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Title:Učinki dolgotrajnega tretiranja s sildenafil citratom na produkcijo testosterona starih samcev laboratorijskih podgan
Authors:ID Šarlah, Karmen (Author)
ID Lipovšek, Saška (Mentor) More about this mentor... New window
Files:.pdf MAG_Sarlah_Karmen_2016.pdf (1,72 MB)
MD5: E7242F93FCB68B297C56EABD9EF865F8
 
Language:Slovenian
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:FNM - Faculty of Natural Sciences and Mathematics
Abstract:Namen magistrske naloge je bil raziskati učinke dolgotrajnega in vivo tretiranja starih samcev laboratorijskih podgan s sildenafil citratom (zaviralec fosfodiesteraze tipa 5, PDE5) na produkcijo testosterona. Raziskave so potekale v laboratoriju na Naravoslovni-matematični fakulteti Univerze v Novem Sadu od januarja do julija 2015. Zanimalo nas je, ali se s starostjo zmanjšuje koncentracija serumskega testosterona in kako šestmesečno tretiranje s sildenafil citratom vpliva na produkcijo androgenov, nitritov in ključnega proteina, ki sodeluje pri sintezi androgenov, tj. steroidogenega akutno regulatornega proteina (StAR), ter encima solubilna gvanilil ciklaza (sGC-ß1), ki sintetizira cGMP. Analizirali smo ultrastrukturo Leydigovih celic netretiranih in tretiranih osebkov. Po šestmesečnem tretiranju s sildenafil citratatom (1,25 mg/kg telesne mase), smo podgane žrtvovali in merili koncentracije preiskovanih spremenljivk v serumu, testikularni intersticijski tekočini (TIF) in Leydigovih celicah. S transmisijsko elektronsko mikroskopijo smo pregledali ultratanke tkivne rezine. Rezultati so bili skladni z navedbami v literaturi. Koncentracija androgenov se je s starostjo na splošno zniževala, medtem ko so se pri tretiranih osebkih te vrednosti bistveno povečale. Koncentracija nitritov se je s starostjo osebkov zviševala, po tretiranju pa zniževala. Koncentracija StAR se je po tretiranju povečala, medtem ko je koncentracija sGC-ß1 upadla. Vidne so bile tudi spremembe v ultrastrukturi Leydigovih celic; v tretiranih osebkih je s starostjo plazmalema postajala vse bolj gladka, z manj izrastki in v citoplazmi je bilo manj endoplazmatskega retikuluma kot v citoplazmi mlajših osebkov. V vseh tretiranih samcih, mlajših in starejših, smo opazili povečane mitohondrije zaradi večje steroidogene aktivnosti celic. Plazmalema Leydigovih celic mlajših tretiranih osebkov je bila mestoma diferencirana v izrastke, ki niso bili tako izraziti kot pri netretiranih osebkih iste starosti. Plazmalema celic starejših tretiranih osebkov je bila nediferencirana, tako da je bil rob celice videti gladek. V citoplazmi Leydigovih celic ostarelih tretiranih in netretiranih osebkov so bili prisotni elektronsko gosti lipidni vključki.
Keywords:Leydigove celice, sildenafil citrat, testosteron, StAR, solubilna gvanilil ciklaza, struktura celic
Place of publishing:Maribor
Publisher:[K. Šarlah]
Year of publishing:2016
PID:20.500.12556/DKUM-61467 New window
UDC:615.2:612.616.31(043.2)
COBISS.SI-ID:22714888 New window
NUK URN:URN:SI:UM:DK:YCJ2EIBX
Publication date in DKUM:25.10.2016
Views:1760
Downloads:239
Metadata:XML DC-XML DC-RDF
Categories:FNM
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Secondary language

Language:English
Title:Effects of Long-Term Treatment with Sildenafil Citrate on Production of Testosterone in Old Male Laboratory Rats
Abstract:The purpose of master's thesis was to investigate the effects of long-term treatment with sildenafil citrate (PDE5 inhibitor; 1.25 mg/kg body weight) on Leydig cell testosterone production in old male laboratory rats. The research was conducted in the laboratory at the Faculty of Sciences at University of Novi Sad, between January and July 2015. We were interested in whether the decline in testosterone production is age-related and how a 6-month treatment with sildenafil citrate influences the Leydig cell testosterone and nitrites production. Aditionally the level of steroidogenic acute regulatory protein (StAR) and enzyme soluble guanylyl cyclase (sGC-ß1), involved in cGMP production, were measured in Leydig cells. At the end of 6-months treatment, animals were quickly decapitated without anesthesia and we performed hormone assays. We also focused on the possible changes in ultrastructure of Leydig cells of untreated and treated old rats. Results showed decreased serum, intertesticular and Leydig cells testosterone in aged rats (12 −18 months) accompanied with increased nitrite levels. In Leydig cells, aging caused increased expression of StAR but decreased sGC-ß1. Sildenafil treatment partially restored testosterone and nitrites prouction as well as StAR and sGC-ß1 expression in Leydig cells. Furthermore, there were visible changes in ultrastructure of Leydig cells during aging, the edge of the cell was becoming smoother and there was less visible endoplasmic reticulum. In sildenafil-treated specimens we observed enlarged mitochondria due to increased steroidogenic activity. In cytoplasm of treated and untreated 18-months old rats were present electronically dense lipid incusions. Altogether, results indicate that age-dependent decreased testosterone production is followed by increased nitrite production, whereas long-term treatment with sildenafil citrate improves the declined function of Leydig cells.
Keywords:Leydig cell, sildenafil citrate, testosterone, StAR, soluble guanylyl cyclase, cell structure


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