Prohormones endorphins

In the anterior pituitary gland (see Hormones, anteriorpituitaryhormones), both adrenocorticotropic hormones (ACTH) and the endogenous opiate hormone, P-endorphin, are synthesized from a common prohormone (2) (see Opioids,endogenous). In the adrenal medulla, five to seven copies of another opiate hormone, methionine—enkephalin (Met-enkephalin), and one copy of leucine—enkephalin (Leu-enkephalin) are synthesized from each precursor molecule (3). 

The third prohormone from which opioid peptides are derived is pro-opiomelanocortin, which yields a number of nonopioid and opioid peptide products (O Donohue and Dorsa 1982). Of these products, beta-endorphin, an untriakontapeptide isolated from camel pituitary gland by Li and Chung (1976)) is thought to interact primarily with mu and delta receptors. 

Anterior pituitary hormones include growth hormone (GH), thyrotropin (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and adrenocorticotropin (ACTH). Another peptide, B-lipotropin (B-LPH), is derived from the same prohormone, proopiomelanocortin, as ACTH. B-LPH is secreted from the pituitary (along with ACTH), and is a precursor of the opioid peptide B-endorphin (see Chapter 31 Opioid Analgesics Antagonists). 

One of the highly characterized prohormones is the pro-opiomelanocortin (POMC) also known as proadrenocorticotropin and 31 K ACTH/endorphin. The POMC family consists of peptides which act as hormones (ACTH, LPH, MSH) and others which may serve as neurotransmitters or neuromodulators (endorphins). POMC is synthesized as a precursor molecule of about 285 amino acids and is processed differently in various regions of the pituitary. One gene is responsible for POMC expression. 

Proenkephalin-A contains six copies of Met-enkephalin and one of the Leu-analog. Some of the probable cleavage products (e.g., Met-enkephalin-Arg-Gly-Leu) occur as normal constituents of adrenal chromaffin cells. /3-Endorphin originates from a prohormone which is the common precursor of ACTH, a-, and /3-melanocyte-stimulating hormone and /3-endorphin (the prohormone also includes the /3-lipotropin sequence)/227 ... 

In addition to P-endorphin, P-LPH contains the amino acid sequence of another endogenous opioid, met-enkephalin. However, this peptide is not the product of P-LPH breakdown, but rather arises from a precursor molecule loiown as pro-enkephalin. Pro-enkephalin is widely distributed in neurons throughout the brain and spinal cord. Some pro-enkephalin is found in the pituitary gland, but most is localized in the catecholamine-synthesizing cells of the adrenal medulla and is co-released with epinephrine and norepinephrine. In the medulla, pro-enkephalin gives rise to met-enkephalin (Tyr-Gle-Gle-Phe-Met) and leu-enkephalin (Tyr-Gle-Gle-Phe-Leu) and to larger opioid peptides. A third family of endogenous opioid peptides is derived from prodynorphin, a prohormone stored primarily in the poste-... 

ACTH is derived from a large polypeptide precursor, proopiomelanocortin (POMC) that also includes in its amino acid sequence both MSH and the related opiate -lipotropin (y3-LPH), the latter giving rise to the biologically active )3-endorphin (Mains and Eipper, 1980). POMC, a 31 kDa polypeptide, is synthesized in the anterior and intermediate lobes of the pituitary gland, which is the most important source of this prohormone. Other notable sources of POMC synthesis in the brain include the amygdala and the arcuate nucleus of the hypothalamus (Watson and Akil, 1980 Civelli et al., 1982). In addition, the structure of the POMC molecule, the POMC gene and the mRNA sequence for POMC have been elucidated (Roberts... 

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