Somatostatin (SRIF) receptor subtype 2 and 5 gene expression in growth hormone-secreting pituitary adenomas: the relationship with endogenous srif activity and response to octreotide.
To investigate the potential pathophysiologic role of human SRIF receptor gene expression in GH-secreting adenomas in acromegalic patients, we studied the relationship between the SRIF receptor gene expression, endogenous SRIF activity and exogenous response to octreotide in 16 acromagalic patients. Hypothalamic somatostatinergic activity (HSA) was assessed by glucose-induced suppression of TRH-stimulated TSH secretion. As an indicator of somatotrope sensitivity to HSA, glucose-induced suppression of TRH-stimulated GH secretion was determined. For the acute octreotide response, a 100 microg bolus of octreotide was injected intravenously and GH was measured hourly for 6 hr. Pituitary tumor SRIF receptor subtype 2 and 5 (sst2 and sst5) mRNA levels were measured by real-time RT-PCR. Gsp oncogene was also detected by direct PCR sequencing. Sst2 and sst5 mRNA levels were detected in all tumors. Sst2 mRNA levels positively correlated with that of sst5. Sst2 and sst5 mRNA levels did not show any correlation with basal GH values (nadir or peak). Expression of sst2, but not sst5, showed a positive correlation with the GH response to HSA, while the octreotide response positively correlated with the sum of sst2 and sst5 mRNA levels. Individuals with gsp-positive tumors were more responsive to octreotide than those with gsp-negative tumors but sst2 and sst5 mRNA levels did not differ between these two groups. These results suggest common transcriptional and/or post-transcriptonal regulatory mechanisms for these SRIF receptor subtypes within GH-secreting pituitary adenomas. The functional observations suggest that the degree (or level) of sst2 and sst5 expression is critical for the ultimate GH response of somatotropinomas to endogenous SRIF tone and exogenous SRIF analogue therapy. However, sst2 and sst5 mRNA levels are not the only factors mediating the response to SRIF.
Park
Cheolyoung
C
Department of Internal Medicine, College of Medicine, Hallym University, Kyunggi, Korea.
Yang
Inmyung
I
Woo
Jeongtaek
J
Kim
Sungwoon
S
Kim
Jinwoo
J
Kim
Youngseol
Y
Sohn
Sookjin
S
Kim
Eunhee
E
Lee
Mina
M
Park
Heesoon
H
Jung
Jeechang
J
Park
Seungjoon
S
D000172:Acromegaly / Q000188:drug therapy; D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism*; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D015282:Octreotide