What is POMC and Where is it Produced?
Proopiomelanocortin is the product of a single common gene. Structurally, it is a polypeptide chain comprising 265 amino acid residues.
Sites of Synthesis: POMC is produced in the anterior and intermediate lobes of the pituitary gland, as well as in the intestine and placenta.
Which Hormones are Derived from POMC?
Proteolytic processing of the POMC molecule yields several biologically active substances:
- Adrenocorticotropic hormone (ACTH).
- Melanocyte-stimulating hormone (MSH).
- $\beta$-endorphin and other peptides.
How is Synthesis Regulated?
The key regulator of POMC production is corticotropin-releasing hormone (CRH), a principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis.
Neurosecretory cells of the hypothalamus are activated by CNS inputs, primarily from the limbic system. CRH stimulates proopiomelanocortin-producing cells in the adenohypophysis.
Physiological Effects of POMC Derivatives
POMC cleavage products exert the following effects:
- Thermoregulation: ACTH, $\alpha$-, and $\gamma$-MSH act as endogenous antipyretics. They modulate the activity of neurons in the septal area and other brain regions that relay signals to the thermoregulatory center, preventing body temperature from exceeding 41–42 °C and protecting against lethal hyperthermia.
- Energy Homeostasis: POMC derivatives are a component of the leptin-melanocortin pathway, which regulates feeding behavior and energy balance.
- Central Nervous System Role: POMC derivatives include ACTH, $\alpha$-, and $\gamma$-melanocyte-stimulating hormones.
Clinical Significance
Addison's Disease (Primary Adrenal Insufficiency) In tubercular or autoimmune destruction of the adrenal cortex, corticosteroid synthesis declines. This leads to the loss of negative feedback and increased secretion of ACTH. Because ACTH and MSH share a common precursor (POMC), excess ACTH and co-released peptides stimulate melanocytes, resulting in characteristic hyperpigmentation of the skin and mucous membranes ("bronze skin"). Associated symptoms include hypotension, muscle weakness, hyponatremia, hypoglycemia, and stress intolerance.
Monogenic Obesity Mutations in the genes encoding proopiomelanocortin, melanocortin receptors, or leptin disrupt the appetite-regulation cascade, causing an extremely rare form of genetically determined obesity. The condition manifests in the first months of life and is characterized by hyperphagia, rapidly progressive morbid obesity by preschool age, and secondary hypogonadism.