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Huda Akil - One of the best experts on this subject based on the ideXlab platform.

  • altered ratios of beta endorphin beta Lipotropin released from anterior lobe corticotropes with increased secretory drive i effects of diminished glucocorticoid secretion
    Journal of Neuroendocrinology, 1993
    Co-Authors: Elizabeth A Young, Stanley J. Watson, Ryszard Przewlocki, Paresh D Patel, Huda Akil
    Abstract:

    Previous studies have demonstrated that acute stress or ovine corticotropin-releasing hormone (oCRH) in vivo, or oCRH in vitro, stimulates release of 8-endorphin over 8-Lipotropin from anterior pituitary corticotropes. This occurs despite the predominance of j-Iipotropin in corticotrope peptide stores. In vitro studies with primary anterior pituitary cultures suggested that chronic exposure to oCRH results in a shift towards more P-Lipotropin secretion into the media than with short-term exposure. The current studies explored whether increased secretory drive in vivo results in a similar shift towards more 8-Lipotropin. We used removal of glucocorticoids by adrenalectomy or metyrapone blockade of corticosterone synthesis, to stimulate endogenous secretion of CRH and vasopressin. Both treatments resulted in shifts of the ratio of 8-endorphin : P-Lipotropin in plasma of experimental animals in comparison to the sham-treated control rats. In vitro testing with oCRH of anterior lobe cultures from adrenalectomized or metyrapone-treated rats demonstrated similar effects of these treatments on the ratio of P-endorphin : 8-Lipotropin. These changes occurred despite similar ratios of 8-endorphin : 8-Lipotropin in anterior pituitary peptide stores. Adrenocorticotropin (ACTH) and P-endorphin are synthesized as part of a larger precursor molecule known as proopionielanocortin (POMC). The anterior pituitary corticotrope processes the C-terminal region of POMC to ACTH and either 8Lipotropin (P-LPH) or 8-endorphin, with P-LPH predominating over 8-endorphin as the end product of processing by 2- to 3-fold (I. 2). Despite the predominance of 8-LPH over 8endorphin in the total stores of anterior pituitary corticotropes, we have demonstrated that acute stress or ovine corticotropinreleasing hormone (oCRH) in vitro leads to the preferential release of 8-endorphin over P-LPH from anterior lobe corticotrope in rats (3). A similar preferential release of 8-endorphin over 1-LPH was demonstrated in man following oCRH infusion or electrically-induced seizures, suggesting that P-endorphin predominates over 8-LPH in the releasable pools of corticotropes (4, 5). However, the effects of chronic exposure to CRH on the ratio of 8-endorphin to 8-LPH in the corticotrope’s releasable pools is less clear. Chronic CRH exposure of anterior pituitary primary cell cultures has been shown to have a number of biosynthetic effects which could impact upon releasable pools in the corticotrope. For example, continuous CRH exposure in vitro leads to an increase in ACTH and P-endorphin/B-LPH released into the media over time as well as an increase in

  • altered ratios of beta endorphin beta Lipotropin released from anterior lobe corticotropes with increased secretory drive ii repeated stress
    Journal of Neuroendocrinology, 1993
    Co-Authors: Elizabeth A Young, Stanley J. Watson, R Day, Martin K H Schafer, Huda Akil
    Abstract:

