Presence of somatostatin receptors negatively coupled to adenylate cyclase in ectopic growth hormone-releasing hormone- and alpha-subunit-secreting tumors from acromegalic patients responsive to octreotide.
The functional study of SRIH receptors was performed in ectopic GHRH-secreting tumors from two patients with acromegaly; patient 1 presented with multiple endocrine neoplasia type 1 with GHRH- and insulin-secreting pancreatic tumors, and patient 2 presented with a multihormone-secreting carcinoid tumor (including GHRH and alpha-subunit secretion, as demonstrated by clinical and immunohistochemical studies). In both cases, plasma GH levels were responsive to octreotide. In patient 2, plasma GHRH and alpha-subunit levels were responsive to octreotide. In vitro perifusion studies of a tumor fragment from patient 1 also showed inhibition of GHRH secretion by SRIH. A high density of specific SRIH-binding sites was visualized by autoradiography in GHRH tumors from both patients. SRIH specific binding was much higher in the GHRH tumors (6.6-8.4 fmol/surface unit) than in the insulinoma (1.9 fmol/surface unit). The binding inhibition constant (IC50) was in the nanomolar range (0.9-3 nmol/L) in the GHRH tumors. SRIH-14 inhibited forskolin-stimulated adenylate cyclase in the GHRH tumors from both patients, but not in the insulinoma. The functional SRIH receptors negatively coupled to adenylate cyclase present in ectopic GHRH-secreting tumors mediate the inhibitory effect of octreotide on GHRH secretion and on previously underrecognized ectopic alpha-subunit secretion from carcinoid tumors.
Bertherat
J
J
Peptide Biology Laboratory, Salk Institute, La Jolla, California 92186-5800.
Turpin
G
G
Rauch
C
C
Li
J Y
JY
Epelbaum
J
J
Sassolas
G
G
Schaison
G
G
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D002276:Carcinoid Tumor / Q000737:chemistry / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007340:Insulinoma / Q000737:chemistry / Q000378:metabolism; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000737:chemistry* / Q000378:metabolism; D015282:Octreotide / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000032:analysis* / Q000378:metabolism*
D017481:Receptors, Somatostatin; D005576:Colforsin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000262:Adenylyl Cyclases; D015282:Octreotide