Cyclic AMP potentiates growth hormone-dependent differentiation of 3T3-F442A preadipocytes: possible involvement of the transcription factor CREB

Stephen Yarwood, Elaine Kilgour, Neil G. Anderson

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    We have examined the effects of cyclic AMP on the differentiation of 3T3-F442A preadipocytes. High concentrations of intracellular cyclic AMP potently inhibited differentiation whereas low concentrations of intracellular cyclic AMP, induced by a number of different agents, promoted differentiation. To analyse these effects of cyclic AMP more closely, we developed a two-phase protocol for the differentiation of 3T3-F442A cells. Growth hormone (GH) was necessary to prime confluent cells during the first phase, following which, the addition of insulin and other adipogenic agents then promoted terminal differentiation. Cyclic AMP potentiated the priming action of GH but exerted an inhibitory effect on terminal differentiation when added to cells which had previously been primed with GH showing that the effects of cyclic AMP on preadipocyte differentiation are stage-dependent. We analysed the stimulatory effects of cyclic AMP during GH priming and found that cyclic AMP induced phosphorylation of the cyclic AMP response element (CRE) binding protein CREB and activated transcription of a CRE-linked reporter gene. Furthermore, GH also stimulated CREB phosphorylation and activation and this effect was potentiated by cyclic AMP. These results suggest a mechanism for the synergistic priming of preadipocytes for terminal differentiation by cyclic AMP and GH via the activation of differentiation genes containing CREs.

    Original languageEnglish
    Pages (from-to)41-50
    Number of pages10
    JournalMolecular and Cellular Endocrinology
    Volume138
    Issue number1-2
    DOIs
    Publication statusPublished - 16 Mar 1998

    Keywords

    • 1-Methyl-3-isobutylxanthine
    • 3T3 Cells
    • Adipocytes
    • Animals
    • Cell Differentiation
    • Cholera Toxin
    • Colforsin
    • Cyclic AMP
    • Cyclic AMP Response Element-Binding Protein
    • Drug Interactions
    • Glycerolphosphate Dehydrogenase
    • Growth Hormone
    • Ionomycin
    • Isoproterenol
    • Kinetics
    • Mice
    • Recombinant Proteins
    • Thionucleotides
    • Transcription Factors

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