Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia

Rhinos Rhants #3 - The STEROID almost everyone should be taking.

Total RNA was isolated 24 hours later and QRT-PCR was performed to quantitate gene expression. Human CYP24 promoter reporter CYPluc and OC promoter reporter OC-luc were kindly provided by J. Analysis of relative gene expression data using real-time quantitative PCR and the 2 -Delta Delta C T Method. This could be the result of the presence of additional pathways forCYP3A4 regulation. Pregnenolone 16a-carbonitrile does not induce CYP24 expression in vivo, and 1,25 OH 2D3-induced CYP24 expression is enhanced in PXR-knockout mice. Aliquots of lysate were combined with reaction buffer 1 m diethanolamine, pH 9. In addition, 1,25 OH 2D3 treatment was also able to elicit a modest 2.

A study by another research group that also appeared in the JCI reported that activation of SXR induced CYP24 expression in mice, which would explain an increase in vitamin D breakdown and the resulting osteomalacia observed in individuals taking some SXR-activating antiepileptic drugs or antibiotics. Poulton for technical support; Y. Vitamin K2 was first reported to promote fracture healing in 5 , and several studies showed that vitamin K2 is closely associated with increased bone formation 6 , 7 and decreased bone resorption 8 — These studies indicate that SXR functions as a xenobiotic sensor to coordinately regulate drug clearance in the liver and intestine. Prominent expression of SXR mRNA is also found in the intestine Fig.

Said is steroide Professor of Medicine, Steroide aufgequollenes gesicht and Biophysics at the University of California Beste of Medicine Irvine, CA. He is also a Senior Research Career Scientist at the VA Medical Center, Long receptoor CA; and Chairman aand the Muskelaufbau California Muskelaufbaupräparate ohne nebenwirkungen for Research and inaktivierung von steroidhormonen VALBHS tabletten non-profit.

He serves as die reviewer on a variety of NIH, VA and other national study sections as well as testosteron European study sections dealing with medical research in internal medicine and nutrition. He is also a member of Editorial Boards of a number of prestigious medical research journals. Said laboratory focuses on understanding cellular and molecular mechanisms involved in the transport of water-soluble vitamins folate vit.

Bthiamine vit. B1riboflavin vit. B2pyridoxine vit. B6ascorbic acid vit. Cbiotin vit. H and niacin vit. B3 in the intestine, kidney, liver and pancreas. Said's laboratory has published over original research papers in the gastrointestinal and nutrition fields. He has authored many chapters in scientific textbooks as well as a book in these areas. His laboratory has contributed many original discoveries to the field over the years. His research activities are funded by the VA and National Institutes of Health over the past twenty four years.

Admittedly, we cannot exclude the possibility that RIF elicited a transient increase in intestinal CYP24 expression during the 6-hour dose interval, similar to that seen in rats treated acutely with 1,25 OH 2D3 36 — 38 , but the effect would have to have been short lived and discordant with the effect of the SXR agonist on CYP3A4 expression. Total counts were measured using a Topcount scintillation counter Packard Instrument Co. In particular, CYP3A4 has been shown to be inducible by virtually all known SXR activators Figs. Third, compounds known to induce catabolic enzymes should activate the sensor. Second, catabolic enzymes expressed in these tissues should be induced by the sensor.

SXR, a novel steroid and xenobioticsensing nuclear receptor

Table Summary of Class II Nonsteroid Hormone Receptor Proposed Functions , a ER-6 ABCC2 PXR/SXR DR-3, ER-4 Steroid, xenobiotic CYP3A4, vitamin D receptor ; TR, thyroid hormone receptor ; RAR, retinoic acid receptor ;. with vitamin D: A novel approach for enhancing vitamin D nutritional health. Steroid and xenobiotic receptor and vitamin D receptor cross-talk mediates CYP24. Long-term therapy with some antiepileptic drugs and antibiotics can cause osteomalacia, a condition marked by softening of the bones that is.