Eutopic overexpression of vasopressin v1a receptor in adrenocorticotropin-independent macronodular adrenal hyperplasia.
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.
Mune
Tomoatsu
T
Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan. mune@cc.gifu-u.ac.jp
Murase
Hiroshi
H
Yamakita
Noriyoshi
N
Fukuda
Tetsuya
T
Murayama
Masanori
M
Miura
Atsushi
A
Suwa
Tetsuya
T
Hanafusa
Junko
J
Daido
Hisashi
H
Morita
Hiroyuki
H
Yasuda
Keigo
K
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*
D020033:Protein Isoforms; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone