NK3R Mediates the EGF-Induced SLα Secretion and mRNA Expression in Grass Carp Pituitary

Epidermal growth factor (EGF) is a potent regulator of cell function in many cell types. In mammals, the EGF/EGFR system played an important role in both pituitary physiology and pathology. However, it is not clear about the pituitary action of EGF in lower vertebrates. In this study, using grass carp as a model, we found that EGF could stimulate NK3R mRNA and protein expression through pituitary ErbB1 and ErbB2 coupled to MEK/ERK and PI3K/Akt/mTOR pathways. In addition, EGF could also induce pituitary somatolactin α (SLα) secretion and mRNA expression in a dose- and time-dependent manner in vivo and in vitro. The stimulatory actions of EGF on SLα mRNA expression were also mediated by PI3K/Akt/mTOR and MEK/ERK pathways coupled to ErbB1 and ErbB2 activation. Our previous study has reported that neurokinin B (NKB) could also induce SLα secretion and mRNA expression in carp pituitary cells. In the present study, interestingly, we found that EGF could significantly enhance NKB-induced SLα mRNA expression. Further studies found that NK3R antagonist SB222200 could block EGF-induced SLα mRNA expression, indicating an NK3R requirement. Furthermore, cAMP/PKA inhibitors and PLC/PKC inhibitors could both abolish EGF- and EGF+NKB-induced SLα mRNA expression, which further supported that EGF-induced SLα mRNA expression is NK3R dependent.

[1]  Cheng Ye,et al.  Pituitary Action of E2 in Prepubertal Grass Carp: Receptor Specificity and Signal Transduction for Luteinizing Hormone and Follicle-Stimulating Hormone Regulation , 2018, Front. Endocrinol..

[2]  J. Smitz,et al.  Neurokinin B Exerts Direct Effects on the Ovary to Stimulate Estradiol Production. , 2016, Endocrinology.

[3]  Cheng-Yuan Lin,et al.  Novel pituitary actions of TAC3 gene products in fish model: receptor specificity and signal transduction for prolactin and somatolactin α regulation by neurokinin B (NKB) and NKB-related peptide in carp pituitary cells. , 2014, Endocrinology.

[4]  Koichiro Tamura,et al.  MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. , 2013, Molecular biology and evolution.

[5]  M. Aoyama,et al.  Insight into molecular and functional diversity of tachykinins and their receptors. , 2013, Protein and peptide letters.

[6]  Katsumi Tsukamoto,et al.  Profiles of mRNA expression for prolactin, growth hormone, and somatolactin in Japanese eels, Anguilla japonica: The effect of salinity, silvering and seasonal change. , 2013, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[7]  Yong Zhang,et al.  The evolution of tachykinin/tachykinin receptor (TAC/TACR) in vertebrates and molecular identification of the TAC3/TACR3 system in zebrafish (Danio rerio) , 2012, Molecular and Cellular Endocrinology.

[8]  A. Ibrahim,et al.  Effect of stress during handling, seawater acclimation, confinement, and induced spawning on plasma ion levels and somatolactin-expressing cells in mature female Liza ramada. , 2012, Journal of experimental zoology. Part A, Ecological genetics and physiology.

[9]  S. Fukamachi,et al.  Reassessment of the function of somatolactin alpha in lipid metabolism using medaka mutant and transgenic strains , 2012, BMC Genetics.

[10]  S. Ben-Dor,et al.  Neurokinin Bs and neurokinin B receptors in zebrafish-potential role in controlling fish reproduction , 2012, Proceedings of the National Academy of Sciences.

[11]  S. Melmed,et al.  Expression and function of ErbB receptors and ligands in the pituitary. , 2011, Endocrine-related cancer.

[12]  C. Liebmann EGF receptor activation by GPCRs: An universal pathway reveals different versions , 2011, Molecular and Cellular Endocrinology.

[13]  P. Chanson,et al.  TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. , 2010, The Journal of clinical endocrinology and metabolism.

[14]  S. O’Rahilly,et al.  Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor. , 2009, The Journal of clinical endocrinology and metabolism.

[15]  Frank Reimann,et al.  TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction , 2009, Nature Genetics.

[16]  S. Kansra,et al.  Estrogen receptor-alpha mediates the epidermal growth factor-stimulated prolactin expression and release in lactotrophs. , 2009, Endocrinology.

[17]  W. Ge,et al.  Differential regulation of gonadotropins (FSH and LH) and growth hormone (GH) by neuroendocrine, endocrine, and paracrine factors in the zebrafish--an in vitro approach. , 2009, General and comparative endocrinology.

[18]  H. Kawauchi,et al.  Chapter 5 The Neuroendocrine Regulation of Prolactin and Somatolactin Secretion in Fish , 2009 .

[19]  B. Björnsson,et al.  Cloning of somatolactin alpha, beta forms and the somatolactin receptor in Atlantic salmon: Seasonal expression profile in pituitary and ovary of maturing female broodstock , 2008, Reproductive biology and endocrinology : RB&E.

[20]  Xinyan Wang,et al.  Grass carp somatolactin: II. Pharmacological study on postreceptor signaling mechanisms for PACAP-induced somatolactin-alpha and -beta gene expression. , 2008, American journal of physiology. Endocrinology and metabolism.

