More about Somatostatin and Somatostatin Analogues
Somatostatin
Somatostatin is a regulatory peptide. It was first isolated from the hypothalamus in 1973 by Paul Brazeau and identified as a hormone that inhibited secretion of growth hormone. Subsequently, somatostatin was found to be secreted by a broad range of tissues including other regions of the central nervous system, the gastrointestinal (GI) tract, the pancreas, ganglia, retina, vagus and sciatic nerves. It exists in two forms, with either 14 or 28 amino acids in a cyclic chain.
One of the main sites of secretion of somatostatin within the central nervous system is the hypothalamus. From here, it acts on receptors in the adjacent pituitary gland, exerting an inhibitory effect on the release of many pituitary hormones including growth hormone, thyrotropin, prolactin and corticotrophin. Its inhibitory effect on growth hormone and thus cell proliferation is perhaps most marked1.
The other major sites of somatostatin secretion are the pancreas and the GI tract, where it is released by epithelial cells and by neurones in the enteric nervous system.
Somatostatin inhibits the release of insulin and glucagon from the pancreas. It also exerts a general inhibitory effect on many other gut hormones including gastrin, gastric inhibitory peptide, cholecystokinin, secretin, vasoactive intestinal polypeptide and motilin. The net effect of somatostatin's inhibitory effect on gut hormones is to reduce gut exocrine secretions and thus digestion, decrease GI motility and decrease absorption of nutrients.
Somatostatin and its analogues have been shown to induce pain relief in a number of clinical contexts. In acromegaly, there is a widely reported reduction in joint pain2,3,4. Pain relief in gastrointestinal tumours, has also been reported5.
The mechanisms by which somatostatin exerts its analgesic effects are not clear, although circulating endogenous beta-endorphin levels were shown to increase in patients with advanced gastrointestinal cancer, following treatment with a somatostatin analogue5.
In addition somatostatin has an antiproliferative effect on some tumours where somatostatin receptors are present.
Somatostatin Analogues
The structures of the somatostatin analogues that have been tested in man differ from that of native somatostatin by the number and composition of their amino acids. These analogues have a marked anti-secretory action on GH, thyrotrophin and the peptide hormones of the gastro-enteropancreatic endocrine system, but with a higher selectivity for GH.
The duration of action of these analogues is markedly longer than that of the native peptide because of their high degree of resistance to enzymatic degradation.
References
1. Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999; 20: 157-198.
2. Giusti M, Gussoni G, Cuttica CM, Giordano G. Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly: six-month report on an Italian multicenter study. Italian Multicenter Slow Release Lanreotide Study Group. J Clin Endocrinol Metab 1996; 81: 2089-2097.
3. Giusti M, Ciccarelli E, Dallabonzana D, et al. Clinical results of long-term slow-release lanreotide treatment of acromegaly. Eur J Clin Invest 1997; 27: 277-284.
4. Colao A, Marzullo P, Vallone G, et al. Ultrasonographic evidence of joint thickening reversibility in acromegalic patients treated with lanreotide for 12 months. Clin Endocrinol 1999; 51: 611-618.
5. Befon S, Mystakidou K, Lyra M, Tubanakis N, Vlahos L. Continuous subcutaneous octreotide in gastrointestinal cancer patients: pain control and beta-endorphin levels. Anticancer Res 2000; 20: 4039-4046.