    A number of stimuli including acute footshock and electrically-induced seizures lead to release of beta-endorphin immunoreactivity from the anterior pituitary corticotropes. Gel filtration of this beta-endorphin immunoreactivity indicates that approximately 3-fold more beta-endorphin than beta-Lipotropin is released into plasma following these acute stressors. A similar preponderance of beta-endorphin over beta-Lipotropin is seen in the media of short-term anterior lobe cell suspensions stimulated with ovine corticotropin-releasing hormone. Previous studies indicated that footshock stress, when administered repeatedly, can increase the biosynthesis of anterior lobe proopiomelanocortin (POMC) as indicated by increased steady state adrenocorticotropin/beta-endorphin content as well as increased POMC mRNA levels and increased POMC biosynthesis and rate of processing as measured by pulse-labeling and pulse-chase studies. The goal of the present studies was to determine whether this increased biosynthetic drive results in an alteration in the end products secreted with repeated stress. Acute footshock in a rat which has received 14 days of chronic footshock releases proportionately more beta-Lipotropin than is released in a naive rat. Chronic electrically-induced seizures, which also increase anterior lobe POMC derived peptide stores, lead to a similar shift in the ratio of beta-Lipotropin:beta-endorphin released following stress. These data suggest that chronic drive and the subsequent changes in POMC peptide stores may lead to a decrease in the proportion of beta-endorphin size immunoreactivity in the releasable pool of the anterior lobe corticotrope, thus altering the hormonal signal from the anterior lobe corticotrope.

Shosaku Numa - One of the best experts on this subject based on the ideXlab platform.

  • isolation and characterization of the bovine corticotropin β Lipotropin precursor gene
    FEBS Journal, 2005
    Co-Authors: Shigetada Nakanishi, Hisato Jingami, Masaharu Noda, Hitoshi Kakidani, Mitsue Notake, Yumiko Watanabe, Yutaka Teranishi, Shosaku Numa
    Abstract:

    The entire bovine corticotropin/β-Lipotropin precursor gene has been isolated as a set of overlapping genomic DNA fragments which extend over a length of approximately 17000 base pairs. Restriction mapping of the cloned DNA fragments and nucleotide sequence analysis of the whole mRNA-coding segments and their surrounding regions have established that the corticotropin/β-Lipotropin precursor gene is approximately 7300-basepairs long and contains two intervening sequences; one with an approximate length of 4000 base pairs is located within the segment encoding the 5′-untranslated region of the mRNA, and the other with an approximate length of 2200 base pairs interrupts the protein-coding sequence near the signal peptide region. Sequence analysis of more than 200 base pairs preceding the proximal end of the corticotropin/(f-Lipotropin precursor gene has revealed a ‘Hogness box’ and a variant of the model sequence as well as palindrome structures as observed in other eukarvotic genes. Furthermore, some sequence similarities in the 5′-flanking region are found between the corticotropin/β-Lipotropin precursor gene and the mouse α-globin and β-globin genes, all of which are negatively regulated by glucocorticoids. At least four homologous repetitive sequences are distributed at 3000–5000-base-pair distances in the corticotropin/β-Lipotropin precursor gene region; two such sequences are located in the 5′-flanking region, and one within each intervening sequence. Blot hybridization analysis of bovine pituitary nuclear RNA has indicated that the entire corticotropin/β-Lipotropin precursor gene 1S transcribed into a primary hnRNA product, which is then spliced to forth the mature mRNA.

Elizabeth A Young - One of the best experts on this subject based on the ideXlab platform.

  • altered ratios of beta endorphin beta Lipotropin released from anterior lobe corticotropes with increased secretory drive i effects of diminished glucocorticoid secretion
    Journal of Neuroendocrinology, 1993
    Co-Authors: Elizabeth A Young, Stanley J. Watson, Ryszard Przewlocki, Paresh D Patel, Huda Akil
    Abstract:

