Embryonic osteocalcin signaling determines lifelong adrenal steroidogenesis and homeostasis in the mouse.

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  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
      Original Publication: New Haven [etc.] American Society for Clinical Investigation.
    • Subject Terms:
      Homeostasis* ; Signal Transduction*; Adrenal Glands/*embryology ; Hypothalamo-Hypophyseal System/*embryology ; Osteocalcin/*metabolism ; Pituitary-Adrenal System/*embryology; Animals ; Female ; Glucocorticoids/genetics ; Glucocorticoids/metabolism ; Macaca mulatta ; Mice ; Mice, Knockout ; Osteocalcin/genetics
    • Abstract:
      Through their ability to regulate gene expression in most organs, glucocorticoid (GC) hormones influence numerous physiological processes and are therefore key regulators of organismal homeostasis. In bone, GC hormones inhibit expression of the hormone Osteocalcin for poorly understood reasons. Here, we show that in a classical endocrine feedback loop, osteocalcin in return enhanced the biosynthesis of GC as well as mineralocorticoid hormones (adrenal steroidogenesis) in rodents and primates. Conversely, inactivation of osteocalcin signaling in adrenal glands significantly impaired adrenal growth and steroidogenesis in mice. Embryo-made osteocalcin was necessary for normal Sf1 expression in fetal adrenal cells and adrenal cell steroidogenic differentiation and therefore determined the number of steroidogenic cells present in the adrenal glands of adult animals. Embryonic, not postnatal, osteocalcin also governed adrenal growth, adrenal steroidogenesis, blood pressure, electrolyte equilibrium, and the rise in circulating corticosterone levels during the acute stress response in adult offspring. This osteocalcin-dependent regulation of adrenal development and steroidogenesis occurred even in the absence of a functional hypothalamus/pituitary/adrenal axis and explains why osteocalcin administration during pregnancy promoted adrenal growth and steroidogenesis and improved the survival of adrenocorticotropic hormone signaling-deficient animals. This study reveals that a bone-derived embryonic hormone influences lifelong adrenal functions and organismal homeostasis in the mouse.
    • Comments:
      Comment in: Nat Rev Endocrinol. 2022 Mar;18(3):135. (PMID: 34992234)
      Comment in: J Clin Invest. 2022 Feb 15;132(4):. (PMID: 35166237)
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    • Grant Information:
      P01 AG032959 United States AG NIA NIH HHS; R01 HD107574 United States HD NICHD NIH HHS
    • Contributed Indexing:
      Keywords: Bone Biology; Metabolism; Mouse models
    • Accession Number:
      0 (Glucocorticoids)
      104982-03-8 (Osteocalcin)
    • Publication Date:
      Date Created: 20211214 Date Completed: 20220328 Latest Revision: 20220328
    • Publication Date:
      20240105
    • Accession Number:
      PMC8843753
    • Accession Number:
      10.1172/JCI153752
    • Accession Number:
      34905510