preprosomatostatin

Preprosomatostatin is the initial translation product of the SST gene and serves as the precursor to somatostatin, a regulatory neuropeptide with inhibitory effects in endocrine and nervous system signaling. The prepropeptide contains an N-terminal signal sequence that directs the molecule to the secretory pathway.

After the signal peptide is removed, the remaining prohormone, prosomatostatin, undergoes proteolytic processing by prohormone convertases to generate the mature somatostatin peptides, primarily somatostatin-14 and somatostatin-28, along with additional intermediate fragments that are typically degraded. The mature peptides are packaged into secretory vesicles and released in response to physiological stimuli.

Expression of preprosomatostatin occurs in several tissues, notably hypothalamic neurons, pancreatic D cells, and various enteroendocrine and central nervous system populations. The two principal active forms, SST-14 and SST-28, differ in length and distribution, contributing to the peptide’s diverse regulatory roles.

Functionally, somatostatin acts as an inhibitory regulator of endocrine and exocrine secretion and as a neurotransmitter and neuromodulator in the brain. It suppresses growth hormone release from the pituitary and can reduce secretion of insulin, glucagon, GI hormones, and other peptides, as well as modulating neural activity.

Clinical relevance includes the observation that altered expression or processing of preprosomatostatin can affect somatostatin levels and physiology. Synthetic somatostatin analogs are widely used therapeutically to treat conditions such as acromegaly and certain neuroendocrine tumors, illustrating the clinical importance of the somatostatin system that originates from this precursor.