Examination of PACAP-Like Immunoreactivity in Urogenital Tumor Samples

Tamás, Andrea; Javorhazy, Andras; Reglődi, Dóra; Sarlós, Donát Péter; Banyai, Daniel; Semjén, Dávid; Németh, József; Lelesz, Beáta; Fulop, Daniel Balazs; Szántó, Zalán

doi:10.1007/s12031-015-0652-0

Cited by 19 publications

(19 citation statements)

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“…Interestingly, unlike in other tissues, PACAP38 and 27 were found to have the same levels in human testis as shown by radioimmunoassay (Tamas et al 2016). No differences were found in the level of PACAP peptides between normal tissues and seminomas (Tamas et al 2016), but a different distribution pattern was observed in different tumor biopsies by Nakamura et al (2014). In addition to the local production of PACAP, circulating PACAP can additionally contribute to testicular functions of the peptide, as it has been shown that PACAP can cross the blood-testis barrier (Banks et al 1993, Mizushima et al 2001.…”

Section: Discussionmentioning

confidence: 53%

“…A testis-specific splice variant of the PAC1 receptor has also been reported (Daniel et al 2001). Interestingly, unlike in other tissues, PACAP38 and 27 were found to have the same levels in human testis as shown by radioimmunoassay (Tamas et al 2016). No differences were found in the level of PACAP peptides between normal tissues and seminomas (Tamas et al 2016), but a different distribution pattern was observed in different tumor biopsies by Nakamura et al (2014).…”

Section: Discussionmentioning

confidence: 61%

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Disturbed spermatogenic signaling in pituitary adenylate cyclase activating polypeptide-deficient mice

et al. 2018

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PACAP is a neuropeptide with diverse functions in various organs, including reproductive system. It is present in the testis in high concentrations, and in addition to the stage-specific expression within the seminiferous tubules, PACAP affects spermatogenesis and the functions of Leydig and Sertoli cells. Mice lacking endogenous PACAP show reduced fertility, but the possibility of abnormalities in spermatogenic signaling has not yet been investigated. Therefore, we performed a detailed morphological analysis of spermatozoa, sperm motility and investigated signaling pathways that play a role during spermatogenesis in knockout mice. No significant alterations were found in testicular morphology or motility of sperm in homozygous and heterozygous PACAP-deficient mice in spite of the moderately increased number of severely damaged sperms. However, we found robust changes in mRNA and/or protein expression of several factors that play an important role in spermatogenesis. Protein kinase A expression was markedly reduced, while downstream phospho-ERK and p38 were elevated in knockout animals. Expression of major transcription factors, such as Sox9 and phospho-Sox9, was decreased, while that of Sox10, as a redundant factor, was increased in PACAP-deficient mice. The reduced phospho-Sox9 expression was partly due to increased expression and activity of phosphatase PP2A in knockout mice. Targets of Sox transcription factors, such as collagen type IV, were reduced in knockout mice. In summary, our results show that lack of PACAP leads to disturbed signaling in spermatogenesis, which could be a factor responsible for reduced fertility in PACAP knockout mice, and further support the role of PACAP in reproduction.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 61%

Disturbed spermatogenic signaling in pituitary adenylate cyclase activating polypeptide-deficient mice

et al. 2018

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“…In another recent study, no alterations in PACAP-LI between healthy and tumoral samples from the urinary bladder and testis were detected, but lower PACAP38-LI was found in kidney tumors compared with healthy tissue samples, and higher PACAP27-LI in prostatic cancer compared to samples from benign prostatic hyperplasia [ 46 ]. These data indicate that PACAP levels of different tissue samples are altered under pathological conditions suggesting a potential role of PACAP on tumor growth [ 46 ]. Reduction of PACAPcontaining nerve fi bers was described in a few conditions, such as in women with polycystic ovaries [ 47 ].…”

Section: Concluding Remarks: Future Perspectives and Limitationsmentioning

confidence: 84%

“…Signifi cantly higher tissue levels were also shown in cardiac tissue obtained from patients with ischemic heart disease [ 45 ], while lower levels/downregulation were found in other diseases: in lung and colon cancer samples [ 45 ]. In another recent study, no alterations in PACAP-LI between healthy and tumoral samples from the urinary bladder and testis were detected, but lower PACAP38-LI was found in kidney tumors compared with healthy tissue samples, and higher PACAP27-LI in prostatic cancer compared to samples from benign prostatic hyperplasia [ 46 ]. These data indicate that PACAP levels of different tissue samples are altered under pathological conditions suggesting a potential role of PACAP on tumor growth [ 46 ].…”

