Role of Somatostatin Receptors in Normal and Tumoral Pituitary Corticotropic Cells

Normal and tumoral pituitary corticotropic cells express sst 2 and sst 5 , of which sst 5 is the predominantly expressed receptor subtype. Somatostatin (SS) inhibits pituitary adrenocorticotropin hormone (ACTH) secretion in vitro, but the sensitivity to SS is strongly regulated by glucocorticoids. In pathological conditions of a low endogenous cortisol level, i.e. in patients with adrenal insufficiency and in patients with Nelson’s syndrome, SS and sst 2 -preferring SS analogs (SSA), such as octreotide, are able to lower circulating ACTH and cortisol levels. On the other hand, sst 2 -preferring SSA seem not effective in lowering ACTH and cortisol levels in patients with untreated Cushing’s disease (CD), in which circulating cortisol levels are high. This is likely due to the downregulation of sst 2 receptors by glucocorticoids. sst 5 receptor expression is more resistant to the inhibitory effect of glucocorticoids. In recent years, novel sst subtype-selective and universal SSA have been developed. In particular, SSA with a high sst 5 binding affinity are potent inhibitors of ACTH secretion by pituitary corticotropic adenoma cells. This knowledge has Published online: September 10, 2010 Leo J. Hofland Department of Internal Medicine, Division of Endocrinology Room Ee530b, Dr. Molewaterplein 50 NL–3015 GE Rotterdam (The Netherlands) Tel. +31 10 703 4633, Fax +31 10 703 5430, E-Mail l.hofland @ erasmusmc.nl © 2010 S. Karger AG, Basel 0028–3835/10/0925–0011$26.00/0 Accessible online at: www.karger.com/nen D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 2/ 20 17 7 :1 2: 45 P M Hofland/Lamberts/Feelders Neuroendocrinology 2010;92(suppl 1):11–16 12 sst 5 , have been identified. On the basis of structural and pharmacological characteristics, two subclasses have been identified. To one class of sst, consisting of sst 2 , sst 3 and sst 5 , structural SS analogs (SSA), such as octreotide and lanreotide, bind with high affinity, whereas these SSA do not bind to the other class of sst, consisting of sst 1 and sst 4 ( table 1 ) [4] . Among the multiple physiological effects of SS is its potent inhibitory effect on pituitary hormone secretion [2, 3] . SS is considered as a physiological regulator of GH secretion. In vitro, the peptide inhibits the secretion of GH, prolactin (PRL), thyroid stimulating hormone (TSH), as well as adrenocorticotropin hormone (ACTH) by rat anterior pituitary cells, although its effects are strongly influenced by the respective physiological feedback hormones [5] . In human fetal pituitary cell cultures, SS inhibits the secretion of GH, TSH and PRL, whereas the release of ACTH and luteinizing hormone (LH) is only modestly influenced [6] . The effects of SS on normal and tumoral ACTH secretion are strongly regulated by glucocorticoids, representing the physiological feedback system [5] . Role of Somatostatin Receptors in Normal