TY  - CONF
AU  - Šošić-Jurjević, Branka 
AU  - Jovanović, Ljubiša
AU  - Marina, Ljiljana
AU  - Ristić, Nataša
AU  - Miler, Marko
AU  - Ajdžanović, Vladimir
AU  - Filipović, Branko
AU  - Luetjohann, Dieter
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4975
AB  - The cholesterol oxidation product 27-hydroxycholesterol (27OHC) is enzymatically
produced from cholesterol by CYP27A1 in an alternative pathway of
cholesterol degradation to bile acids. This oxysterol also acts as an endogenous
selective estrogen receptor modulator (SERM). In healthy humans its
concentration in circulation increases in hypercholesterolemia and with age,
and is associated with increased risk of atherosclerosis, cardiovascular diseases
and breast cancer. Several drugs with SERM activity used for treatments of breast
cancer or osteoporosis have been reported to have sporadic hepatotoxic effects.
Women suffer from some liver diseases more commonly (acute liver failure,
autoimmune hepatitis, benign liver lesions, or primary biliary cirrhosis). For all of
these the incidence increases with advancing age. To the best of our knowledge,
there is no information in the literature, clinical or experimental, relating changes
in hepatic 27OHC with incidence of liver disease in the context of aging and sex.
To address this problem, we examined the effect of age and sex on liver and serum
concentrations of 27OHC, as well as the immunostaining pattern of CYP27A1 in
the liver of four-month and 24-month-old Wistar rats (experiments were repeated
twice with similar results, nZ5-6 animals/group) using LC MS/MS and
immunohistochemistry, respectively. Furthermore, we examined changes in
total cholesterol and concentration in liver and serum, liver histopathology, as
well as serum concentration of hepatic enzymes, alanine (ALT) and aspartate
aminotransferase (AST). The effect of age (P!0.05) on increase of serum and
hepatic 27OHC was obtained both in males and females (P!0.05) and followed
the same pattern of age-related total cholesterol increase (P!0.05). However, the
intrahepatic increase of 27OHC was dramatically more pronounced only in oldaged
females (P!0.0001). CYP27A1 immunostaining intensity was similar in all
experimental groups, being the strongest in the cytoplasm of centrilobular
hepatocytes, but the immunopositivity was diffusely spread throughout the liver
lobule. Histopathological analysis revealed age-related hepatocellular degeneration
(swelling and hydropic degeneration, increased fraction of binuclear
hepatocytes and focal fatty changes) only in females. Moreover, age-related
elevation of alanine transaminase (ALT) was observed only in female rats (P!
0.01). In conclusion, the obtained results confirmed age-related female-specific
increase of hepatic 27OHC as well as hepatocyte degeneration obsereved only in
the liver of rat females. These age-related adaptive changes in cholesterol
metabolism may atenuate hepatoprotective estrogen-like effects in the liver.
PB  - bioscientifica
C3  - 24th European Congress of  Endocrinology 2022; 21–24 May 2022; Milan, Italy
T1  - Is age-related hepatic elevation of endogenous SERM 27-hydroxycho lesterol associated with hepatocellular degeneration female-specific? - Results from Rat study?
DO  - 10.1530/endoabs.81.P615
SP  - P615
ER  - 

@conference{
author = "Šošić-Jurjević, Branka  and Jovanović, Ljubiša and Marina, Ljiljana and Ristić, Nataša and Miler, Marko and Ajdžanović, Vladimir and Filipović, Branko and Luetjohann, Dieter",
year = "2022",
abstract = "The cholesterol oxidation product 27-hydroxycholesterol (27OHC) is enzymatically
produced from cholesterol by CYP27A1 in an alternative pathway of
cholesterol degradation to bile acids. This oxysterol also acts as an endogenous
selective estrogen receptor modulator (SERM). In healthy humans its
concentration in circulation increases in hypercholesterolemia and with age,
and is associated with increased risk of atherosclerosis, cardiovascular diseases
and breast cancer. Several drugs with SERM activity used for treatments of breast
cancer or osteoporosis have been reported to have sporadic hepatotoxic effects.
Women suffer from some liver diseases more commonly (acute liver failure,
autoimmune hepatitis, benign liver lesions, or primary biliary cirrhosis). For all of
these the incidence increases with advancing age. To the best of our knowledge,
there is no information in the literature, clinical or experimental, relating changes
in hepatic 27OHC with incidence of liver disease in the context of aging and sex.
To address this problem, we examined the effect of age and sex on liver and serum
concentrations of 27OHC, as well as the immunostaining pattern of CYP27A1 in
the liver of four-month and 24-month-old Wistar rats (experiments were repeated
twice with similar results, nZ5-6 animals/group) using LC MS/MS and
immunohistochemistry, respectively. Furthermore, we examined changes in
total cholesterol and concentration in liver and serum, liver histopathology, as
well as serum concentration of hepatic enzymes, alanine (ALT) and aspartate
aminotransferase (AST). The effect of age (P!0.05) on increase of serum and
hepatic 27OHC was obtained both in males and females (P!0.05) and followed
the same pattern of age-related total cholesterol increase (P!0.05). However, the
intrahepatic increase of 27OHC was dramatically more pronounced only in oldaged
females (P!0.0001). CYP27A1 immunostaining intensity was similar in all
experimental groups, being the strongest in the cytoplasm of centrilobular
hepatocytes, but the immunopositivity was diffusely spread throughout the liver
lobule. Histopathological analysis revealed age-related hepatocellular degeneration
(swelling and hydropic degeneration, increased fraction of binuclear
hepatocytes and focal fatty changes) only in females. Moreover, age-related
elevation of alanine transaminase (ALT) was observed only in female rats (P!
0.01). In conclusion, the obtained results confirmed age-related female-specific
increase of hepatic 27OHC as well as hepatocyte degeneration obsereved only in
the liver of rat females. These age-related adaptive changes in cholesterol
metabolism may atenuate hepatoprotective estrogen-like effects in the liver.",
publisher = "bioscientifica",
journal = "24th European Congress of  Endocrinology 2022; 21–24 May 2022; Milan, Italy",
title = "Is age-related hepatic elevation of endogenous SERM 27-hydroxycho lesterol associated with hepatocellular degeneration female-specific? - Results from Rat study?",
doi = "10.1530/endoabs.81.P615",
pages = "P615"
}

