Gene transcription of receptors for growth hormone-releasing peptide and somatostatin in human pituitary adenomas.
Growth hormone (GH)-releasing peptides (GHRP) or secretagogs (GHS) constitute a family of synthetic compounds with potent and specific GH releasing activity. The receptor (GHS-R) has recently been cloned even though the endogenous ligand remains to be identified. GHRPs act both at the hypothalamic and the pituitary level through mechanisms involving amplification of GH-releasing hormone activity and functional somatostatin antagonism. In the present study we examined the co-expression of messenger RNA (mRNA) for GHS-R and all 5 somatostatin receptor subtypes (sstr 1-5) in 28 human pituitary tumors by RT-PCR. GHS-R transcription was detected in 11 out of 12 somatotroph adenomas and in 2 out of 2 prolactinomas, whereas GHS-R expression was detected in only 2 out of 14 clinically nonfunctioning adenomas (NFPA), and no expression was seen in the only ACTH secreting adenoma. Almost all tumors expressed sstr 2 mRNA (n = 24), whereas only 1 tumor expressed sstr 4 mRNA. The expression of sstr 3 mRNA was inversely associated with GHS-R expression (P < 0.001), which could be attributed to a high prevalence of sstr 3 expression in NFPA. This study suggests that GHS-R expression is predominantly observed in somatotroph adenomas and much less so in NFPA. Moreover, the presence of a distinct pattern of somatostatin receptor subtype co-expression is suggested, which may provide a molecular basis for the complex interaction between GHRPs and somatostatin.
Medical Department M, Aarhus Kommunehospital, Aarhus University Hospital, Aarhus C, Denmark. stn@afdm.aau.dk
S
S
Nielsen
S
S
Mellemkjaer
L M
LM
Rasmussen
T
T
Ledet
J
J
Astrup
J
J
Weeke
J O
JO
Jørgensen
D000172:Acromegaly / Q000378:metabolism; D000236:Adenoma / Q000378:metabolism*; D003480:Cushing Syndrome / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism; D011446:Prospective Studies; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000235:genetics*; D014158:Transcription, Genetic
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D017481:Receptors, Somatostatin; C039542:somatocrinin receptor