulation of myometrial activity by intracellular Ca(2+). In addition, uterine calbindins are expressed in the mouse endometrium and are regulated by steroid hormones during implantation and development. The aim of the present study was to evaluate the regulation of apoptosis in the uteri of CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice. Our findings indicated that Bax protein was enhanced in the uteri of CaBP-28k and CaBP-9k/28k KO mice compared to wild-type (WT) and CaBP-9k KO mice, but no difference was observed in Bcl-2 protein expression. The expressions of caspase 3, 6, and 7 proteins were higher in both CaBP-28k and CaBP-9k/28k KO mice than in WT and CaBP-9k KO mice. These results suggest that the absence of CaBP-28k increases apoptotic signaling. We also investigated the expression of endoplasmic reticulum (ER) stress genes by Western blot analysis in calbindin KO mice. C/EBP homologous protein and immunoglobulin heavy chain-binding protein protein levels were elevated in CaBP-28k KO mice compared to WT mice. When immature mice were treated with 17β-estradiol (E2) or progesterone (P4) for 3 days, we found that the expressions of Bax and caspase 3 protein were increased by E2 treatment in WT and CaBP-9k KO mice, and by P4 treatment in CaBP-28k KO mice. These results indicate that CaBP-28k blocks the up-regulation of apoptosis-related genes and ER stress genes, implying that CaBP-28k may decrease the expression of genes involved in apoptosis and ER stress in murine uterine tissue.

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

Cited by 19 publications

References 33 publications

Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model

Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model

Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse

Apoptosis‐ and endoplasmic reticulum stress‐related genes were regulated by estrogen and progesterone in the uteri of calbindin‐D_9kand ‐D_28kknockout mice

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

Cited by 19 publications

References 33 publications

Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model

Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model

Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse

Apoptosis‐ and endoplasmic reticulum stress‐related genes were regulated by estrogen and progesterone in the uteri of calbindin‐D9kand ‐D28kknockout mice

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Apoptosis‐ and endoplasmic reticulum stress‐related genes were regulated by estrogen and progesterone in the uteri of calbindin‐D_9kand ‐D_28kknockout mice