Šošić-Jurjević, B., Jovanović, L., Marina, L., Ristić, N., Miler, M., Ajdžanović, V., Filipović, B.,& Luetjohann, D.. (2022). Is age-related hepatic elevation of endogenous SERM 27-hydroxycho lesterol associated with hepatocellular degeneration female-specific? - Results from Rat study?. in 24th European Congress of  Endocrinology 2022; 21–24 May 2022; Milan, Italy
bioscientifica., P615.
https://doi.org/10.1530/endoabs.81.P615

Šošić-Jurjević B, Jovanović L, Marina L, Ristić N, Miler M, Ajdžanović V, Filipović B, Luetjohann D. Is age-related hepatic elevation of endogenous SERM 27-hydroxycho lesterol associated with hepatocellular degeneration female-specific? - Results from Rat study?. in 24th European Congress of  Endocrinology 2022; 21–24 May 2022; Milan, Italy. 2022;:P615.
doi:10.1530/endoabs.81.P615 .

Šošić-Jurjević, Branka , Jovanović, Ljubiša, Marina, Ljiljana, Ristić, Nataša, Miler, Marko, Ajdžanović, Vladimir, Filipović, Branko, Luetjohann, Dieter, "Is age-related hepatic elevation of endogenous SERM 27-hydroxycho lesterol associated with hepatocellular degeneration female-specific? - Results from Rat study?" in 24th European Congress of  Endocrinology 2022; 21–24 May 2022; Milan, Italy (2022):P615,
https://doi.org/10.1530/endoabs.81.P615 . .

TY  - JOUR
AU  - Vujović, Svetlana
AU  - Kanazir, Selma
AU  - Ivović, Miomira
AU  - Tančić-Gajić, Milina
AU  - Perović, Milka
AU  - Baltić, Svetlana
AU  - Marina, Ljiljana
AU  - Barać, Marija
AU  - Ivanišević, Maja
AU  - Micić, Jelena
AU  - Micić, Dragan
PY  - 2013
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/392
AB  - Introduction. Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis.
AB  - Uvod. Prevremena insuficijencija jajnika (PIJ) se odlikuje amenorejom, hipergonadotropizmom i hipoestrogenijom kod žena mlađih od 40 godina. Osteoporoza je kasna komplikacija ovog stanja. Cilja rada. Cilj istraživanja je bio da se uporede genski polimorfizam kolagena tip I alfa 1 (COLIA1) sa gustinom koštane mase kod žena sa PIJ. Metode rada. Određivan je COLIA1 genotip SS, Ss i ss kod 66 žena sa PIJ pomoću eseja za reakciju lančanog umnožavanja DNK (engl. polymerase chain reaction - PCR). Polimorfizam jednog nukleotida (zamena G u T) u okviru Sp1 vezujućeg mesta u prvom intronu gena COLIA1 određivan je primenom PCR, nakon čega se pristupilo analizi konformacionog polimorfizma. Gustina koštane mase je merena na nivou lumbalnog dela kičme pomoću apsorpciometrije. Hormonske analize za folikulostimulišući hormon, luteinizirajući hormon, estradiol, prolaktin, progesteron i testosteron urađene su primenom metoda RIA. Pri statističkoj obradi podataka korišćeni su: Kraskal-Volisov (Kruskal-Wallis) ANOVA test, χ2-test i Spirmanov (Spearman) test korelacije. Rezultati. Relativna distribucija alela COLIA1 genotipa bila je: SS 54,4%, Ss 41,0% i ss 4,5%. Nije utvrđena značajna razlika između grupa prema genotipu za gustinu koštane mase, starost ispitanica, period amenoreje ili indeks telesne mase žena. Značajna pozitivna korelacija je uočena za indeks telesne mase i paritet. Zaključak. COLIA1 je samo jedan od mnogih gena koji utiču na karakteristike kosti. Kod žena starije životne dobi on može biti marker kvaliteta, kvantiteta i osetljivosti kosti. Kod mladih žena sa PIJ COLIA1 ne može da ukaže na one žene kod kojih postoji veći rizik za nastanak osteoporoze.
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Genski polimorfizam kolagena tip I alfa 1 u prevremenoj insuficijenciji jajnika
T1  - Collagen type I alpha 1 gene polymorphism in premature ovarian failure
IS  - 5-6
VL  - 141
SP  - 344
EP  - 348
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_392
ER  - 

