2004 Volume 51 Issue 2 Pages 227-236
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 μg 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.