d -Amino acids in mammalian endocrine tissues
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INVITED REVIEW
d‑Amino acids in mammalian endocrine tissues Gabriella Chieffi Baccari1 · Sara Falvo1 · Alessandra Santillo1 · Federica Di Giacomo Russo1 · Maria Maddalena Di Fiore1 Received: 20 July 2020 / Accepted: 7 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract d-Aspartate, d-serine and d-alanine are a regular occurrence in mammalian endocrine tissues, though in amounts varying with the type of gland. The pituitary gland, pineal gland, thyroid, adrenal glands and testis contain relatively large amounts of d-aspartate in all species examined. d-alanine is relatively abundant in the pituitary gland and pancreas. High levels of d-serine characterize the hypothalamus. d-leucine, d-proline and d-glutamate are generally low. The current knowledge of physiological roles of d-amino acids in endocrine tissues is far from exhaustive, yet the topic is attracting increasing interest because of its potential in pharmacological application. d-aspartate is known to act at all levels of the hypothalamus–pituitary–testis axis, playing a key role in reproductive biology in several vertebrate classes. An involvement of d-amino acids in the endocrine function of the pancreas is emerging. d-Aspartate has been immunolocalized in insulin-containing secretory granules in INS-1 E clonal β cells and is co-secreted with insulin by exocytosis. Specific immunolocalization of d-alanine in pituitary ACTH-secreting cells and pancreatic β-cells suggests that this amino acid participates in blood glucose regulation in mammals. By modulating insulin secretion, d-serine probably participates in the control of systemic glucose metabolism by modulating insulin secretion. We anticipate that future investigation will significantly increase the functional repertoire of d-amino acids in homeostatic control. Keywords d-Amino acids · d-Alanine · d-Serine · d-Aspartate · Endocrine glands Abbreviations α-MSH α-Melanocyte-stimulating hormone ACTH Adrenocorticotropic hormone AMPAR α-Amino-3-hydroxy-5-methyl-4isoxazolepropionic acid receptor ATPase Adenosine triphosphatase Ca2+ Calcium d-Ala d-Alanine d-Asp d-Aspartate d-Glu d-Glutamate d-Leu d-Leucine d-Pro d-Proline d-Ser d-Serine d-Allo-Thr d-Allo-threonine d-Thr d-threonine Handling editor: J. D. Wade. * Maria Maddalena Di Fiore [email protected] 1
Dip. Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università della Campania “Luigi Vanvitelli”, Via Vivaldi, 43, 81100 Caserta, Italy
DAAM1 Disheveled-associated-activator of morphogenesis1 d-Amino acid oxidase DAO DDO d-Aspartate oxidase ERK Extracellular signal-regulated kinases GABA γ-Aminobutyric acid GH Growth hormone GluR Glutamate receptor GnRH Gonadotropin-releasing hormone NMDA N-Methyl-d-aspartate NMDAR N-Methyl-d-aspartate receptor l-Asp l-Aspartate LEA/Sen Long–Evans Agouti/SENDAI LH Luteinizing hormone LHRH Luteinizing-hormone-releasing hormone NOS Nitric oxide synthase POMC Pro-opiomelanocortin PREP Prolyl endopeptidase PRL
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