@article{
author = "Vujović, Svetlana and Kanazir, Selma and Ivović, Miomira and Tančić-Gajić, Milina and Perović, Milka and Baltić, Svetlana and Marina, Ljiljana and Barać, Marija and Ivanišević, Maja and Micić, Jelena and Micić, Dragan",
year = "2013, 2013",
abstract = "Introduction. Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis., Uvod. Prevremena insuficijencija jajnika (PIJ) se odlikuje amenorejom, hipergonadotropizmom i hipoestrogenijom kod žena mlađih od 40 godina. Osteoporoza je kasna komplikacija ovog stanja. Cilja rada. Cilj istraživanja je bio da se uporede genski polimorfizam kolagena tip I alfa 1 (COLIA1) sa gustinom koštane mase kod žena sa PIJ. Metode rada. Određivan je COLIA1 genotip SS, Ss i ss kod 66 žena sa PIJ pomoću eseja za reakciju lančanog umnožavanja DNK (engl. polymerase chain reaction - PCR). Polimorfizam jednog nukleotida (zamena G u T) u okviru Sp1 vezujućeg mesta u prvom intronu gena COLIA1 određivan je primenom PCR, nakon čega se pristupilo analizi konformacionog polimorfizma. Gustina koštane mase je merena na nivou lumbalnog dela kičme pomoću apsorpciometrije. Hormonske analize za folikulostimulišući hormon, luteinizirajući hormon, estradiol, prolaktin, progesteron i testosteron urađene su primenom metoda RIA. Pri statističkoj obradi podataka korišćeni su: Kraskal-Volisov (Kruskal-Wallis) ANOVA test, χ2-test i Spirmanov (Spearman) test korelacije. Rezultati. Relativna distribucija alela COLIA1 genotipa bila je: SS 54,4%, Ss 41,0% i ss 4,5%. Nije utvrđena značajna razlika između grupa prema genotipu za gustinu koštane mase, starost ispitanica, period amenoreje ili indeks telesne mase žena. Značajna pozitivna korelacija je uočena za indeks telesne mase i paritet. Zaključak. COLIA1 je samo jedan od mnogih gena koji utiču na karakteristike kosti. Kod žena starije životne dobi on može biti marker kvaliteta, kvantiteta i osetljivosti kosti. Kod mladih žena sa PIJ COLIA1 ne može da ukaže na one žene kod kojih postoji veći rizik za nastanak osteoporoze.",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Genski polimorfizam kolagena tip I alfa 1 u prevremenoj insuficijenciji jajnika, Collagen type I alpha 1 gene polymorphism in premature ovarian failure",
number = "5-6",
volume = "141",
pages = "344-348",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_392"
}

Vujović, S., Kanazir, S., Ivović, M., Tančić-Gajić, M., Perović, M., Baltić, S., Marina, L., Barać, M., Ivanišević, M., Micić, J.,& Micić, D.. (2013). Genski polimorfizam kolagena tip I alfa 1 u prevremenoj insuficijenciji jajnika. in Srpski arhiv za celokupno lekarstvo, 141(5-6), 344-348.
https://hdl.handle.net/21.15107/rcub_ibiss_392

Vujović S, Kanazir S, Ivović M, Tančić-Gajić M, Perović M, Baltić S, Marina L, Barać M, Ivanišević M, Micić J, Micić D. Genski polimorfizam kolagena tip I alfa 1 u prevremenoj insuficijenciji jajnika. in Srpski arhiv za celokupno lekarstvo. 2013;141(5-6):344-348.
https://hdl.handle.net/21.15107/rcub_ibiss_392 .

Vujović, Svetlana, Kanazir, Selma, Ivović, Miomira, Tančić-Gajić, Milina, Perović, Milka, Baltić, Svetlana, Marina, Ljiljana, Barać, Marija, Ivanišević, Maja, Micić, Jelena, Micić, Dragan, "Genski polimorfizam kolagena tip I alfa 1 u prevremenoj insuficijenciji jajnika" in Srpski arhiv za celokupno lekarstvo, 141, no. 5-6 (2013):344-348,
https://hdl.handle.net/21.15107/rcub_ibiss_392 .