Regulation of bioactive β‐endorphin processing in rat pars intermedia

Ham, Jack; Smyth, Derek G.

doi:10.1016/0014-5793(84)80778-4

Cited by 26 publications

(9 citation statements)

References 14 publications

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“…With this procedure it became apparent that the patterns of |5-endorphin-related peptides released from rat anterior pituitary cells can vary according to whether secretion takes place under basal or stimulated conditions and whether the secretion is chronically inhib ited. As previously reported [11] acute stimulation o f ante rior pituitary cells with C R F leads to an increase in the release o f immunoreactive [i-endorphin, with a particularly marked increase in 3.5-kilodalton (f-endorphin relative to lipotropin. In the present experiments it is shown that con tinuing incubation with C R F over a period of time ( > 5 h) leads to a preferential release of lipotropin and it is accom panied by only small amounts of [f-endorphin.…”

Section: Discussionsupporting

confidence: 64%

“…In contrast, under basal condi tions it has been reported that less processed intermediates appear to predominate [2,12,15,22]. More recently it has been shown that in response to dopamine blockade rat neuro-intermediate lobe cells produce a higher proportion o f the more heavily processed forms o f (1-endorphin; in the absence of dopamine the cells generate bioactive P-endor phin as the major peptide [11]. In other studies pulse chase experiments carried out in the frog neuro-intermediate lobe have demonstrated that a -M S H (ACTH 1-13) is elaborated in the inactive des-acetyl form but on stimulation o f secre tion the acetylated peptide is released into the extracellular medium [17], These lines o f evidence indicate that during dynamic secretion the processing o f pro-opiomelanocortin (PO M C) is altered, apparently to generate higher levels of bioactive peptides.…”

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confidence: 98%

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Chronic Stimulation of Anterior Pituitary Cell Cultures with CRF Leads to the Secretion of Lipotropin

Ham¹,

Smyth²

1986

Neuroendocrinology

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Time course studies have shown that the secretion of β-endorphin-related peptides from primary cultures of rat anterior pituitary reached a plateau after 1 h of stimulation by 10^–7 Mcorticotropin-releasing factor (CRF); the major peptide released was β-endorphin 1–31. Further incubation of the cells with CRF led to a decline in the rate of secretion and to the appearance of a different pattern of peptides in which lipotropin was the principal component; analysis of the peptides remaining in the cells, however, showed that β-endorphin was still the major peptide. Chronic blockade of the anterior pituitary cells with dexamethasone (10^–6M) resulted in diminished secretion and the released peptides were found to contain a higher proportion of the intact prohormone, pro-opiomelanocortin (POMC). In all the experiments involving stimulation of the pituitary cells with CRF or blockade with corticosteroids it was observed that the pattern of secreted peptides differed from the intracellular patterns, which suggests that selective release can occur from vesicles or cells that contain different segments of POMC.

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Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 98%

Chronic Stimulation of Anterior Pituitary Cell Cultures with CRF Leads to the Secretion of Lipotropin

Ham¹,

Smyth²

1986

Neuroendocrinology

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“…The results seem to indicate that the form of processing of the TRH prohormone in the hypothalamus is different from that in the spinal cord, but it should be realised that variations in processing can occur within a single tissue. Intratissue variations have been reported for j-endorphin processing in rat pars intermedia, associated with the regulatory influence of dopamine [18], and it is possible that similar variations may occur in the processing of TRH.…”

Section: Discussionmentioning

confidence: 98%

Specific processing of the thyrotropin-releasing prohormone in rat brain and spinal cord

