Linked Life Data

14671214

Source:http://linkedlifedata.com/resource/pubmed/id/14671214

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-12-12
pubmed:abstractText
The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that includes five seven-transmembrane G protein-coupled receptors and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short-loop feedback within the pituitary. ACTH-secreting adenomas are characterized by resistance to glucocorticoid feedback, and they may have dysregulated ACTH feedback. We therefore investigated the ACTH-R in normal and adenomatous human pituitary tissue. We report here the identification of ACTH-R mRNA in the human pituitary gland, which was confirmed by direct sequencing. We studied the expression of the ACTH-R in 23 normal pituitary specimens and 53 pituitary adenomas (22 ACTH-secreting, nine GH-secreting, eight prolactin-secreting, one TSH-secreting, one FSH-secreting, 10 nonfunctioning, and two silent corticotroph adenomas), using the sensitive technique of real-time quantitative PCR. Contamination of ACTH-secreting adenomas and nonfunctioning pituitary adenomas with nonadenomatous tissue was excluded by lack of Pit-1 expression. ACTH-R mRNA was detected in all normal pituitary specimens, and in situ hybridization colocalized expression to ACTH staining cells only. However, ACTH-R mRNA levels were undetectable in 16 of 22 ACTH-secreting tumors and in both silent corticotroph tumors. Diagnostic preoperative plasma ACTH levels were significantly lower in the ACTH-R positive ACTH-secreting tumors, compared with those who were ACTH-R negative (P = 0.0006). Direct sequencing of the coding region of the ACTH-R in cDNA from three ACTH-secreting tumors positively expressing the receptor showed no mutations, as did sequencing of genomic DNA in three receptor negative ACTH-secreting tumors and the two silent corticotrophs. These results provide further evidence compatible with an ACTH feedback loop in the pituitary and suggest that loss of expression of the ACTH-R in corticotroph adenomas of patients with Cushing's disease may play a role in the resistance to feedback of the pituitary-adrenal axis seen in these patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6080-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14671214-Adenoma, pubmed-meshheading:14671214-Adolescent, pubmed-meshheading:14671214-Adrenocorticotropic Hormone, pubmed-meshheading:14671214-Adult, pubmed-meshheading:14671214-Aged, pubmed-meshheading:14671214-Child, pubmed-meshheading:14671214-DNA, Complementary, pubmed-meshheading:14671214-Female, pubmed-meshheading:14671214-Humans, pubmed-meshheading:14671214-Immunohistochemistry, pubmed-meshheading:14671214-In Situ Hybridization, pubmed-meshheading:14671214-Male, pubmed-meshheading:14671214-Middle Aged, pubmed-meshheading:14671214-Pituitary Gland, pubmed-meshheading:14671214-Pituitary Neoplasms, pubmed-meshheading:14671214-Polymerase Chain Reaction, pubmed-meshheading:14671214-Pro-Opiomelanocortin, pubmed-meshheading:14671214-RNA, Messenger, pubmed-meshheading:14671214-Receptors, Corticotropin, pubmed-meshheading:14671214-Tissue Distribution
pubmed:year
2003
pubmed:articleTitle
Identification of adrenocorticotropin receptor messenger ribonucleic acid in the human pituitary and its loss of expression in pituitary adenomas.
pubmed:affiliation
Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't