    Previous studies have demonstrated that acute stress or ovine corticotropin-releasing hormone (oCRH) in vivo, or oCRH in vitro, stimulates release of 8-endorphin over 8-Lipotropin from anterior pituitary corticotropes. This occurs despite the predominance of j-Iipotropin in corticotrope peptide stores. In vitro studies with primary anterior pituitary cultures suggested that chronic exposure to oCRH results in a shift towards more P-Lipotropin secretion into the media than with short-term exposure. The current studies explored whether increased secretory drive in vivo results in a similar shift towards more 8-Lipotropin. We used removal of glucocorticoids by adrenalectomy or metyrapone blockade of corticosterone synthesis, to stimulate endogenous secretion of CRH and vasopressin. Both treatments resulted in shifts of the ratio of 8-endorphin : P-Lipotropin in plasma of experimental animals in comparison to the sham-treated control rats. In vitro testing with oCRH of anterior lobe cultures from adrenalectomized or metyrapone-treated rats demonstrated similar effects of these treatments on the ratio of P-endorphin : 8-Lipotropin. These changes occurred despite similar ratios of 8-endorphin : 8-Lipotropin in anterior pituitary peptide stores. Adrenocorticotropin (ACTH) and P-endorphin are synthesized as part of a larger precursor molecule known as proopionielanocortin (POMC). The anterior pituitary corticotrope processes the C-terminal region of POMC to ACTH and either 8Lipotropin (P-LPH) or 8-endorphin, with P-LPH predominating over 8-endorphin as the end product of processing by 2- to 3-fold (I. 2). Despite the predominance of 8-LPH over 8endorphin in the total stores of anterior pituitary corticotropes, we have demonstrated that acute stress or ovine corticotropinreleasing hormone (oCRH) in vitro leads to the preferential release of 8-endorphin over P-LPH from anterior lobe corticotrope in rats (3). A similar preferential release of 8-endorphin over 1-LPH was demonstrated in man following oCRH infusion or electrically-induced seizures, suggesting that P-endorphin predominates over 8-LPH in the releasable pools of corticotropes (4, 5). However, the effects of chronic exposure to CRH on the ratio of 8-endorphin to 8-LPH in the corticotrope’s releasable pools is less clear. Chronic CRH exposure of anterior pituitary primary cell cultures has been shown to have a number of biosynthetic effects which could impact upon releasable pools in the corticotrope. For example, continuous CRH exposure in vitro leads to an increase in ACTH and P-endorphin/B-LPH released into the media over time as well as an increase in

  • altered ratios of beta endorphin beta Lipotropin released from anterior lobe corticotropes with increased secretory drive ii repeated stress
    Journal of Neuroendocrinology, 1993
    Co-Authors: Elizabeth A Young, Stanley J. Watson, R Day, Martin K H Schafer, Huda Akil
    Abstract:

    A number of stimuli including acute footshock and electrically-induced seizures lead to release of beta-endorphin immunoreactivity from the anterior pituitary corticotropes. Gel filtration of this beta-endorphin immunoreactivity indicates that approximately 3-fold more beta-endorphin than beta-Lipotropin is released into plasma following these acute stressors. A similar preponderance of beta-endorphin over beta-Lipotropin is seen in the media of short-term anterior lobe cell suspensions stimulated with ovine corticotropin-releasing hormone. Previous studies indicated that footshock stress, when administered repeatedly, can increase the biosynthesis of anterior lobe proopiomelanocortin (POMC) as indicated by increased steady state adrenocorticotropin/beta-endorphin content as well as increased POMC mRNA levels and increased POMC biosynthesis and rate of processing as measured by pulse-labeling and pulse-chase studies. The goal of the present studies was to determine whether this increased biosynthetic drive results in an alteration in the end products secreted with repeated stress. Acute footshock in a rat which has received 14 days of chronic footshock releases proportionately more beta-Lipotropin than is released in a naive rat. Chronic electrically-induced seizures, which also increase anterior lobe POMC derived peptide stores, lead to a similar shift in the ratio of beta-Lipotropin:beta-endorphin released following stress. These data suggest that chronic drive and the subsequent changes in POMC peptide stores may lead to a decrease in the proportion of beta-endorphin size immunoreactivity in the releasable pool of the anterior lobe corticotrope, thus altering the hormonal signal from the anterior lobe corticotrope.

Hansjorg Teschemacher - One of the best experts on this subject based on the ideXlab platform.

