The sequence of somatostatin-14 (SS1) has been strongly preserved throughout the evolution of vertebrates from agnathans to mammals. In Acipenseridae (sturgeons), two isoforms of somatostatin have been characterized to date: somatostatin-14 has been identified from the gastrointestinal tract of the pallid sturgeon Scaphirhynchus albus and [Pro(2)]somatostatin-14 has been identified from the pituitary of the Russian sturgeon Acipenser gueldenstaedti. In the present study, we report the cloning of two distinct somatostatin cDNAs from the brain of the sturgeon Acipenser transmontanus. One of the cDNAs encodes a 116-amino acid protein (PSS1) that contains the SS1 sequence at its C-terminal extremity and, thus, is clearly orthologous to other vertebrate PSS1. The other cDNA encodes a 111-amino acid protein that contains the somatostatin variant [Pro(2)]somatostatin-14 at its C-terminal extremity. This second precursor exhibits more than 67% identity with the recently characterized lungfish PSS2 and goldfish PSS2. Reverse transcriptase-polymerase chain reaction analysis revealed that PSS1 is expressed in the central nervous system, the pancreas and the gut, whereas PSS2 is found in the central nervous system but not in the digestive system. In situ hybridization histochemistry showed that the PSS1 and PSS2 genes are differently expressed in numerous regions of the sturgeon brain. Interestingly, PSS1 and PSS2 mRNAs are present in the hypothalamus suggesting that, in sturgeon, both SS1 and SS2 may play hypophysiotropic functions. The PSS2 mRNA but not the PSS1 mRNA was found in the intermediate lobe of the pituitary. The present data demonstrate that two somatostatin genes are expressed in the sturgeon brain: one precursor generates somatostatin-14 and the other one gives rise to a [Pro(2)]somatostatin-14 variant, which is orthologous to goldfish, lungfish, and frog SS2.