preprohormoner

A preprohormone is a molecular precursor to a peptide hormone, produced in secretory cells such as endocrine or neuroendocrine cells. Many peptide hormones are synthesized as preprohormones that undergo multiple processing steps before becoming active.

A preprohormone contains an N-terminal signal peptide, or presequence, which directs the polypeptide to the secretory pathway and into the endoplasmic reticulum. The signal peptide is cleaved within the ER, yielding a prohormone. The prohormone often includes extra segments that assist in proper folding and trafficking and are themselves removed during maturation.

During processing, specific proteolytic enzymes, including prohormone convertases (such as PC1/3 and PC2 in many endocrine tissues) and carboxypeptidases, cleave the prohormone at defined sites to generate the mature hormone. Additional post-translational modifications, such as disulfide bond formation and glycosylation, may occur. The mature hormone is then packaged into secretory granules and released in response to physiological stimuli.

Examples illustrate the pathway: preproinsulin is translated with a signal peptide, which is removed to form proinsulin; further processing yields mature insulin and C-peptide. Other instances include proglucagon, proopiomelanocortin, and various neuropeptide precursors that give rise to multiple active peptides.

The preprohormone framework provides a coordinated mechanism for synthesizing, folding, trafficking, and regulated secretion of peptide hormones. Misprocessing of preprohormones can lead to ineffective hormone production or disease states, highlighting the importance of precise proteolytic processing in hormone biology.