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Although the existence of two somatostatin variants (SS1 and SS2) has now been demonstrated in the brain of mammals, amphibians, and fish, only one isoform of somatostatin (SS1) has been characterized to date in the brain of birds. Here we report cloning of the cDNA encoding a 101-amino-acid protein (PSS2) that encompasses the somatostatin variant [Pro2]somatostatin-14 (SS2) at its C-terminus. Sequence analysis indicated that chicken PSS2 is more closely related to fish PSS2 than to mammalian cortistatin precursors. Northern blot analysis showed that the chicken PSS1 gene is expressed in the central nervous system (CNS) and in the pancreas, whereas the PSS2 gene is expressed only in the CNS and not in peripheral organs. In situ hybridization histochemistry revealed that, in the chicken brain, PSS1 mRNA is more widely distributed than PSS2 mRNA. In particular, PSS1 mRNA expression was found in the hippocampus, the hyperstriatum, the preoptic area, the ventricular hypothalamic nuclei, the optic tectum, and several nuclei of the mesencephalon and rhombencephalon. In contrast, the distribution of PSS2 mRNA was restricted to a few regions of the brain, including the paraolfactory lobe, the paleostriatum, and some nuclei of the mesencephalon and rhombencephalon. The fact that the PSS1 and PSS2 genes are differently expressed in the brain and in peripheral organs indicates that, in chicken, the two somatostatin variants likely exert distinct functions. In particular, the observation that PSS1 mRNA, but not PSS2 mRNA, occurs in the preoptic area and in the ventral hypothalamic nuclei suggests that, of the two somatostatin isoforms, only SS1 acts as a hypophysiotropic factor. J. Comp. Neurol. 461:441–451, 2003. © 2003 Wiley-Liss, Inc.

The occurrence of two somatostatin precursors, PSS1 and PSS2, yielding S-14 (SS1) and the variant [Pro2, Met13]S-14 (SS2), has been recently reported in the frog Rana ridibunda. The evolutionary significance of frog PSS2 is unclear because its sequence exhibits very little similarity with other known vertebrate somatostatin precursors. In the present study, we report on the characterization of two somatostatin precursor cDNAs from the brain of the African lungfish Protopterus annectens. One of the cDNAs encodes a 115-amino-acid protein that contains the SS1 sequence at its C-terminal extremity and thus is clearly homologous to PSS1. Comparison with other vertebrate PSS1 showed that lungfish PSS1 is more closely related to PSS1 from tetrapods than to PSS1 from fish. The other cDNA encodes a 109-amino-acid protein that contains a somatostatin variant [Pro2]S-14 at its C-terminal extremity. Sequence analysis of this second precursor indicated that it is the lungfish counterpart of frog PSS2. Northern blot analysis showed that lungfish PSS1 mRNA is widely distributed in the central nervous system and in peripheral organs, including the pancreas and gastrointestinal tract. In contrast, PSS2 mRNA was primarily found in the central nervous system but not in the pancreas or gut. In situ hybridization studies showed that the two genes are differentially expressed in various regions of the lungfish brain. The present data indicate that the PSS2 gene, initially discovered in frog, appeared early in vertebrate evolution, before the emergence of the tetrapod lineage. The recent isolation of a [Pro2]S-14 variant in the sturgeon, whose sequence is identical to that of lungfish SS2, suggests that the PSS2 gene may actually be present in the genome of all Osteichthyii.