Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

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Author(s)

    • Maliza Rita
    • Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Japan
    • Fujiwara Ken
    • Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Japan
    • Tsukada Takehiro
    • Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Japan
    • Azuma Morio
    • Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Japan
    • Kikuchi Motoshi
    • Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Japan|Laboratory of Natural History, Jichi Medical University School of Medicine, Shimotsuke, Japan
    • Yashiro Takashi
    • Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Japan

Abstract

Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (<i>Ghrh-r</i>), growth hormone secretagogue receptor (<i>Ghs-r</i>) and somatostatin receptors (<i>Sst-rs</i>). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10<sup>-6</sup> M) for 24 h increased gene expression levels of <i>Ghrh-r</i> and <i>Ghs-r</i>; however, expressions of <i>Sst-r2</i> and <i>Sst-r5</i> were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on <i>Ghrh-r</i> and <i>Ghs-r</i> gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of <i>Ghrh-r</i> and <i>Ghs-r</i> are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

Journal

  • Endocrine Journal

    Endocrine Journal 63(6), 555-561, 2016

    The Japan Endocrine Society

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