  • preoperative concentration of β Lipotropin immunoreactive material in cerebrospinal fluid a predictor of postoperative pain
    Neuropeptides, 2006
    Co-Authors: Reginald Matejec, J Muhling, Rolfhasso Bodeker, Gunter Hempelmann, Axel Schulz, Holger Uhlich, Hansjorg Teschemacher
    Abstract:

    Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid (CSF) have been reported to correlate inversely with postoperative morphine requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for sensitivity to postoperative pain, we determined authentic beta-endorphin (beta-endorphin(1-31)), beta-Lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)), immediately after termination of propofol infusion and still under spinal anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin IRM and beta-Lipotropin IRM were found to be increased after terminating the propofol infusion with spinal anesthesia still effective at t(B). Patients did not feel pain at times t(A), t(B) or t(D); however, they reported moderate to considerable pain at t(C). There were no correlations of postoperative pain severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM concentrations in CSF. In contrast, we observed significant inverse correlations (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for postoperative pain severity with beta-Lipotropin IRM concentrations in CSF at t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity appeared to be dependent on a central system controlling sensitivity to pain, linked to a POMC system releasing beta-Lipotropin IRM into CSF and already active at times t(A) and t(B). We conclude that beta-Lipotropin IRM in CSF might be considered to serve as a predictor of sensitivity to postoperative pain.

  • plasma levels of corticotroph type pro opiomelanocortin derivatives such as beta Lipotropin beta endorphin 1 31 or adrenocorticotropic hormone are correlated with severity of postoperative pain
    The Clinical Journal of Pain, 2006
    Co-Authors: Reginald Matejec, Rolfhasso Bodeker, Gunter Hempelmann, Heinzw Harbach, Hansjorg Teschemacher
    Abstract:

    Background:In the pituitary of lower species, pro-opiomelanocortin is expressed in corticotroph cells of the anterior and in melanotroph cells of the neurointermediate lobe; enzymatic processing in the corticotrophs results in the release of adrenocorticotropic hormone, β-Lipotropin, or β-endorphin.

Shigetada Nakanishi - One of the best experts on this subject based on the ideXlab platform.

  • isolation and characterization of the bovine corticotropin β Lipotropin precursor gene
    FEBS Journal, 2005
    Co-Authors: Shigetada Nakanishi, Hisato Jingami, Masaharu Noda, Hitoshi Kakidani, Mitsue Notake, Yumiko Watanabe, Yutaka Teranishi, Shosaku Numa
    Abstract:

    The entire bovine corticotropin/β-Lipotropin precursor gene has been isolated as a set of overlapping genomic DNA fragments which extend over a length of approximately 17000 base pairs. Restriction mapping of the cloned DNA fragments and nucleotide sequence analysis of the whole mRNA-coding segments and their surrounding regions have established that the corticotropin/β-Lipotropin precursor gene is approximately 7300-basepairs long and contains two intervening sequences; one with an approximate length of 4000 base pairs is located within the segment encoding the 5′-untranslated region of the mRNA, and the other with an approximate length of 2200 base pairs interrupts the protein-coding sequence near the signal peptide region. Sequence analysis of more than 200 base pairs preceding the proximal end of the corticotropin/(f-Lipotropin precursor gene has revealed a ‘Hogness box’ and a variant of the model sequence as well as palindrome structures as observed in other eukarvotic genes. Furthermore, some sequence similarities in the 5′-flanking region are found between the corticotropin/β-Lipotropin precursor gene and the mouse α-globin and β-globin genes, all of which are negatively regulated by glucocorticoids. At least four homologous repetitive sequences are distributed at 3000–5000-base-pair distances in the corticotropin/β-Lipotropin precursor gene region; two such sequences are located in the 5′-flanking region, and one within each intervening sequence. Blot hybridization analysis of bovine pituitary nuclear RNA has indicated that the entire corticotropin/β-Lipotropin precursor gene 1S transcribed into a primary hnRNA product, which is then spliced to forth the mature mRNA.