Immunoreactive endothelin-1 and its receptors in human adrenal tissues.
To elucidate the pathophysiologic significance of endothelin-1 (ET-1) in adrenal and the mechanism for reduced responsiveness to exogenous ET-1 in aldosterone-producing adenoma (APA), we have investigated ET-1 receptors by radioligand binding assay (RBA) in human normal adrenal (NA), APA, idiopathic hyperaldosteronism (IHA), and pheochromocytoma (PHEO), immunoreactive (ir-) ET-1 content in NA, APA and PHEO by radioimmunoassay (RIA), and immunohistochemical staining of ET-1 with the peroxidase-anti-peroxidase (PAP) method in NA, APA, and PHEO. A single class of high-affinity binding sites for ET-1 was found in human NA and tumor tissues. Dissociation constant (Kd) values of ET-1 receptors were similar in NA, APA, and IHA, but maximal binding capacity (Bmax) of ET-1 receptors was lower in APA than in NA and IHA. Both Kd and Bmax in PHEO were higher than those in NA, APA, and IHA. Ir-ET-1 content in tumors of APA and PHEO were higher than in NA. Immunohistochemical staining was more intense in the tumor cells of APA and PHEO than in NA. These results suggest that the reduced response to exogenous ET-1 in APA could be related to downregulation of ET-1 receptors in the tumor. Increased ET-1 content and receptors may lead to hypersecretion of catecholamine in PHEO. ET-1 produced in normal and tumor adrenal tissues may regulate aldosterone and catecholamine secretion from adrenals in a paracrine/autocrine fashion.
Zeng
Z
Z
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Tang
X
X
Yang
D
D
Li
H
H
Zhang
R
R
Zeng
Q
Q
Li
M
M
Chen
J
J
Lu
Z
Z
Demura
H
H
Naruse
M
M
Shi
Y
Y
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism*; D015536:Down-Regulation; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D011863:Radioimmunoassay; D017466:Receptors, Endothelin / Q000378:metabolism*
D019332:Endothelin-1; D017466:Receptors, Endothelin