Expression of genes related to corticotropin production and glucocorticoid feedback in corticotroph adenomas of dogs with Cushing's disease.
Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to negative feedback by glucocorticoids. In this study, we examined gene expression related to adrenocorticotropic hormone (ACTH) production and secretion, and the negative feedback by glucocorticoids in canine corticotroph adenoma. We used resected corticotroph adenomas from 10 dogs with Cushing's disease. In order to investigate the alteration of gene expression between corticotroph adenoma and normal corticotrophic cells, ACTH-positive cells in the anterior lobe were microdissected using a laser-capture microdissection system, and mRNA levels of proopiomelanocortin (POMC), corticotropin releasing hormone receptor 1 (CRHR1), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11 beta hydroxysteroid dehydrogenase (11HSD) type 1 and type 2 were determined using real-time RT-PCR. POMC, CRHR1, and 11HSD2 mRNA levels in corticotroph adenoma were greater than those in normal corticotrophic cells (POMC, 5.5-fold; CRHR1, 4.9-fold; 11HSD2, 4.2-fold, P<0.01, respectively). MR and 11HSD1 mRNA levels in corticotroph adenoma were lower than those in normal corticotrophic cells (MR, 2.2-fold; 11HSD1, 2.9-fold, P<0.01, respectively). GR mRNA levels did not differ between corticotroph adenoma and normal corticotrophic cells. Our results may help to understand the increased ACTH production and the resistance to negative feedback suppression by glucocorticoids in canine corticotroph adenomas. These changes in gene expression may have a role in the growth of canine corticotroph adenoma, and help elucidate the pathophysiology of dogs with Cushing's disease.
Teshima
Takahiro
T
Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
Hara
Yasushi
Y
Takekoshi
Susumu
S
Teramoto
Akira
A
Osamura
Robert Y
RY
Tagawa
Masahiro
M
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics; D049913:ACTH-Secreting Pituitary Adenoma / Q000737:chemistry / Q000235:genetics / Q000662:veterinary*; D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D025461:Feedback, Physiological; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005938:Glucocorticoids / Q000502:physiology*; D008297:Male; D047748:Pituitary ACTH Hypersecretion / Q000235:genetics / Q000662:veterinary*; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000235:genetics / Q000662:veterinary*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D042842:11-beta-Hydroxysteroid Dehydrogenases