preprosomatostatiinista

Preprosomatostatin is the precursor protein that gives rise to the active peptide hormone somatostatin, a key regulator of endocrine and exocrine secretion. It is encoded by the SST gene in humans and other mammals. The primary transcript is translated into a preproprotein that contains a signal peptide, the globulin domain and the neuropeptide region. The signal peptide directs the nascent polypeptide into the endoplasmic reticulum where it is cleaved, producing prosomatostatin. Subsequent proteolytic processing, primarily by prohormone convertases and carboxypeptidases, generates the mature somatostatin-14 or somatostatin-28 peptides that are stored in secretory granules.

Somatostatin acts as a broad-spectrum inhibitor of hormone release, affecting growth hormone, insulin, glucagon, gastrin, and many other peptides. It also modulates neuronal signaling and immune responses by binding to five distinct G‑protein coupled somatostatin receptors (SSTR1–5). The preprosomatostatin gene is regulated by neural activity, stress, and metabolic signals, ensuring that somatostatin levels adapt quickly to physiological demands.

In addition to its endocrine functions, preprosomatostatin is involved in neuropeptide trafficking and the assembly of secretory granules. Genetic studies in knockout mice reveal deficits in growth hormone secretion, altered glucose homeostasis, and impaired neuroendocrine signaling. Clinically, alterations in preprosomatostatin processing are implicated in conditions such as acromegaly, neuroendocrine tumors, and certain pituitary disorders. Synthetic analogues of the mature peptides, such as octreotide and lanreotide, are used therapeutically to inhibit hormone overproduction and to treat gastroenteropancreatic neuroendocrine tumors.

Overall, preprosomatostatin represents a critical developmental and functional precursor in the regulation of endocrine and neuronal physiology, with its proper processing essential for maintaining metabolic and hormonal balance.