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Proopiomelanocortin

 

 

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. 

 

 

It is  is synthesized in corticotrophs of the anterior pituitary from the precursor pre-pro-opiomelanocortin by the removal of a 26-amino-acid-long signal peptide sequence during translation.

 

 

POMC is part of the central melanocortin system.

 

 

Chromosome 2.

 

 

The POMC gene is expressed in both the anterior and intermediate lobes of the pituitary gland. 

 

 

POMC is cleaved and gives rise to multiple peptide hormones. 

 

 

Each of these peptides is packaged in large dense-core vesicles that are released from the cells by exocytosis in response to appropriate stimulation:

 

 

Hormones: α-MSH produced by neurons in the ventromedial nucleus has regulates appetite.

 

 

α-MSH secreted from the intermediate lobe of the pituitary regulates the movement of melanin produced from melanocytes in skin.

 

 

POMC neuron stimulation results in satiety and sexual behavior.

 

 

ACTH is a peptide hormone that regulates the secretion of glucocorticoids from the adrenal cortex.

 

 

β-Endorphin and enkephalins are endogenous opioid peptides with widespread actions in the brain.

 

 

This POMC gene encodes an amino acid polypeptide hormone precursor that undergoes extensive, 

 

post-translational processing via cleavage by enzymes known as prohormone convertases. 

 

 

The encoded protein POMC is synthesized mainly in corticotroph cells of the anterior pituitary.

 

 

There are  four cleavage sites for POMC: adrenocorticotrophin (ACTH), essential for normal steroidogenesis and the maintenance of normal adrenal function, and β-lipotropin are the major end-products. 

 

 

There are at least eight potential cleavage sites within the polypeptide precursor and, processing may yield as many as ten biologically active peptides involved in diverse cellular functions. 

 

 

Proteases that recognize these cleavage sites are tissue-specific: the hypothalamus, placenta, and epithelium, cleavage sites may be used, giving rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation. 

 

 

It is synthesized by:

 

 

Corticotrope cells of the anterior pituitary gland

 

 

Melanotrope cells of the intermediate lobe of the pituitary gland

 

 

Neurons in the arcuate nucleus of the hypothalamus

 

 

Smaller populations of neurons in the dorsomedial hypothalamus and brainstem

 

 

The levels of proopiomelanocortin are regulated indirectly  by the photoperiod: the hours of light during a day and it changes across the seasons. 

 

 

Also its regulation depends on the pathway of thyroid hormones that is regulated directly by the photoperiod. 

 

 

POMC is the source of several important biologically active substances, and can be cleaved enzymatically into the following peptides:

 

 

N-Terminal Peptide of Proopiomelanocortin

 

 

Melanocyte-Stimulating Hormone

 

 

Corticotropin (Adrenocorticotropic Hormone, or ACTH)

 

 

β-Lipotropin (β-LPH)

 

 

Gamma Lipotropin (γ-LPH)

 

 

β-Endorphin

 

 

Enkephalin

 

 

Mutations in this gene have been associated with early onset obesity, adrenal insufficiency, and red hair pigmentation.

 

 

The combination of bupropion and naltrexone acts via hypothalamic POMC neurons to decrease appetite for weight control.

 

 

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