Expression and function of adrenomedullin and its receptors in Conn's adenoma cells.
Adrenomedullin (ADM) is a hypotensive peptide, that derives from the proteolytic cleavage of pro(p)ADM and acts through two subtypes of receptors, called L1-receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR may function as a calcitonin gene-related peptide or a selective ADM receptor depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of proteins, named receptor-activity modifying proteins (RAMPs). Reverse transcription (RT)-polymerase chain reaction (PCR) allowed the detection of pADM mRNA in dispersed cells of eight Conn's adenomas (aldosteronomas). These cells also expressed peptidyl-glycine alpha-amidating monooxigenase, the enzyme converting immature ADM to the mature form, and contained sizeable amounts of ADM-immunoreactivity as measured by radioimmunoassay. RT-PCR also demonstrated the presence in aldosteronoma cells of the specific mRNAs of L1-R, CRLR and RAMPs 1-3. ADM (10(-8) M) inhibited angiotensin-II (10(-9) M)-simulated aldosterone secretion from cultured aldosteronoma cells, without affecting basal production. ADM (10(-8) M) also enhanced basal proliferation rate of cultured cells, as estimated by the 5-bromo-2'-deoxyuridine immunocytochemical technique. Both effects of ADM were annulled by the ADM-receptor selective antagonist ADM22-52 (10(-7) M). In conclusion, our study provides evidence that aldosteronoma cells express both ADM and ADM22-52-sensitive receptors. These findings, coupled with the demonstration that ADM exerts an aldosterone antisecretagogue action and a proliferogenic effect on cultured aldosteronoma cells, make it likely that endogenous ADM system plays a potentially important role in the paracrine or autocrine functional control of Conn's adenomas.
Forneris
M
M
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, I-35121 Padua, Italy.
Gottardo
L
L
Albertin
G
G
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology; D053607:Adrenomedullin; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000473:pathology; D010455:Peptides / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D010455:Peptides; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D000804:Angiotensin II; D053607:Adrenomedullin; D000450:Aldosterone