Introduction More than 20 yr ago, in an elegant series of pulsechase studies, Steiner and Oyer (1) demonstrated that insulin is synthesized in pancreatic islet cells as part of a larger molecule, proinsulin. Since that time, the concept that bioactive peptides are derived from larger precursors has become firmly established (2–4). Over the same period, the definitive structures of the majority of precursors of biologically active peptides have been fully characterized, both by classical protein sequence studies and more recently by recombinant DNA techniques (for reviews see Refs. 4–6). To yield biologically active products, precursors commonly undergo a series of highly organized posttranslational events, including selective proteolytic cleavage and other enzymatic modifications (e.g., phosphorylation, α-amidation, acetylation) which take place within specific membrane-bounded compartments. A number of precursor polypeptides contain within their structure amino acid sequences which have quite diverse bio...

Proopiomelanocortin Processing in the Pituitary, Central Nervous System, and Peripheral Tissues

Proopiomelanocortin (POMC) is the polypeptide precursor of ACTH. First discovered in anterior pituitary corticotroph cells, it has more recently been revealed to have many other physiological aspects. The fine molecular mechanisms of ACTH biosynthesis show that ACTH is but one piece of a puzzle which contains many other peptides. Present in various tissues, among which are pituitary, hypothalamus, central nervous system and skin, POMC undergoes extensive post-translational processing. This processing is tissue-specific and generates, depending on the case, various sets of peptides involved in completely diverse biological functions. POMC expressed in corticotroph cells of the pituitary is necessary for adrenal function. Recent developments have shown that POMC-expressing neurons in the brain play a major role in the control of pain and energy homeostasis. Local production of POMC-derived peptides in skin may influence melanogenesis. A still unknown function in the placenta is likely. POMC has become a paradigmatic polypeptide precursor model illustrating the variable roles of a single gene and its various products in different localities.

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Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

Characterization of rat spinal cord receptors to FLFQPQRFamide, a mammalian morphine modulating peptide: a binding study.

The content of pro-opiomelanocortin (POMC) mRNA was determined in the hypothalamus, as well as in the anterior and intermediate lobes of the pituitary gland of the alcohol-preferring AA and alcohol-avoiding ANA rats under basal conditions. In addition the content of beta-endorphin-like immunoreactivity (beta-EPLIR) was measured in nine brain regions, the anterior and intermediate lobes of the pituitary gland and the serum. The content of beta-EPLIR was significantly higher in the septum and significantly lower in the amygdala, and periaqueductal gray matter of the AA rats, while there was no significant difference between the AA and ANA rats in the arcuate nucleus plus median eminence, nucleus accumbens, caudate, hippocampus, and cortex. HPLC analysis indicated no significant differences in the relative proportions of non-acetyl and acetyl forms of beta-endorphin peptides in the hypothalamus, distinct brain regions, and anterior and neurointermediate lobes of the pituitary gland, between the AA and ANA rats. The content of POMC mRNA but not of beta-EPLIR was significantly higher in the hypothalamus and neurointermediate lobe of the AA rats, while the content of both beta-EPLIR and POMC mRNA were significantly higher in the anterior pituitary of the AA than of the ANA rats. Thus, there are genetically determined differences in the pituitary and brain beta-endorphin system between the AA and ANA rats, which may be important in controlling the differences in the voluntary ethanol consumption exhibited by these animals.

Differences in the brain and pituitary beta-endorphin system between the alcohol-preferring AA and alcohol-avoiding ANA rats.

Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissue...

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POMC: The Physiological Power of Hormone Processing.

Polyadenylated RNA isolated from porcine pituitary neurointermediate lobes was used to construct a cDNA library The library was screened with a rat genomic DNA fragment specific for pro-opiomelanocortin sequences Two positive clones, pJA-19 and pJA-20, containing respectively 850 bp and 550 bp were characterized Sequence analysis of the cDNA inserts revealed the complete structure of the porcine pro-opiomelanocortin mRNA This mRNA would include 129 5'-untranslated nucleotides, 801 nucleotides coding for the 267 amino acids precursor and 162 3'-untranslated nucleotides Comparison with pro-opiomelanocortin mRNA sequences from other species shows regions of high homology not only in the coding sequences but also in the 5'untranslated region where the first 50 nucleotides are over 80% purines

Claire Barbeau

Papers

Complete structure of the porcine pro-opiomelanocortin mRNA derived from the nucleotide sequence of doned cDNA