laboratory is interested in how vitamin D regulates the
transcription of target genes. Specifically, we are looking at how
this steroid hormone and its receptor are able to repress
transcription of the parathyroid hormone, a key regulator of calcium
homeostasis in the body. Thus far, we have been able to identify
DNA sequences within the promoter regions of the rat and chicken
parathyroid hormone genes that confers the repressive
transcriptional effects of the hormone. Interestingly, a two
base-pair change in the chicken DNA sequence is able to reverse the
inherent repressive effect to yield an enhancer sequence with
increased transcriptional activity. Our research is now focused on
identifying additional co-factors that interact with the
hormone-receptor-DNA complex to repress transcription of the
parathyroid hormone gene.
Alimov, A. P., Langub, M.C., Malluche, H.H., Koszewski, N.J.
Identification of an Sp1-like DNA element in the PTH promoter.
Endocrinology 144:3138-3147, 2003.
Rowan, A., Koszewski,
N.J. Heterodimer requirement for negative gene regulation by
vitamin D in variant OK cells. Steroids 68:307-314, 2003.
Langub, M.C., Monier-Faugere, M.C.,
Wang, G., Williams, J.P., Koszewski, N.J., Malluche, H.H.
Administration of PTH-(7-84) antagonizes the effects of PTH-(1-84)
on bone in rats with moderate renal failure. Endocrinology
Monier-Faugere, MC, Koszewski, NJ. Use and indication of vitamin D
and vitamin D analogues in patients with renal bone disease. Nephrol
Dial Transplant 17 Suppl 10:6-9, 2002.
Malluche HH, Mawad H,
Koszewski NJ. Update on vitamin D and its newer analogues: Actions
and rationale for treatment in chronic renal failure. Kidney Int