Thyroid Hormones Decrease Plasma 1a,25-Dihydroxyvitamin D Levels

Somewhat ironic that we see this very detailed explanation of why "active" vitamin D is low in HYPERthyroid people, while the most common story here is of HYPOthyroid people having low vitamin D!

As so often, the work was done in mice. Be good to know if the same is true in humans.

Endocrinology. 2013 Jan 10. [Epub ahead of print]

Thyroid Hormones Decrease Plasma 1a,25-Dihydroxyvitamin D Levels Through Transcriptional Repression of the Renal 25-Hydroxyvitamin D3 1a-Hydroxylase Gene (CYP27B1).

Kozai M, Yamamoto H, Ishiguro M, Harada N, Masuda M, Kagawa T, Takei Y, Otani A, Nakahashi O, Ikeda S, Taketani Y, Takeyama KI, Kato S, Takeda E.

Source

Departments of Clinical Nutrition (M.K., H.Y., M.I., M.M., T.K, Y.Takei., A.O., O.N., S.I., Y.Taket., E.T.) and Nutrition and Metabolism (N.H.), Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503 Japan; and Institute of Molecular and Cellular Biosciences (K.T., S.K.), the University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.

Abstract

The primary determinant of circulating 1a,25-dihydroxyvitamin D (1,25[OH](2)D) levels is the activity of 25-hydroxyvitamin D-1a-hydroxylase (cytochrome P450 27B1 [CYP27B1]) in the kidney. Hyperthyroid patients have been reported to have low levels of plasma 1,25(OH)(2)D. However, the detailed mechanism of thyroid hormone action on vitamin D metabolism is still poorly understood. The present study determined whether renal CYP27B1 gene expression was negatively regulated by thyroid hormones. T(3)-induced hyperthyroid mice showed marked decreases in plasma 1,25(OH)(2)D levels and in renal expression of CYP27B1 mRNA but no changes in plasma concentrations of calcium, PTH, or fibroblast growth factor-23. In addition, we observed that T(3) administration significantly decreased plasma 1,25(OH)(2)D and renal CYP27B1 mRNA levels that were increased by low-calcium or low-phosphorus diets and induced hypocalcemia in mice fed a low-calcium diet. Promoter analysis revealed that T(3) decreases the basal transcriptional activity of the CYP27B1 gene through thyroid hormone receptors (TRa and TRß1) and the retinoid X receptor a (RXRa) in renal proximal tubular cells. Interestingly, we identified an everted repeat negative thyroid hormone response element (1a-nTRE) overlapping the sterol regulatory element (1a-SRE) and the TATA-box -50 to -20 base pairs from the human CYP27B1 gene transcription start site. Finally, we established that CYP27B1 gene transcription is positively regulated by SRE-binding proteins and that a T(3)-bound TRß1/RXRa heterodimer inhibits SRE-binding protein-1c-induced transcriptional activity through the 1a-nTRE. These results suggest that transcriptional repression of the CYP27B1 gene by T(3)-bound TRs/RXRa, acting through the 1a-nTRE, results in decreased renal CYP27B1 expression and plasma 1,25(OH)(2)D levels.

PMID:

23307792

ncbi.nlm.nih.gov/pubmed/233...

Rod

4 Replies

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  • Very interesting indeed.

    My GP reckons everyone this far north is vit D deficient for most of the year, but of course some are more than others.

    I wonder if us thyroidians are more sensitive to being vit D deficient. I must say, taking 5,000 IU daily for a year has done me the world of good, my finger joints are fine again having been very painful. It feels like eating a piece of the sun when you take vit D.

    koala

  • Do you know what your latest Vit D score is?

    My latest score, in Dec, was 99 nmol, I think. The practice manager told me that she'd been told (by the snr GP, whom I've never met) that, as I'm in the optimal Vit D range, I will not be prescribed any more Vit D. The minimum level of the optimal range is 70 nmol. So, unless my Vit D score falls below 70 nmol, they will not accept that I may have insufficient levels of Vit D.

  • HyperT as well as HypoT? Well It's in the news a lot lately - hope folks take notice!

    Still wondering about the chicken and egg thing, Vitamin D & Thyroid probs, meanwhile it works for me - as Koala says eating, but drinking sunshine helps me - only in the morning mind, as taking it later keeps me awake! J :D

    and gov advice

    dh.gov.uk/health/2012/02/vi...

  • Hi there,

    I have hashis and have now been told very low on Vit D and need mega boost once a week. Endocrinologist says that is why I have been having life changing bone pain and feeling really poorly for such a long time. We shall see what happens when I start taking it.

    Cassie

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