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

Ham, Jack; Smyth, Derek G.

doi:10.1159/000124683

Cited by 17 publications

(14 citation statements)

References 22 publications

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“…This is not surprising in light of the fact that the intracellular peptide content represents total peptide levels comprised of peptides con tained within heterogeneous secretory granules. It is pos sible that in some secretory granules, POMC undergoes only limited proteolysis, such that these granules contain PLPH as the primary end product [22], In other granules, POMC may be more extensively processed, such that PE is the primary end product [22], In addition, one type of granule may be more 'releasable' (that is, available for release) than the other, perhaps by virtue of its proximity to the plasma membrane. The mechanism(s) underlying the modulation by ILip and CRH of the secreted and/or intracellular proportions of pE relative to PLPH are not known.…”

Section: Discussionmentioning

confidence: 99%

“…However, the mature end product is not necessarily that which is preferentially secreted upon corticotroph activation. Indeed, the type and duration of corticotroph stimulation have been demonstrated to alter dramatically the relative amounts of secreted pE and PLPH [22][23][24], Therefore, the generation, within a single cell, of several peptides possessing such a diverse array of biological activities necessitates the existence of an exqui sitely fine-tuned regulation of POMC gene expression and of POMC peptide processing, secretion and content. This suggests that the biochemical dynamics of the POMC molecule may be influenced by regulatory factors at sever al levels (transcriptional, translational and post-translational) and that different regulatory factors may be char acterized by distinct POMC modulatory profiles.…”

Section: Introductionmentioning

confidence: 99%

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Differential Cellular Regulation of Pro-Opiomelanocortin by Interleukin-1-Beta and Corticotropin-Releasing Hormone

Ruzicka

Akil

1995

Neuroendocrinology

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Considerable evidence supports the existence of a bidirectional communication between the immune system and the hypothalamo-pituitary-adrenal (HPA) axis. In the present study, we examined the interleukin-1β (IL1β)-mediated regulation of pro-opiomelanocortin (POMC) at a cellular level, from secretion to gene expression, using murine anterior pituitary corticotroph tumor (AtT20) cells as a model system. The regulatory effects of IL1 β were compared to those of the classical POMC regulator, corticotropin-releasing hormone (CRH). IL1β was found to evoke an early, preferential release of β-lipotropin (βLPH) which was accompanied by elevations in POMC heteronuclear (hn)RNA and c-fos and c-jun mRNAs. IL1β also elicited a late, preferential release of βLPH which was associated with only an enhanced expression of POMC hnRNA. Additionally, IL1β stimulated an intermediate, preferential release of β-endorphin (βE) which was not accompanied by any changes in gene expression. In marked contrast to IL1β, CRH evoked an early, preferential βE secretory response which was associated with elevations in POMC hnRNA and c-fos mRNA. CRH also elicited a late, preferential βE release which was associated with only an enhanced POMC hnRNA expression. These findings show that although both IL1 β and CRH activate the corticotrophs, they elicit dramatically different patterns in the regulation of the biochemical dynamics of POMC. Such distinct patterns of corticotroph activation in response to IL1β or CRH exposure in vivo would allow the pituitary not only to indicate that it has been activated, but also how it has been activated. This characteristic may be critically important in the function of the HPA axis and in the interaction of the HPA axis with the immune system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Cellular Regulation of Pro-Opiomelanocortin by Interleukin-1-Beta and Corticotropin-Releasing Hormone

Ruzicka

Akil

1995

Neuroendocrinology

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“…Since the proteolytic cleav age of POMC follows an ordered sequence which occurs in a time-ordered manner [12], the increase in the time available for processing may allow the MSH-producing enzyme to split more MSH. A second explanation stems from our observation that CRF administration eliminated the presence of MSH in grafts, an effect which was not elicited by the intact pituitary since it was also observed in hypophysectomized rats.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of the Pituitary Pars distalis Induces the Corticotrophs to Store Melanocyte-Stimulating Hormone, an Effect Reversed by the Administration of Corticotropin-Releasing Factor

Iturriza

Ferese-Spinelli

1991

Neuroendocrinology

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Corticotrophs of the pituitary pars distalis do not contain immunohistochemically detectable α-melanocyte-stimulating hormone (MSH). After grafting the glands beneath the renal capsule for 25 days, this hormone could be demonstrated in corticotrophs, coexisting with corticotropin. The administration of corticotropin-releasing factor deprived these cells of the content of MSH but did not apparently affect the presence of adrenocorticotropin (ACTH). It is suggested that the histological appearance of MSH in the corticotrophs may be due to a diminished rate of corticotropin release, which may provide time for splitting the former hormone in amounts larger than the negligible ones normally present in the pars distalis, or to the hypothetical fact that some hypothalamic factor may inhibit the cleavage of ACTH into MSH.

