Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells

Xu, Peng; Bao, Riqiang; Zhang, Yaqiong; Lu, Enhang; Feng, Fen; Zhang, Luyin; Zhang, Yingbo; Wang, Jing; Tan, Ximin; Tang, Min; Hu, Chuan; Li, Gang; Zhang, Chunping

doi:10.1002/mrd.23149

Cited by 10 publications

(17 citation statements)

References 43 publications

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“…One of these is the control of the hormonal homeostasis in regulating TRH, GnRH, and progesterone concentrations. Of note, data by Xu et al [ 73 ] demonstrating that PREP increased the expression of the steroidogenic enzymes, StAR, and 3β-HSD via the ERK signaling pathway in murine luteal cells well support our results since we also observed the increase of StAR protein level induced by MLT treatment. Thus, we may hypothesize that MLT regulates testosterone synthesis just acting on PREP expression; however, further studies are still required to confirm this point.…”

Section: Discussionsupporting

confidence: 91%

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Venditti

Rhouma

Romano

et al. 2021

Genes

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Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues, including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells and provoked testicular injury, as documented by biomolecular and histological alterations, i.e., CAT and SOD activity, the protein level of steroidogenic enzymes (StAR and 3β-HSD), and morphometric parameters. Additionally, it further documents the melatonin (MLT) coadministration produces affects in mitigating Cd-induced toxicity on adult rat testis, as demonstrated by the reduction of oxidative stress and apoptosis, with reversal of the observed histological changes; moreover, a role of MLT in partially restoring steroidogenic enzymes expression was evidenced. Importantly, the cytoarchitecture of testicular cells was perturbed by Cd exposure, as highlighted by impairment of the expression and localization of two cytoskeleton-associated proteins DAAM1 and PREP, which are involved in the germ cells’ differentiation into spermatozoa, altering the normal spermatogenesis. Here, for the first time, we found that the co-treatment with MLT attenuated the Cd-induced toxicity on the testicular DAAM1 and PREP expression. The combined findings provide additional clues about a protective effect of MLT against Cd-induced testicular toxicity by acting on DAAM1 and PREP expression, encouraging further studies to prove its effectiveness in human health.

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Section: Discussionsupporting

confidence: 91%

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Venditti

Rhouma

Romano

et al. 2021

Genes

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“…In addition to the aforementioned role exerted by PREP, the peptidase is essential for ERK and Akt pathway activations (Duan et al 2014, Xu et al 2019. Interestingly, herein, we also demonstrated that the chronic D-Asp treatment induced the phosphorylation of ERK1/2 and Akt proteins in the rat testis.…”

Section: Discussionsupporting

confidence: 73%

D-Asp upregulates PREP and GluA2/3 expressions and induces p-ERK1/2 and p-Akt in rat testis

et al. 2019

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D-Aspartate (D-Asp) is an endogenous amino acid that plays a central role in the development of the central nervous system (CNS) and functioning of the neuroendocrine system. In line with its functions, it is abundantly present in the CNS and reproductive systems of vertebrates and invertebrates. It has been implicated in the biosynthesis and/or secretion of hormones and factors that are involved in various reproductive functions, such as GnRH from the hypothalamus and testosterone from the testis. We conducted an in vivo study consisting of acute (i.p. injection of 2 µmol/g body weight) and chronic (15 days drinking solution) administration of D-Asp to adult rats to understand the signaling pathways elicited by D-Asp in the rat testis. We found that D-Asp upregulated the expression of prolyl endopeptidase (PREP), a serine protease having a pivotal role in the regulation of mammalian spermatogenesis and spermiogenesis. Immunofluorescence analysis revealed its overexpression in Leydig cells, Sertoli cells and spermatogonia. Moreover, PREP was found to co-localize with GluA2/3, an AMPA receptor subunit, whose protein expression also increased after D-Asp treatments. Finally, we found a significant increase in ERK and Akt activities in the testis of rats treated with D-Asp. Since PREP is known to be involved in regulating GnRH levels and in germ cell differentiation, we hypothesize D-Asp to play a pivotal role in regulating hormone homeostasis and spermatogenesis through activation of PREP, AMPAR, ERK and Akt.

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“…The second reason is the destruction of ovarian cells, 21,33 because estrogen is secreted by granulosa cells and respectively progesterone secreted via luteal cells. 34 On the other hand, sure decreases estrogen level and subsequently leads to abnormality in follicle growth. 24 Moreover, BaP with the downregulation of steroidogenic enzymes and the reduction in the activity of 17-β hydroxysteroid dehydrogenase (17β-HSD) decreases testosterone, estrogen, and progesterone.…”

Section: Discussionmentioning

confidence: 99%

Effect of prenatal exposure to Benzo[a]pyrene on ovarian toxicity and reproductive dysfunction: Protective effect of atorvastatin in the embryonic period

Rahmani

Malekshah

Zargari

et al. 2021

Environmental Toxicology

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As an environmental contaminant, Benzo[a]pyrene (B[a]P; BaP) disrupts the antioxidant signaling and thus leads to the induction of oxidative stress and the damage of DNA in the ovary. low-dose atorvastatin (ATV) has antioxidant and anti-apoptotic properties. The present study aimed to survey the effects of prenatal exposure to BaP on ovarian toxicity and also to investigate the protective role of ATV in reducing ovarian toxicity. In this study, rats were divided into seven groups: control, ATV (10 mg/kg), oil, BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg). BaP and ATV were administrated from gestation day 7-16 (GD7 to GD16), orally. 10 weeks after the birth, female offsprings were examined for oxidative stress markers, sex hormones, ovarian and tubular tissue structure, and the apoptosis markers. Data showed that BaP significantly reduced glutathione, increased malondialdehyde level, and disrupted the tissue structure of the ovary. Moreover, estrogen and progesterone levels significantly decreased in the offsprings rats. Also, BaP increased caspase-3 immunoreactivity. Atorvastatin treatment along with BaP in the embryonic period were able to bring the antioxidant status and sex hormones levels relatively close to normal. Besides, histological findings showed that atorvastatin was able to improve ovarian and oviduct abnormalities caused by BaP. Based on the above studies be concluded that atorvastatin in the embryonic during was able to reduce ovarian damage caused by BaP with antioxidant and anti-apoptotic properties.

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Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells

Cited by 10 publications

References 43 publications

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

D-Asp upregulates PREP and GluA2/3 expressions and induces p-ERK1/2 and p-Akt in rat testis

Effect of prenatal exposure to Benzo[a]pyrene on ovarian toxicity and reproductive dysfunction: Protective effect of atorvastatin in the embryonic period

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