Endorphins pituitary

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). 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

At the time of the discovery of Met-enkephalin, its sequence was observed to be identical to that of residues 61—65 contained in the C-fragment of the pituitary hormone p-Hpotropin [12584-99-5] (p-LPH) (see Hormones), first isolated in 1964 (11). In 1976, the isolation of a larger peptide fragment, P-endorphin [60617-12-1] that also displayed opiate-like activity was reported (12). This peptide s 31-amino-acid sequence comprised residues 61—91 of P-LPH. Subsequentiy, another potent opioid peptide, dynorphin [72957-38-17, was isolated from pituitary (13). The first five amino acids (qv) of this 17-amino-acid peptide are identical to the Leu-enkephalin sequence (see Table 1). 

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

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). 

Gianoulakis C, Beliveau D, Angelogianni P, et al Different pituitary beta-endorphin and adrenal cortisol response to ethanol in individuals with high and low risk for future development of alcoholism. Life Sci 45 1097-1109, 1989 Gianoulakis C, Krishnan B, Thavundayil J Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism. Arch Gen Psychiatry 53 250-257, 1996... 

The POMC family consists of peptides that act as hormones (ACTH, LPH, MSH) and others that may serve as neurotransmitters or neuromodulators (endorphins) (see Figure 42-15). POMC is synthesized as a precursor molecule of 285 amino acids and is processed differ-endy in various regions of the pituitary. 

The POMC gene is expressed in the anterior and intermediate lobes of the pituitary. The most conserved sequences between species are within the amino terminal fragment, the ACTH region, and the (3-endorphin region. POMC or related products are found in several other vertebrate tissues, including the brain, placenta, gastrointestinal tract, reproductive tract, lung, and lymphocytes. 

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. 

FIGURE 1 8-5 Tissue-specific processing of the pro-opiomelanocortin (POMC) precursor yields a wide array of bioactive peptide products. Processing of the POMC precursor varies in various tissues. In anterior pituitary, adrenocorticotropic hormone (ACTH (1-39)) and P-1 ipo tropin (P-LPH) are the primary products of post-translational processing. Arcuate neurons produce the potent opiate P-endorphin (P-endo (1-31)) as well as ACTIK1 -13) NIT,. Intermediate pituitary produces a-melanocyte-stimulating hormone (aMSH), acetylated P endof 1 31) and P-endo(l-27). NTS, nucleus tractus solitarius. 

There are also several reports of Li+-induced effects upon the endorphins (see ref. 162). More recently it has been shown that Li+ also enhances the activity of tyrosine aminopeptidase in rat pituitary gland [167]. This could result in changes in the levels of the enkephalins which are primarily degraded by aminopeptidases via cleavage of the tyrosine-glycine amide bond [168]. 

Hollt, V., and Bergmann, M. (1982) Effects of acute and chronic haloperidol treatment on the concentrations of immunoreactive /3-endorphin in plasma, pituitary and brain of rats. Neuropharmacology, 21 147-154. 

Hong JS, AN SF. 1982. Chlordecone (Kepone) exposure in the neonate selectively alters brain and pituitary endorphin levels in prepuberal and adult rats. Neurotoxicology 3(2) 111-117. 

Neuroendocrine In human subjects with Aizheimer s disease, intravenous infusion of arecoiine caused eievations of adrenocorticotrophic hormone, cortisoi, and j8-endorphin, indicating an activation of the hypothaiamic-pituitary-adrenai axis (Asthana etai. 1995). 

Endogenous oligopeptides that bind with parts of opioid receptors and act analogous to opioids were observed in the brain and other tissues. The first of these to be isolated and decoded were met- and leu-enkephaUn. j3-Endorphin, a peptide with quite a large molecular mass and with analogous action, was found produced in pituitary gland. 

Angiotensin II, administered into the central nervous system, increases the release of luteinizing hormone, adrenocortical hormone, thyroid-releasing hormone, (3-endorphin, vasopressin, and oxytocin from the anterior pituitary. In contrast, centrally administered angiotensin II inhibits the release of anterior pituitary growth hormone and prolactin. 

Goldstein A. Opioid peptides (endorphins) in pituitary and brain. Science 1976 193 1081-1086. 

Another example of processing of glycoproteins is found in the synthesis of pituitary hormones. ACTH, /3LPH, a-MSH, and /3-endorphin are synthesized from a common precursor in the neurointermediate lobe. Controlled, proteolytic cleavage liberates the final products, which are then secreted. Numerous other examples could be mentioned.3SS 393... 

Hollt, V., Przewlocki, R., Herz, A. fi-Endorphine-like immunoreactivity in plasma, pituitaries and hypothalamus of rats following treatment with opiates, Life Sciences 1978, 23, 1057-1066. 

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