Cockle

Smyth

1987

Eur J Biochem

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Thyrotropin-releasing hormone (TRH) and TRH extended peptides were extracted from rat hypothalamus and spinal cord and resolved by gel exclusion chromatography under dissociating conditions. Peptides related to TRH were detected by trypsin digestion and radioimmunoassay with an antibody to TRH or an antibody raised against the pentapeptide Glp-His-Pro-Gly-Lys. In addition to the tripeptide hormone a series of C-terminally extended forms of TRH was shown to occur in both tissues; no N-terminally extended peptides were detected. The structure of the TRH-related peptides was confirmed by chromatographic identification of the N-terminal pentapeptide sequence released by trypsin.The TRH extended peptides, which accounted for 15-20% of the total TRH, were present in three groups of different molecular size corresponding to predicted fragments of the TRH prohormone. One of the peptides in the spinal cord was identified by chromatographic comparison with a synthetic 16-residue peptide representing residues 154-169 of the prohormone. In the spinal cord the TRH extended peptides differed in their relative concentrations from the corresponding peptides in the hypothalamus, possibly reflecting differences in processing. The finding of extended forms of TRH in which the extension occurs only on the C-terminal side of the hormone sequence shows that the prohormone undergoes highly specific processing.The prohormone of thyrotropin-releasing hormone (TRH) has been shown to contain multiple copies of the TRH sequence Gln-His-Pro-Gly, enclosed by pairs of consecutive basic residues and separated by intervening sequences [I, 21. By analogy with other gene-duplicated prohormones, the proteolytic processing of the TRH prohormone would be expected to take place primarily at paired basic residues sequences but the processing reactions would not be expected to go to completion. It was anticipated, therefore, that Nterminally and C-terminally extended forms of TRH would occur naturally. In previous studies we have described the preparation of an antibody to a synthetic pentapeptide which could be used to identify extended forms of TRH [3] and we were able to demonstrate their existence in Xenopus skin and bovine hypothalamus [4]. In this communication we present the results of an investigation of TRH-related peptides in the rat which reveal a striking specificity in the TRH processing in the hypothalamus and spinal cord. EXPERIMENTAL PROCEDURE tional fluorenylmethoxycarbonyl methodology [5].The imidazole group of histidine was protected by the butyloxycarbonyl substituent, the gudnidino group of arginine by the methoxytrimethylbenzene-sulphonyl substituent, the hydroxyl group of threonine and serine and the 8-and y-carboxyl groups of aspartic and glutamic acids by the t-butyl substituent. Coupling in the presence of 1-hydroxybenztriazole was effected by reaction of the pentafluorophenyl ester of the fluorenylmethoxycarbonyl-amino acids, with the exception of threonine and serine, which were used as the oxobenztriazine esters, and argini...

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“…It is thus possible that an explanation for the redundancy of the innervation may yet be found at the postsynaptic level in some differential effects of the transmitters on other functional parameters in the melano trophs, for example, gene expression, or synthesis or posttranslational processing of the secretory products. GABA, for in stance, has been observed to inhibit expression of the proopio melanocortin gene [37], And dopamine has been seen to inhibit the synthesis of proopiomelanocortin [38], and also the acetyla tion of both [Vendorphin [39,40] and «-melanocyte stimulating hormone [41,42]. But conjectures on possible differential ef fects at the postsynaptic level must confront the indications that the intracellular signals set in motion by the three transmitters in the melanotrophs appear, from current evidence, from me lanotrophs and other cells, to be similar, each involving re ductions in cyclic AMP and cytosolic Ca2+; and furthermore, that these same intracellular signals have been implicated in the regulation of gene expression and posttranslationai processing [43,44].…”

Section: Discussionmentioning

confidence: 99%

Why Are Several Inhibitory Transmitters Present in the Innervation of Pituitary Melanotrophs?

Kongsamut

Shibuya²,

Douglas³

1991

Neuroendocrinology

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The aim of the present experiments was to determine whether some rationale for the presence of the several inhibitory neurotransmitters in the innervation to the toad melanotroph might be found in differences in their individual effects or in possible cooperative interactions affecting secretion. Measurements of peptide release from isolated, perifused neurointemediate lobes of the toad Xenopus laevis showed that each of the three identified inhibitory transmitters, dopamine, GABA and NPY, was able to inhibit secretion profoundly and no less effectively than omission of Ca. Moreover, the inhibitory effects were rather similar in onset, duration and recovery. Furthermore, there was no evidence of any cooperative interactions when the transmitters were given in various combinations. And finally, the inhibitory response to each of the transmitters was abolished by pretreatment with pertussis toxin. While not excluding differential postsynaptic effects on other parameters of melanotroph function, the similarities observed have encouraged alternative speculations on the significance of the apparent redundancy of inhibitory transmitters.

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Regulation of bioactive β‐endorphin processing in rat pars intermedia

Cited by 26 publications

References 14 publications

Chronic Stimulation of Anterior Pituitary Cell Cultures with CRF Leads to the Secretion of Lipotropin

Chronic Stimulation of Anterior Pituitary Cell Cultures with CRF Leads to the Secretion of Lipotropin

Specific processing of the thyrotropin-releasing prohormone in rat brain and spinal cord

Why Are Several Inhibitory Transmitters Present in the Innervation of Pituitary Melanotrophs?

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