title: Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.
abstract: The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease.
authors.affiliation: Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: hiroki.vet101@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yogo
authors.affiliation: Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kanno
authors.affiliation: Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000737:chemistry / Q000378:metabolism / Q000662:veterinary*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000032:analysis / Q000235:genetics*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000032:analysis / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000032:analysis / Q000235:genetics; D052680:Corticotrophs / Q000737:chemistry; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D015870:Gene Expression; D006801:Humans; D008297:Male; D047748:Pituitary ACTH Hypersecretion; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D052684:Thyrotrophs / Q000737:chemistry
chemical_list: D055415:Bone Morphogenetic Protein 4; D012333:RNA, Messenger; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: Bone morphogenetic protein 4; Bone morphogenetic protein receptor; Canine Cushing's disease