Parathyroid hormone induces the NR4A family of nuclear orphan receptors in vivo

Flavia Q. Pirih, Tara L. Aghaloo, Olga Bezouglaia, Jeanne Nervina, Sotirios Tetradis

Research output: Contribution to journalArticle

Abstract

Parathyroid hormone (PTH) has both anabolic and catabolic effects on bone metabolism, although the molecular mechanisms mediating these effects are largely unknown. Among the transcription factors induced by PTH in osteoblasts are the nerve growth factor-inducible factor B (NR4A; NGFI-B) family of orphan nuclear receptors: Nurr1, Nur77, and NOR-1. PTH induces NR4A members through the cAMP-protein kinase A (PKA) pathway in vitro. We report here that PTH rapidly and transiently induced expression of all three NR4A genes in PTH-target tissues in vivo. In calvaria, long bones, and kidneys, NR4A induction was maximal 0.5-1 h after a single intraperitoneal (i.p.) injection of 80 μg/kg PTH. Nur77 demonstrated the highest expression, followed, in order, by Nurr1 and NOR-1. In calvaria and long bone, PTH-induced expression of each NR4A gene was detectable at 10 μg/kg i.p. with maximum induction at 40-80 μg/kg. PTH (3-34) did not induce NR4A mRNA levels in calvaria, long bone, and kidney in vivo, confirming our in vitro results that NR4A genes are induced primarily through the cAMP-PKA pathway. The magnitude of PTH-induced NR4A expression was comparable in vivo and in vitro. However, NR4A mRNA levels peaked and returned to baseline faster in vivo. Both in vivo and in vitro, PTH induced NR4A pre-mRNA levels suggesting that induction of these genes is, at least in part, through activation of mRNA synthesis. The in vivo induction of the NR4A family members by PTH suggests their involvement in, at least some, PTH-induced changes in bone metabolism.

Original languageEnglish (US)
Pages (from-to)494-503
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume332
Issue number2
DOIs
StatePublished - Jul 1 2005

Fingerprint

Orphan Nuclear Receptors
Parathyroid Hormone
Bone
Bone and Bones
Genes
Skull
Cyclic AMP-Dependent Protein Kinases
Metabolism
Messenger RNA
Nuclear Receptor Subfamily 4, Group A, Member 2
Nuclear Receptor Subfamily 4, Group A, Member 1
Kidney
Anabolic Agents
RNA Precursors
Osteoblasts
Nerve Growth Factor
Intraperitoneal Injections
Transcription Factors

Keywords

  • In vivo
  • NGFI-B
  • NR4A
  • Nuclear orphan receptors
  • Osteoblasts
  • PTH

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Parathyroid hormone induces the NR4A family of nuclear orphan receptors in vivo. / Pirih, Flavia Q.; Aghaloo, Tara L.; Bezouglaia, Olga; Nervina, Jeanne; Tetradis, Sotirios.

In: Biochemical and Biophysical Research Communications, Vol. 332, No. 2, 01.07.2005, p. 494-503.

Research output: Contribution to journalArticle

Pirih, Flavia Q. ; Aghaloo, Tara L. ; Bezouglaia, Olga ; Nervina, Jeanne ; Tetradis, Sotirios. / Parathyroid hormone induces the NR4A family of nuclear orphan receptors in vivo. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 332, No. 2. pp. 494-503.
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