High density of somatostatin receptors in pituitary tumors from acromegalic patients.
Using a SRIH receptor-binding assay previously developed for rat pituitary tissue, we measured SRIH-binding sites in human pituitary adenomas obtained from five acromegalic patients. Saturable and high affinity-binding sites for SRIH were found, with respective dissociation constants (Kd) of 0.57, 1.48, 1.04, 0.24, and 1.04 nM for the different adenomas, which is comparable with the Kd of 0.95 nM for SRIH in normal rat pituitary. In adenomas of most patients, however, the number of sites was much higher than in rat pituitary (100 fmol/mg protein), being, respectively, 757, 800, 441, 103, and 1058 fmol/mg protein. The pharmacological characteristics of these sites were similar in both species, [Des-Trp8]SRIH being inactive but the stable SRIH analog SMS 201-995 [H-(D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Thr(ol)] being slightly more potent than SRIH. This is the first description of specific SRIH-binding sites in human pituitary tissue and in particular in human pituitary adenomas. These results suggest that the development of GH-secreting pituitary adenomas is not due to the absence of SRIH receptors or to a decrease in their affinity for SRIH. The large number of sites with high affinity for SMS 201-995 suggests that the use of SRIH analogs could be of potential benefit in reducing GH levels in patients with acromegaly.
D000172:Acromegaly / Q000209:etiology / Q000378:metabolism*; D000236:Adenoma / Q000150:complications / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism*; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000302:isolation & purification*; D017481:Receptors, Somatostatin
D011956:Receptors, Cell Surface; D017481:Receptors, Somatostatin