Section: Concluding Remarks: Future Perspectives and Limitationsmentioning

confidence: 94%

PACAP as a Potential Biomarker: Alterations of PACAP Levels in Human Physiological and Pathological Conditions

Reglődi

Helyes

Németh

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with wide distribution and diverse effects. Its presence has not only been revealed in the nervous system and peripheral organs, but also in the blood and other biological fl uids. Although PACAP is rapidly cleaved in the blood by peptidases, increasing number of evidence has been published in the last 10 years that show alterations of PACAP levels in different pathological conditions. The present review summarizes results obtained in the human blood and other fl uids under normal, physiological and pathological conditions with clinical relevance, such as pregnancy and delivery, as well as in several diseases. Most clinical data have been obtained so far in neurological diseases, such as Alzheimer's disease, migraine, traumatic brain injury, multiple sclerosis, and cerebral hemorrhage, but some other diseases have also been shown to be accompanied by alterations of PACAP levels. These results indicate that the altered levels may have diagnostic and/or prognostic values in several diseases.

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“…PACAP alterations have been observed in several diseases in both tissue samples and body fluids including plasma, cerebrospinal fluid and follicular fluid [16,49]. Recent studies have shown that PACAP levels were lower in lung cancer, colon and kidney tumor samples compared to healthy tissue, while higher in prostate cancer samples compared with samples from benign prostatic hyperplasia [50,51]. As PACAP is indicated as a potential biomarker for various conditions by several studies, it would be important to conduct a clinical study including enough pathological placenta samples to draw final conclusions (clinical review: see Reglodi et al in this book, chapter 2.…”

Section: Expression Of Pacap In Pathological Pregnanciesmentioning

confidence: 99%

Occurrence and Functions of PACAP in the Placenta

Horváth

Németh

Brubel

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide with a widespread distribution both in the nervous system and peripheral organs. The peptide is also present in the female gonadal system, indicating its role in reproductive functions. While a lot of data are known on PACAP-induced effects in oogenesis and in the regulation of gonadotropin secretion at pituitary level, its placental effects are somewhat neglected in spite of the documented implantation deficit in mice lacking endogenous PACAP. The aim of the present review is to give a brief summary on the occurrence and actions of PACAP and its receptors in the placenta. Radioimmunoassay (RIA) measurements revealed increased serum PACAP levels during the third trimester and several changes in placental PACAP content in obstetrical pathological conditions, further supporting the function of PACAP during pregnancy. Both the peptide and its receptors have been shown in different parts of the placenta and the umbilical cord. PACAP influences blood vessel and smooth muscle contractility of the uteroplacental unit and is involved in regulation of local hormone secretion. The effects of PACAP on trophoblast cells have been mainly studied in vitro. Effects of PACAP on cell survival, angiogenesis and invasion/proliferation have been described in different trophoblast cell lines. PACAP increases proliferation and decreases invasion in proliferative extravillous trophoblast cells, but not in primary trophoblast cells, where PACAP decreased the secretion of various angiogenic markers. PACAP pretreatment enhances survival of non-tumorous primary trophoblast cells exposed to oxidative stress, but it does not influence the cell death-inducing effects of methotrexate in proliferative extravillous cytotrophoblast cells. Interestingly, PACAP has pro-apoptotic effect in choriocarcinoma cells suggesting that the effect of PACAP depends on the type of trophoblast cells. These data strongly support that PACAP plays a role in normal and pathological pregnancies and our review provides an overview of currently available experimental data worth to be further investigated to elucidate the exact role of this peptide in the placenta. Abstract Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide with a widespread distribution both in the nervous system and peripheral organs. The peptide is also present in the female gonadal system, indicating its role in reproductive functions. While a lot of data are known on PACAP-induced effects in oogenesis and in the regulation of gonadotropin secretion at pituitary level, its placental effects are somewhat neglected in spite of the documented implantation deficit in mice lacking endogenous PACAP. The aim of the present review is to give a brief summary on the occurrence and actions of PACAP and its receptors in the placenta. Radioimmunoassay (RIA) measurements revealed increased serum PACAP levels during the third trimester and several changes in placental PACAP conten...

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Examination of PACAP-Like Immunoreactivity in Urogenital Tumor Samples

Cited by 19 publications

References 70 publications

Disturbed spermatogenic signaling in pituitary adenylate cyclase activating polypeptide-deficient mice

Disturbed spermatogenic signaling in pituitary adenylate cyclase activating polypeptide-deficient mice

PACAP as a Potential Biomarker: Alterations of PACAP Levels in Human Physiological and Pathological Conditions

Occurrence and Functions of PACAP in the Placenta

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