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PMID: 3771798 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat.

The Journal of clinical investigation ·Vol. 78 ·No. 5 ·1986-11-00 ·Pages 1296-301

Silver J, Naveh-Many T, Mayer H, Schmelzer HJ, Popovtzer MM

Abstract

In vitro 1,25-dihydroxycholecalciferol (1,25(OH)2D3) decreased levels of preproparathyroid(preproPTH) hormone mRNA. We have now pursued these studies in vivo in the rat. Rats were administered vitamin D metabolites i.p. and the levels of preproPTH mRNA were determined in excised parathyroid-thyroid glands by blot hybridization. PreproPTH mRNA levels were less than 4% of basal at 48 h after 100 pmol 1,25(OH)2D3, with no increase in serum calcium. Gel blots showed that 1,25(OH)2D3 decreased preproPTH mRNA levels without any change in its size (833 basepair). Microdissected parathyroids after 1,25(OH)2D3 (100 pmol) showed mRNA levels for preproPTH were 40 +/- 8% of controls, but for beta-actin were 100% of controls. The relative potencies of vitamin D metabolites were: 1,25(OH)2D3 greater than 24,25(OH)2D3 greater than 25(OH)D3 greater than vitamin D3. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' PTH transcription was 10% of control, while beta-actin was 100%. These results show that 1,25(OH)2D3 regulates PTH gene transcription. PTH stimulates 1,25(OH)2D3 synthesis, which then inhibits PTH synthesis, thus completing an endocrinological feedback loop.

MeSH Terms
Animals Calcitriol/pharmacology Cell Nucleus/metabolism DNA/metabolism Genes/drug effects Kinetics Male Nucleic Acid Hybridization Parathyroid Glands/drug effects,metabolism Parathyroid Hormone/genetics Protein Precursors/genetics RNA, Messenger/genetics Rats Rats, Inbred Strains Structure-Activity Relationship Transcription, Genetic/drug effects Vitamin D/pharmacology
Chemicals
Parathyroid Hormone Protein Precursors RNA, Messenger Vitamin D preproparathormone DNA Calcitriol
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Silver J
Naveh-Many T
Mayer H
Schmelzer H J
Popovtzer M M
References (27)
27 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112714
Published
1986-11-00
Pages
1296-301
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC423816
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI112714 PMC Full Text View journal details
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