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“…It has, however, been shown that relatively minor changes in biochemical structure such as C-terminal trimming (12), a-amidation and a-Nacetylation (1 3) have profound effects on biological activity. There is now increasing evidence to suggest that, in addition to regulating POMC biosynthesis and release of POMC products, physiological regulators such as CRF and glucocorticoids may play a role in regulating the complex pattern of POMC processing (9,14,15).…”

Section: Discussionmentioning

confidence: 99%

“…This enzyme, plus increased carboxypeptidase activity (or a specific glucocorticoid-sensitive enzyme), may thus be crucial in the generation of NacaEP, the principal acetylated species produced in the abattoir/glucocorticoid-treated anterior pituitaries. Another possibility is the differential accumulation of the various POMC products in subpopulations of POMC-producing cells (19,20), which may be sensitive to different regulatory mechanisms (2 I), perhaps reflecting a heterogeneous distribution of releasable pools, as suggested by Ham and Smyth (9,14). The possibility also remains that these processing effects simply represent a change in intracellular steady state.…”

Section: Discussionmentioning

confidence: 99%

Stress‐Related Changes in β‐Endorphin Processing: The Limitations of Slaughterhouse Material

Smith

Wallace

Clarke

et al. 1989

J Neuroendocrinology

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In the sheep, unlike many other species, a significant proportion ( > 25%) of immunoreactive P-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, a-N-acetylated forms. In a study to determine the precise molecular nature of a-Nacetylated P-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex-and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated P-endorphin processing were reproduced in farm animals by chronic ( 5 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated 8-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather t h a n a direct effect on t h e pituitary, and (3) t h e relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions.The stress-induced release of adrenocorticotropin (ACTH), Pendorphin (PEP), P-lipotropin (PLPH) and other proopiomelanocortin (P0MC)-derived peptides from the anterior pituitary (AP) I \ mediated by hypothalamic-releasing factors secreted into the hypophyseal portal blood system. Synthesis of POMC, and release of processed POMC-derived peptides, are stimulated by both corticotropin-releasing factor (CRF) and arginine vasopresb i n , with other hypothalamic agents possibly involved (1). The AP corticotrope is also subject to inhibitory control by direct glucocorticoid feedback from the adrenal gland (2-4). Glucocorticoids not only inhibit ACTH/BEP release, but also negatively regulate I'OMC gene expression in the AP (5-7). In addition, the synthetic glucocorticoid dexamethasone administered in vivo causes a rapid decrease in C R F content of rat median eminence (8), evidence that glucocorticoids regulate release of POMC products from the AP b y central as well as direct effects. Finally, in addition to regulating biosynthesis of POMC and secretion of its products, glucocorticoids and CRF in vitro (9) have been shown to modulate the pattern of POMC processing in cultured rat AP cells.In the AP of the sheep, in contrast to the rat, a significant proportion ( > 25%) of PEP is a-N-acetylated; that this does not represent intermediate lobe contamination has been shown by \\edge dissection of the neurointermediate lobe, and confirmed by immunocytochemistry (10). The present study was initially undertaken to characterize the precise molecular species of immunoreactive a-N-acetylated endorphin (NacEP) in sheep AP extracts.The immunoreactive profiles, determined by reversed-phase (RP) HPLC and RIA specific for the a-N-acetylated NH, terminus of PEP, differed quite markedly in farm sheep from those observed in age-, sex-and strain-matched slaughterhouse anim...

show abstract

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

Cited by 17 publications

References 22 publications

Differential Cellular Regulation of Pro-Opiomelanocortin by Interleukin-1-Beta and Corticotropin-Releasing Hormone

Differential Cellular Regulation of Pro-Opiomelanocortin by Interleukin-1-Beta and Corticotropin-Releasing Hormone

Transplantation of the Pituitary Pars distalis Induces the Corticotrophs to Store Melanocyte-Stimulating Hormone, an Effect Reversed by the Administration of Corticotropin-Releasing Factor

Stress‐Related Changes in β‐Endorphin Processing: The Limitations of Slaughterhouse Material

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