This gene encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. There are eight potential cleavage sites within the polypeptide precursor and, depending on tissue type and the available convertases, processing may yield as many as ten biologically active peptides involved in diverse cellular functions. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary where four cleavage sites are used; adrenocorticotrophin, essential for normal steroidogenesis and the maintenance of normal adrenal weight, and lipotropin beta are the major end products. In other tissues, including the hypothalamus, placenta, and epithelium, all cleavage sites may be used, giving rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation. These include several distinct melanotropins, lipotropins, and endorphins that are contained within the adrenocorticotrophin and beta-lipotropin peptides. Mutations in this gene have been associated with early onset obesity, adrenal insufficiency, and red hair pigmentation. Alternatively spliced transcript variants encoding the same protein have been described.
Although the N-terminal 5 amino acids of beta-endorphin are identical to the sequence of Met-enkephalin, it is not generally thought that beta-endorphin is converted into Met-enkephalin. Instead, Met-enkephalin is produced from its own precursor, proenkephalin.
The production of beta-MSH occurs in humans but not in mice or rats due to the absence of the enzymatic processing site in the rodent POMC.
Each of these peptides is packaged in large dense-core vesicles that are released from the cells by exocytosis in response to appropriate stimulation.
α-MSH produced by neurons in the arcuate nucleus has important roles in the regulation of appetite and sexual behavior, while α-MSH secreted from the intermediate lobe of the pituitary regulates the production of melanin.
ACTH is a peptide hormone that regulates the secretion of glucocorticoids from the adrenal cortex.
β-endorphin and met-enkephalin are endogenous opioid peptides with widespread actions in the brain.
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