Comparative Aspects of Intracellular Proteolytic Processing of Peptide Hormone Precursors: Studies of Proopiomelanocortin Processing

Tanaka, Shigeyasu

doi:10.2108/zsj.20.1183

Cited by 63 publications

(37 citation statements)

References 102 publications

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“…The different profiles of ACTH and α-MSH observed after PE remain to be evaluated. One hypothesis could be that E 2 may have different mechanisms of action according to the cell type (melanotrope or corticotrope cell) (Tanaka 2003;Olah et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

Gallelli¹,

Monachesi²,

Miceli³

et al. 2015

Vet. Med. - Czech

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ABSTRACT:The hypothalamic-pituitary-adrenal axis (HPA) is a complex system regulated by multiple factors. Sexual dimorphism of this axis has been described in different species under physiological conditions and it has been proposed that sexual hormones could have an effect on it. There are only a few reports about sex-linked variations in HPA axis hormones in the dog. Thus, studying the impact of sexual hormones on the HPA axis would broaden the knowledge about its function in this species. Therefore, the objective of this study was to determine whether there are variations in HPA plasma hormones (ACTH, alfa-melanocyte-stimulating hormone [α-MSH] and cortisol) according to the sex and photoperiod (positive or negative photoperiod were considered when the duration of the light hours of the day was more than 12 or less than 12, respectively) under basal conditions (like anoestrus) and throughout the oestrous cycle in the female dog. The population under study consisted of 11 intact female and 14 intact male dogs. Under basal conditions neither ACTH nor α-MSH concentrations showed differences between sexes and different photoperiods. Cortisol showed greater values in the negative photoperiod than in the positive, both in females and males (P = 0.03 and P = 0.015, respectively). Throughout the oestrous cycle, all the studied hormones showed variations (P < 0.0001). The greatest concentrations of ACTH were observed at proestrus, while α-MSH and cortisol showed their greatest concentrations at oestrus. The three hormones decreased in diestrus. ACTH and cortisol concentrations were higher in the negative photoperiod (P = 0.04 and P < 0.0001, respectively), while α-MSH concentrations were higher in the positive photoperiod (P = 0.012). In the group of females oestradiol and progesterone correlated with ACTH (r = 0.75, P < 0.0001; r = 0.34, P < 0.01, respectively), α-MSH (r = 0.49, P < 0.0001; r = 0.52, P < 0.0001, respectively) and cortisol (r = 0.33, P < 0.01; r = 0.5, P < 0.0001, respectively). These results show that in females, HPA axis hormones vary during the oestrous cycle in relation to oestradiol and progesterone fluctuations. The ACTH, α-MSH and cortisol concentrations also showed differences between photoperiods in females, but only cortisol did so in males. These findings suggest that sexual hormones could have an effect on the HPA axis. Further research needs to be done to fully understand this interaction and the mechanisms involved.

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Section: Discussionmentioning

confidence: 99%

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

Gallelli¹,

Monachesi²,

Miceli³

et al. 2015

Vet. Med. - Czech

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“…Tanaka S et al [12] reported that proPC2 with 638 amino acid residues (74 kDa) is activated into mature PC2 with 529 amino acid residues (64 kDa) in adequate conditions, such as pH 5.0, other PCs and higher Ca 2+ . The soluble CPE (sCPE) is an exopeptidase that cleaves neuro-endocrinopeptides with C-terminal basic amino acids and produces active forms of peptide hormones and neuropeptides [13,14] .…”

Section: Introductionmentioning

confidence: 99%

视网膜神经节细胞-5应激损伤后原蛋白转化酶-2和羧基肽酶-E介导的神经肽加工

Tang

Zhang²,

Liu³

et al. 2009

Neurosci. Bull.

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Objective To observe the change of the neuropeptide pro-protein processing system in the ischemic retina ganglion cell-5 (RGC-5) cells, pro-protein convertase-2 (PC2), carboxypeptidase-E (CPE) and preproneuropeptide Y (preproNPY) protein levels in the ischemic RGC-5 cells and conditioned medium were analyzed. Methods The RGC-5 cell was differentiated in 0.1 μmol/L staurosporine for 24 h and then stressed by different doses of oxygen and glucose deprivation (OGD). The acute or chronic OGD-induced cell death rates were obtained by using PI or TUNEL staining. The protein expression levels were determined by using the Western blot method and PC2 activity analysis. Results The ischemia caused substantial cell death in an OGD dose-dependent manner. In the cells, proPC2 and preproNPY protein levels gradually increased whereas proCPE gradually decreased. After OGD, PC2 activity was decreased. In the conditioned medium, proPC2 and PC2 proteins gradually decreased whereas proCPE, CPE, and preproNPY proteins gradually increased. Conclusion These results demonstrated that OGD inhibited the neuropeptide pro-protein processing system by reducing PC2 activity and the maturation of proPC2. The aggregation of the pro-proteins and the increase of the active CPE excision adversely exacerbated the cell injury. The pro-protein processing system might play a critical role in the ischemic stress of RGC-5 cells.

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“…Clinical signs, plasma ACTH and α-MSH, the cortisol/creatinine (RC/C) urine ratio and pituitary MRI were assessed and compared at different time points [58]. In dogs, two convertase enzymes are involved in processing the POMC gene products, one active in anterior pituitary cells secreting ACTH, whereas the other is located in the intermediate-lobe cells secreting α-MSH [59]. Therefore not only ACTH but also α-MSH was assessed.…”

Section: In Vivo Data: Experimental Cushing's Disease In Nude Micementioning

confidence: 99%

Potential of retinoic acid derivatives for the treatment of corticotroph pituitary adenomas

Labeur

Paez-Pereda²,

Arzt

et al. 2008

Rev Endocr Metab Disord

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Cushing's disease is a severe clinical condition caused by hypersecretion of corticosteroids due to excessive ACTH secretion from a pituitary adenoma. This complex endocrine disorder still represents a major challenge for the physician in terms of efficient treatment. In the last years there was only little progress in elucidating the molecular mechanisms responsible for the constitutive and autonomous ACTH secretion of pituitary corticotrophinomas. As a consequence, no effective drug therapy is currently available, particularly if surgical excision is not successful. In the present article we examine recent studies that have investigated the therapeutic potential of retinoic acid receptors as nuclear receptor targets for the treatment of Cushing's disease. Retinoic acid is an efficient drug used for the treatment of different types of cancers and it proved to act in animal models of Cushing's disease. The efficiency of this treatment in patients with this disorder still needs to be tested in clinical trials.

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Comparative Aspects of Intracellular Proteolytic Processing of Peptide Hormone Precursors: Studies of Proopiomelanocortin Processing

Cited by 63 publications

References 102 publications

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

视网膜神经节细胞-5应激损伤后原蛋白转化酶-2和羧基肽酶-E介导的神经肽加工

Potential of retinoic acid derivatives for the treatment of corticotroph pituitary adenomas

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