title: Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome.
abstract: OBJECTIVE
  Aberrant adrenal expression of various hormone receptors has been identified in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing cortisol hypersecretion regulated by hormones other than ACTH. We aimed to determine aberrant expression of multiple hormone receptors in vivo and in vitro in adrenal tissue of a patient with AIMAH.
  
  
  METHODS
  The design of the study includes clinical case description, and biochemical and immunohistochemical analysis to demonstrate aberrant expression of multiple hormone receptors in AIMAH.
  
  
  METHODS
  The subject of the study is a male diagnosed with Cushing's syndrome because of AIMAH. Directly after laparoscopic removal of the adrenals, adrenal tissue was incubated with and without test substances (ACTH, forskolin, arginine vasopressin (AVP), desmopressin, epinephrine, norepinephrine, purified human chorionic gonadotropin (hCG), metoclopramide and the combinations of AVP with ACTH, epinephrine and metoclopramide). LH/hCG-receptor (hCG-R) immunohistochemistry and RT-PCR analyses were performed to demonstrate aberrant expression of LH/hCG-R and V(1-3)-AVPR.
  
  
  RESULTS
  AIMAH was characterized by in vivo cortisol responsiveness to AVP and in vitro cortisol responses to AVP, hCG, epinephrine, and norepinephrine suggesting aberrant adrenal expression of the receptors for AVP (the V(1-3)-AVPRs), catecholamines (the beta-AR), and LH (the LH/hCG-R). Incubation with combinations of AVP and ACTH and of AVP with epinephrine induced a stronger cortisol response compared with incubation with the individual agents. Moreover, we demonstrated adrenal V(1-3)-AVPR and LH/hCG-R expression.
  
  
  CONCLUSIONS
  AIMAH tissue may simultaneously express multiple aberrant hormone receptors, and individual ligands may potentiate each other regarding cell proliferation and cortisol production.
authors.affiliation: Department of Endocrinology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. j.w.b.de.groot@int.umcg.nl
authors.forename: J W B
authors.initials: JW
authors.lastname: de Groot
authors.forename: T P
authors.initials: TP
authors.lastname: Links
authors.forename: A P N
authors.initials: AP
authors.lastname: Themmen
authors.forename: L H
authors.initials: LH
authors.lastname: Looijenga
authors.forename: R R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: P M
authors.initials: PM
authors.lastname: van Koetsveld
authors.forename: J
authors.initials: J
authors.lastname: Hofland
authors.forename: G
authors.initials: G
authors.lastname: van den Berg
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
mesh_terms: D000307:Adrenal Gland Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D001127:Arginine Vasopressin / Q000378:metabolism; D003480:Cushing Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006965:Hyperplasia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011974:Receptors, LH / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011974:Receptors, LH; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D006854:Hydrocortisone