Proopiomelanocortin

Fig. 1. Schematic drawing of precursors for selected brain oligopeptides. Shaded areas represent the location of sequences of active peptide products which are normally cleaved by trypsin-like enzymes acting on double-basic amino acid residues. Precursors are not necessarily drawn to scale, (a) CRF precursor (b) proopiomelanocortin (POMC) (c) P-protachykinin (d) proenkephalin A (e) CGRP precursor (f) preprodynorphin, ie, preproenkephalin B. Terms are...

Proopiomelanocortin (POMC) is the precursor peptide of hormones and neuropeptides expressed in the pituitary and the hypothalamus (adrenocorticotropic hormone (ACTH), lipotropin, a-melanocyte-stimulating hormone (aMSH), yMSH, 3-endorphin, and others). The main clinical consequences of POMC deficiency are adrenal insufficiency (due to absence of ACTH), red hair pigmentation (due to absence of MSH) and severe early-onset obesity (due to the lack of aMSH). 

Young E, Bronstein D, Akil H. Proopiomelanocortin biosynthesis, processing and secretion functional implications. In Opioids I. Handbook of Experimental Pharmacology, Vol. 104 (Herz A, ed). Springer, Heidelberg, 1993 393-721. 

FIGURE 18-7 Processing of the proopiomelanocortin (POMC) precursor proceeds in an ordered, stepwise fashion. Cleavage of the POMC precursor occurs at seven sites, with some of the reactions being tissue-specific. The circled numbers indicate the temporal order of cleavage in tissues where these proteolytic events occur. ACTH, adrenocorticotropic hormone CLIP, corticotropin-like intermediate lobe peptide JP, joining peptide LPH, lipotropin MSH, melanocyte-stimulating hormone PC, prohormone convertase. 

Laurent, V., Jaubert-Miazza, L., Desjardins, R., Day, R. and Lindberg, I. Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice. Endocrinology 145 519-528, 2004. 

Schauer, E. et al., Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes, J. Clin. Invest. 93, 2258-2262,1994. 

The classic endogenous opioid peptides are derived from one of three families of precursors proopiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. Many active opioid peptides are derived from these three, but the best known are )S-endorphin, enkephalin, and dynorphin. POMC is produced by nuclei in the hypothalamus and medulla (Khachaturian et al. 1985 Watson et al. 1978 Bloom et al. 1978). Enkephalin and dynorphin neurons are distributed to all levels of the central nervous system (Hokfelt et al. 1977 Khachaturian et al. 1983 Sar et al. 1978 Khachaturian et al. 1985). 

The peptide, melatonin, has been implicated in autism. Excess melatonin is thought to decrease learning, memory, attention, emotionality, motivation and pain responses (reviewed Chamberlain Herman, 1990)—all behaviours that are abnormal in autism. Melatonin, released from the pineal gland, is implicated in controlling serotonin and POMC (proopiomelanocortin) peptides, such as beta-endorphin, and an elevation may contribute to, or cause, the serotonin and opioid abnormalities (Chamberlain Herman, 1990). 

Lightman SL, Young WS 3rd (1988) Corticotrophin-releasing factor, vasopressin and proopiomelanocortin mRNA responses to stress and opiates in the rat. J Physiol 403 511-523 Lolait SJ, O Carroll AM, Mahan LC, Felder CC, Button D, Yoimg III WS, et al (1995) Extra-pituitary expression of the rat Vlb vasopressin receptor gene. Proc Natl Acad Sci USA 92 6783-6787... 

Kaye, W.H., Berrettlnl, W.H., Gwlrtsman, H.E., Chretien, M., Gold, P.W., George, D.T., Jlmerson, D.C., and Ebert, M.H. (1987a) Reduced cerebrospinal fluid levels of Immunoreactive proopiomelanocortin related peptides (Including beta-endorphin) in anorexia nervosa. Life Sci 41 2147-2155. 

Herman, B.H. (1990) A possible role of proopiomelanocortin peptides in self-injurious behavior. Prog Neuropsychopharmacol Biol Psychiatry 14 S109—S139. 

Proopiomelanocortin ( ) Mammary tumor virus Pituitary Mammary gland Epidermis Fat body... 

Several studies have indicated that HA in addition to other hypothalamic neurotransmitters [14] are involved in the neuroendocrine regulation of the proopiomelanocortin (POMC)-derived... 

Note Three distinct families of peptides have been identified the enkephalins, the endorphins, and the dynorphins. Each family is derived from a distinct precursor polypeptide and has a characteristic anatomical distribution. These precursors are now designated as proenkephalin (also proenkephalin A), proopiomelanocortin (POMP), and prodynorphin (also proenkephalin). 

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). 

In rat pars intermedia cells, the rate of secretion of the proopiomelanocortin-derived peptides (a-MSH being the major secretory product) (3, 85) was so far known to result from a balance between the stimulatory effect of B-adrenergic agents and the inhibitory influence of dopaminergic substances (14, 41, 86-89). The present data clearly demonstrate that in addition to B-adrenergic agents, a second substance, namely CRF, could well be involved as physiological stimulator of the activity of pars intermedia cells. 

Figure 10.3. Identification of open reading frames with ORF Finder. The nucleotide sequence encoding human proopiomelanocortin mRNA (1071 bp) is submitted to ORF Finder. The return shows frame bars (from Frame +1 to Frame -3) with highlighted relative length of ORF and the list of ORF arranged according to their lengths.

Figure 10.4. Sequences of ORF nucleotide and protein translate. The sequences for nucleotides and translated amino acids from Frame +3 ORF of proopiomelanocortin DNA (Figure 10.3) are displayed by clicking SixFrame button and then activating the desired frame bar. The initiation codon (sky) and stop codon (pink) suggests potential start and end positions of CDS/translate(s) for the Frame.

Figure 10.9. Output of GeneView tool of WebGene. The DNA encoding proopiomelanocortin mRNA (1071 bp) is submitted to gene prediction by GeneView at WebGene. The output adapts GenBank format.

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