[21]  Yong Zhu,et al.  Cloning of somatolactin alpha and beta cDNAs in zebrafish and phylogenetic analysis of two distinct somatolactin subtypes in fish. , 2004, The Journal of endocrinology.

[22]  W. Ge,et al.  Cloning of Epidermal Growth Factor (EGF) and EGF Receptor from the Zebrafish Ovary: Evidence for EGF as a Potential Paracrine Factor from the Oocyte to Regulate Activin/Follistatin System in the Follicle Cells1 , 2004, Biology of reproduction.

[23]  I. Kawase,et al.  Role of extracellular subdomains of p185c-neu and the epidermal growth factor receptor in ligand-independent association and transactivation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Manuel C. Peitsch,et al.  SWISS-MODEL: an automated protein homology-modeling server , 2003, Nucleic Acids Res..

[25]  D. Rees,et al.  Mitogen‐Activated Protein Kinase Mediates Epidermal Growth Factor‐Induced Morphogenesis in Pituitary GH3 Cells , 2002, Journal of neuroendocrinology.

[26]  D. O’Rourke,et al.  The role of distinct p185neu extracellular subdomains for dimerization with the epidermal growth factor (EGF) receptor and EGF-mediated signaling , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  A. Wong,et al.  Somatostatin inhibits (d-Arg6, Pro9-NEt) salmon gonadotropin-releasing hormone- and dopamine D1-stimulated growth hormone release from perifused pituitary cells of chinese grass carp, ctenopharyngodon idellus. , 1998, General and comparative endocrinology.

[28]  D. Stern,et al.  Specificity within the EGF family/ErbB receptor family signaling network , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[29]  D. Verrier,et al.  Identification of epidermal growth factor-secreting cells in the anterior pituitary of lactating female rats. , 1996, The Journal of endocrinology.

[30]  Y. Yarden,et al.  ErbB‐2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. , 1996, The EMBO journal.

[31]  D. Verrier,et al.  EGF release by rat gonadotroph cells: characteristics and effects of LHRH. , 1995, Life sciences.

[32]  K. Kovacs,et al.  Localization of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFr) in human pituitary adenomas and nontumorous pituitaries: An immunocytochemical study , 1996, Endocrine pathology.

[33]  Y. Yarden,et al.  Neu differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and displays a differential requirement for ErbB-2 , 1995, Molecular and cellular biology.

[34]  J. Lestage,et al.  Estrogen increases the release of epidermal growth factor from individual pituitary cells in female rats. , 1995, The Journal of endocrinology.

[35]  J. Lestage,et al.  Epidermal growth factor: a potential paracrine and autocrine system within the pituitary. , 1995, Neuroreport.

[36]  G. Childs,et al.  Epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acids and their receptors in the rat anterior pituitary: localization and regulation. , 1995, Endocrinology.

[37]  G. Unabia,et al.  Corticotropin-releasing hormone and epidermal growth factor: mitogens for anterior pituitary corticotropes. , 1995, Endocrinology.

[38]  G. Childs,et al.  Differential regulation of epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acid in the rat anterior pituitary and hypothalamus induced by stresses. , 1995, Endocrinology.

[39]  N. Hynes,et al.  Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling , 1995, Molecular and cellular biology.

[40]  E. Finley,et al.  Human pituitary somatotropes express transforming growth factor-α and its receptor , 1994 .

[41]  M. Sliwkowski,et al.  Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. , 1994, The Journal of biological chemistry.

[42]  W. Dougall,et al.  Heterodimerization of epidermal growth factor receptor and wild-type or kinase-deficient Neu: a mechanism of interreceptor kinase activation and transphosphorylation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[43]  S. Asa,et al.  Transforming growth factor-α in normal and neoplastic human endocrine tissues , 1992 .

[44]  M. Greene,et al.  Intermolecular association of the p185 neu protein and EGF receptor modulates EGF receptor function , 1990, Cell.

[45]  M. Ono,et al.  cDNA cloning of somatolactin, a pituitary protein related to growth hormone and prolactin. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[46]  L. Kiesel,et al.  Epidermal growth factor stimulates luteinizing hormone and arachidonic acid release in rat pituitary cells , 1988, Molecular and Cellular Endocrinology.

[47]  F. Peillon,et al.  Epidermal growth factor-binding sites, present in normal human and rat pituitaries, are absent in human pituitary adenomas. , 1987, The Journal of clinical endocrinology and metabolism.

[48]  J. Chabot,et al.  Distribution of Epidermal growth factor binding sites in the adult rat anterior pituitary gland , 1986, Peptides.

[49]  N. Kuzuya,et al.  Epidermal growth factor stimulates growth hormone secretion from superfused rat adenohypophyseal fragments. , 1984, Endocrinology.

[50]  B. White,et al.  Epidermal growth factor and thyrotropin-releasing hormone interact synergistically with calcium to regulate prolactin mRNA levels. , 1983, The Journal of biological chemistry.

[51]  R. Evans,et al.  Epidermal growth factor rapidly stimulates prolactin gene transcription , 1982, Nature.