title: Expression of receptors for luteinizing hormone, gastric-inhibitory polypeptide, and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs.
abstract: Hypercortisolism caused by an adrenocortical tumor (AT) results from adrenocorticotropic hormone (ACTH)-independent hypersecretion of glucocorticoids. Studies in humans demonstrate that steroidogenesis in ATs may be stimulated by ectopic or overexpressed eutopic G protein-coupled receptors. We report on a screening of 23 surgically removed, cortisol-secreting ATs for the expression of receptors for luteinizing hormone (LH), gastric-inhibitory polypeptide (GIP), and vasopressin (V(1a), V(1b), and V(2)). Normal adrenal glands served as control tissues. Abundance of mRNA for these receptors was quantified using quantitative polymerase chain reaction (QPCR), and the presence and localization of these receptors were determined by immunohistochemistry. In both normal adrenal glands and ATs, mRNA encoding for all receptors was present, although the expression abundance of the V(1b) receptor was very low. The mRNA expression abundance for GIP and V(2) receptors in ATs were significantly lower (0.03 and 0.01, respectively) than in normal adrenal glands. The zona fasciculata of normal adrenal glands stained immunonegative for the GIP receptor. In contrast, islands of GIP receptor-immunopositive cells were detected in about half of the ATs. The zona fasciculata of both normal adrenal glands and AT tissue were immunopositive for LH receptor; in ATs in a homogenous or heterogenous pattern. In normal adrenal glands, no immunolabeling for V(1b)R and V(2) receptor was present, but in ATs, V(2) receptor-immunopositive cells were detected. In conclusion, QPCR analysis did not reveal overexpression of LH, GIP, V(1a), V(1b), or V(2) receptors in the ATs. However, the ectopic expression of GIP and V(2) receptor proteins in tumorous zona fasciculata tissue may play a role in the pathogenesis of canine cortisol-secreting ATs.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. S.Galac@uu.nl <S.Galac@uu.nl>
authors.forename: S
authors.initials: S
authors.lastname: Galac
authors.forename: V J
authors.initials: VJ
authors.lastname: Kars
authors.forename: S
authors.initials: S
authors.lastname: Klarenbeek
authors.forename: K J
authors.initials: KJ
authors.lastname: Teerds
authors.forename: J A
authors.initials: JA
authors.lastname: Mol
authors.forename: H S
authors.initials: HS
authors.lastname: Kooistra
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000662:veterinary*; D000311:Adrenal Glands / Q000737:chemistry; D000315:Adrenalectomy; D000818:Animals; D004283:Dog Diseases / Q000378:metabolism* / Q000601:surgery; D004285:Dogs; D015870:Gene Expression; D006854:Hydrocortisone / Q000378:metabolism*; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011964:Receptors, Gastrointestinal Hormone / Q000032:analysis / Q000235:genetics*; D011974:Receptors, LH / Q000032:analysis / Q000235:genetics*; D017483:Receptors, Vasopressin / Q000032:analysis / Q000235:genetics*; D015383:Zona Fasciculata / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; D011974:Receptors, LH; D017483:Receptors, Vasopressin; C041086:gastric inhibitory polypeptide receptor; D006854:Hydrocortisone