Anti-progestogenic effect of flutamide on uterine expression of calbindin-D9k mRNA and protein in immature mice

Ji, Youn-Kyu; Lee, Geun‐Shik; Choi, Kyung‐Chul; Jeung, Eui‐Bae

doi:10.1016/j.reprotox.2006.04.015

Cited by 9 publications

(10 citation statements)

References 36 publications

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“…We measured the expression of the apoptotic proteins Bax and Bcl-2 in WT, CaBP-9k KO, CaBP-28k KO, and CaBP-9/28k KO mice. Although CaBP-9k protein was not detected in the uteri of immature mice by Western blot analysis in our previous study [Ji et al, 2006], in this study, CaBP-28k protein was detected in the uterine tissue of WT and CaBP-9k KO mice. We also found that apoptosis-related genes were differentially regulated: CaBP-28k KO and CaBP-9/28k KO mice showed significantly higher Bax protein expression compared to WT mice (Fig.…”

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confidence: 75%

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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confidence: 75%

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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“…Where indicated, groups of mice were subjected to a bilateral adrenalectomy (ADX) and/or an ovariectomy (OVX) at 8.5 wk of age and then allowed to heal for 1 wk before treatment (25). To determine the effect of steroid receptor antagonists on renal NCKX3 expressions, flutamide (5 mg/kg), RU486 (10 mg/kg), and ICI 182,780 (10 mg/kg) were injected into male and female ICR mice (17,26,28). To determine the effect of sex steroids on renal NCKX3 expression, estrogen (40 g/kg) and progesterone (4 mg/kg) were injected into male and OVX female mice (17,26,28).…”

Section: Methodsmentioning

confidence: 99%

“…To determine the effect of steroid receptor antagonists on renal NCKX3 expressions, flutamide (5 mg/kg), RU486 (10 mg/kg), and ICI 182,780 (10 mg/kg) were injected into male and female ICR mice (17,26,28). To determine the effect of sex steroids on renal NCKX3 expression, estrogen (40 g/kg) and progesterone (4 mg/kg) were injected into male and OVX female mice (17,26,28). The hormones 1,25(OH) 2D3 (1 g/kg) and PTH (0.1 mg/kg) were administered to male and female mice (5,18,42,45), and aldosterone (1.25 mg/kg) and hydrocortisone (12 mg/kg) were injected into ADX and/or OVX mice (40).…”

Section: Methodsmentioning

confidence: 99%

K⁺-dependent Na⁺/Ca²⁺exchanger 3 is involved in renal active calcium transport and is differentially expressed in the mouse kidney

Lee¹,

Choi²,

Jeung³

2009

American Journal of Physiology-Renal Physiology

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Previously, we reported that renal active calcium-transporting genes are highly expressed in female mice and suggested that renal calcium-processing genes play a critical role in normal calcium reabsorption in females (Lee GS, Lee KY, Choi KC, Ryu YH, Paik SG, Oh GT, Jeung EB. J Bone Miner Res 22: 1968–1978, 2007). In the current study, we evaluated the differential expression of renal calcium-processing genes in male and female mice. Using microarray analysis, we identified K+-dependent Na+/Ca2+ exchanger 3 ( NCKX3) as a gene that was differentially expressed in the kidneys of female and male mice. The expression levels of renal NCKX3 mRNA and protein were higher in female than in male mice, whereas there was no difference between the genders in the levels of NCKX3 expression in the brain. Renal NCKX3 localized to the basolateral layer of distal convoluted tubules, indicating that this protein participates in renal calcium reabsorption. To identify putative regulators in the gender-specific expression of NCKX3, several hormones were injected into mature female and male mice. Although any hormones did not alter NCKX3 expression, adrenal gland-secreted hormones aldosterone and hydrocortisone did downregulate renal NCKX3 mRNA expression in female mice, but they did not change its protein levels. Taken together, the results in this study suggest that a high level of renal NCKX3 expression maintain in distal convoluted tubules may play a role in active calcium transport in the kidneys of female mice.

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“…Flutamide is a non‐steroidal anti‐androgen agent similar to androgens and thus its structure binds the receptor and blocks it. Also, this produces a blockade of the negative feedback exerted by testosterone on the hypothalamus, producing increased plasma levels of LH and testosterone . The pure anti‐androgen flutamide has no intrinsic steroid activity.…”

Section: Introductionmentioning

confidence: 99%

“…Its mechanism of action is believed to be androgen receptor antagonist. It is used in the treatment of human metastatic prostate cancer combined with analogues of LH‐RH, or if the cancer does not respond despite treatment with androgen ablation . In canine prostate cancer it is also used as an effective treatment with minimal adverse clinical response …”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo effect of flutamide on steroid hormone secretion in canine and human inflammatory breast cancer cell lines

Cáceres

Monsalve

Peña

et al. 2017

Vet Comparative Oncology

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The aim was to study the effects of flutamide on cell proliferation, in vivo tumour growth and steroid production in canine and human IBC cell lines. IPC-366 and SUM149 cell cultures were exposed to flutamide concentrations for 72 hours. Additionally, IPC-366 and SUM149 xenotransplanted mice were treated subcutaneously with flutamide 3 times a week for 2 weeks. Steroid hormones determination in culture media, serum and tumour homogenates (pregnenolone, progesterone, androstenedione, testosterone, dihydrotestosterone, 17β-oestradiol and oestrone sulphate) were assayed by EIA. in vitro cell proliferation percentages showed a decrease in all flutamide dosages in IPC-366 and SUM149. in vivo flutamide reduced tumour size by 55% to 65%, and metastasis rates decreased. In treated groups, androgen levels in culture media, serum and tumour homogenates were increased as oestrogen levels decreased. These results suggest that flutamide treatment inhibits cell proliferation and promotes tumour reduction by increasing androgen levels and also support future therapy approaches.

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Anti-progestogenic effect of flutamide on uterine expression of calbindin-D9k mRNA and protein in immature mice

Cited by 9 publications

References 36 publications

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

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

K⁺-dependent Na⁺/Ca²⁺exchanger 3 is involved in renal active calcium transport and is differentially expressed in the mouse kidney

In vitro and in vivo effect of flutamide on steroid hormone secretion in canine and human inflammatory breast cancer cell lines

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Anti-progestogenic effect of flutamide on uterine expression of calbindin-D9k mRNA and protein in immature mice

Cited by 9 publications

References 36 publications

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

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

K+-dependent Na+/Ca2+exchanger 3 is involved in renal active calcium transport and is differentially expressed in the mouse kidney

In vitro and in vivo effect of flutamide on steroid hormone secretion in canine and human inflammatory breast cancer cell lines

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Product

Resources

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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

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

K⁺-dependent Na⁺/Ca²⁺exchanger 3 is involved in renal active calcium transport and is differentially expressed in the mouse kidney