Cutting edge: progesterone directly upregulates vitamin d receptor gene expression for efficient regulation of T cells by calcitriol.
J Immunol. 2015 Feb 1;194(3):883-6. doi: 10.4049/jimmunol.1401923. Epub 2014 Dec 29.
Thangamani S1, Kim M1, Son Y1, Huang X2, Kim H1, Lee JH1, Cho J1, Ulrich B1, Broxmeyer HE2, Kim CH3.
1Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907;
2Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202;
3Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907; and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907 chkim at purdue.edu.
The two nuclear hormone receptor ligands progesterone and vitamin D (vit.D) play important roles in regulating T cells. The mechanism that connects these two hormones in regulating T cells has not been established. In this study, we report that progesterone is a novel inducer of vit.D receptor (VDR) in T cells and makes T cells highly sensitive to calcitriol. At the molecular level, the induction by progesterone is mediated by two progesterone receptor-binding elements in the intron region after the first noncoding exon of the human VDR gene. Increased expression of VDR by progesterone allows highly sensitive regulation of T cells by vit.D even when vit.D levels are suboptimal. This novel regulatory pathway allows enhanced induction of regulatory T cells but suppression of Th1 and Th17 cells by the two nuclear hormones. The results have significant ramifications in effective regulation of T cells to prevent adverse immune responses during pregnancy.
DNA Cell Biol. 2015 Mar 31.
1Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine, Weldon School of Biomedical Engineering, Center for Cancer Research, Purdue University , West Lafayette, Indiana.
Progesterone is a steroid hormone that promotes and maintains pregnancy. Vitamin D (vit. D), another steroid hormone, regulates calcium levels and bone health among many of its functions. The two hormones play important roles also in regulating the immune system.
Recently, we discovered that the vitamin D receptor (VDR) is induced in T cells by progesterone. This finding connects the function of progesterone to that of vit. D and suggests that the two steroid hormones cooperate with each other for sequential and effective regulation of the immune system. Potential implications of the regulation in health and disease are discussed.
6 citations in Google Scholar as of Feb 2019
Vitamin D receptor and progesterone receptor protein and gene expression in papillary thyroid carcinomas: associations with histological features.
J Endocrinol Invest. 2017 Dec;40(12):1327-1335. doi: 10.1007/s40618-017-0700-4. Epub 2017 Jun 6.
Yavropoulou MP1, Panagiotou G2, Topouridou K1, Karayannopoulou G3, Koletsa T3, Zarampoukas T4, Goropoulos A5, Chatzaki E6, Yovos JG1, Pazaitou-Panayiotou K7.
PURPOSE: Vitamin D receptor (VDR) and progesterone receptor (PR) expression has been described in papillary thyroid carcinoma (PTC) but data regarding association with tumor histological characteristics and localization of the protein expression are scarce.
MATERIALS AND METHODS:
Formalin-fixed, paraffin-embedded specimens from 45 patients with PTC (cases) were retrieved and tumor histological data were recorded. We analyzed gene and protein expression of VDR and PR and gene expression of vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzymes in follicular cancer cells and the adjacent non-neoplastic thyroid tissue (NNTT).
VDR mRNA and protein expression was higher in PTC compared with NNTT (p < 0.05). The protein was globally localized in the cytoplasm and cell membranes of the neoplastic cells in all cases, with differences in intensity. Cytoplasmic positivity was stronger in the majority of cases. Membranous positivity was also evident in cases, whereas in NNTT was generally weak and in a low percentage of the cells. Expression of CYP 24A1, but not CYP27B1, was increased in approximately all PTC specimens and was associated with lymph node metastasis and extrathyroidal extension. PR mRNA was increased in 34% and protein expression was present in 57% of cases, and none of NNTT. PR, but not VDR, mRNA expression was significantly associated with the tumor size (r = 0.645, p = 0.007).
We provide evidence for the expression pattern of VDR, PR and CYP24A1 in the progression of PTC. Rapid anti-tumor responses of vitamin D in PTC may be blocked due to inactivation of local vitamin D metabolism.
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- Telomeres (which extend life) appear to be extended by Vitamin D - March 2015
- Traumatic brain injury treated by Vitamin D Progesterone Omega-3 and glutamine – May 2013
- The vitamin D receptor and T cell function – June 2013
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Vitamin D Receptor table shows what compensates for low VDR activation
Compensate for poor VDR by increasing one or more:
|1) Vitamin D supplement|
Sun, Ultraviolet -B
| Vitamin D in the blood |
and thus to the cells
|2) Magnesium||Vitamin D in the blood |
AND to the cells
|3) Omega-3||Vitamin D to the cells|
|4) Resveratrol||Vitamin D to the cells|
|5) Intense exercise||Vitamin D Receptor|
|6) Get prescription for VDR activator|
|Vitamin D Receptor|
|7) Quercetin (flavonoid)||Vitamin D Receptor|
|8) Zinc is in the VDR||Vitamin D Receptor|
|9) Boron||Vitamin D Receptor ?, |
|10) Essential oils e.g. ginger, curcumin||Vitamin D Receptor|
|11) Progesterone||Vitamin D Receptor|
Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation.
You might feel the benefit within days of adding one or more of the above
This page was renamed Feb 2019.
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