title: Eutopic overexpression of vasopressin v1a receptor in adrenocorticotropin-independent macronodular adrenal hyperplasia.
abstract: Arginine vasopressin (AVP) stimulates cortisol secretion through its vascular type V(1a) receptor in the adrenal glands, in addition to stimulating ACTH secretion through pituitary V(3) receptor. Because hyper-response of plasma cortisol to vasopressin is documented in some patients with Cushing's syndrome due to adrenal adenoma (CS) or ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), we analyzed the expression of V(1a), V(2), V(3) receptor and AVP mRNA in human adrenal tissues by quantitative competitive RT-PCR or real-time PCRs. V(1a) receptor mRNA levels (ratio against glyceraldehyde 3-phosphate dehydrogenase) were 0.378 +/- 0.143 (mean +/- SE) in preclinical CS (n = 5) and 0.630 +/- 0.072 in AIMAH (n = 4), which were significantly higher than those (0.046 +/- 0.012; n = 9) in control adrenals, whereas those in overt CS (0.143 +/- 0.048; n = 10) or aldosterone-producing adenomas (0.069 +/- 0.018; n = 12) were similar to control adrenals. Although ectopic expression of V(2) or V(3) receptor was detected in half of AIMAH cases, the absolute levels were low. Furthermore, V(1a) receptor mRNA levels in the adjacent adrenal glands (0.190 +/- 0.039, n = 9) of aldosterone-producing adenomas were higher than those in control adrenals and in the corresponding tumor portions (0.079 +/- 0.024). In contrast, there were no significant differences in AVP mRNA levels among these groups. These results suggest that eutopic V(1a) receptor overexpression is involved in the etiology of AIMAH and a subset of adrenal adenomas causing overt or preclinical Cushing's syndrome. Our results imply a possible association of V(1a) receptor expression with adrenal hyperplasia.
authors.affiliation: Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan. mune@cc.gifu-u.ac.jp
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Mune
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murase
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Yamakita
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukuda
authors.forename: Masanori
authors.initials: M
authors.lastname: Murayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suwa
authors.forename: Junko
authors.initials: J
authors.lastname: Hanafusa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Daido
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Keigo
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D000307:Adrenal Gland Diseases / Q000235:genetics / Q000378:metabolism*; D000311:Adrenal Glands / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000235:genetics; D003480:Cushing Syndrome / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone