TY  - JOUR
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Stojilkovic, Stanko S.
AU  - Bjelobaba, Ivana
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32592862
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6149
AB  - Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
PB  - Elsevier BV
PB  - Elsevier
T2  - Brain, Behavior, and Immunity
T1  - The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
VL  - 89
DO  - 10.1016/j.bbi.2020.06.025
SP  - 233
EP  - 244
ER  - 

@article{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Božić, Iva and Milošević, Katarina and Jakovljević, Marija and Peković, Sanja and Stojilkovic, Stanko S. and Bjelobaba, Ivana",
year = "2020",
abstract = "Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.",
publisher = "Elsevier BV, Elsevier",
journal = "Brain, Behavior, and Immunity",
title = "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.",
volume = "89",
doi = "10.1016/j.bbi.2020.06.025",
pages = "233-244"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Božić, I., Milošević, K., Jakovljević, M., Peković, S., Stojilkovic, S. S.,& Bjelobaba, I.. (2020). The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity
Elsevier BV., 89, 233-244.
https://doi.org/10.1016/j.bbi.2020.06.025

Milošević A, Janjić M, Lavrnja I, Savić D, Božić I, Milošević K, Jakovljević M, Peković S, Stojilkovic SS, Bjelobaba I. The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity. 2020;89:233-244.
doi:10.1016/j.bbi.2020.06.025 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Božić, Iva, Milošević, Katarina, Jakovljević, Marija, Peković, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana, "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis." in Brain, Behavior, and Immunity, 89 (2020):233-244,
https://doi.org/10.1016/j.bbi.2020.06.025 . .

TY  - JOUR
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Stojilkovic, Stanko S.
AU  - Bjelobaba, Ivana
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32592862
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3762
AB  - Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
PB  - Elsevier BV
T2  - Brain, Behavior, and Immunity
T1  - The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
VL  - 89
DO  - 10.1016/j.bbi.2020.06.025
SP  - DOI:10.1016/j.bbi.2020.06.025
EP  - 244
ER  - 

@article{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Božić, Iva and Milošević, Katarina and Jakovljević, Marija and Peković, Sanja and Stojilkovic, Stanko S. and Bjelobaba, Ivana",
year = "2020",
abstract = "Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.",
publisher = "Elsevier BV",
journal = "Brain, Behavior, and Immunity",
title = "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.",
volume = "89",
doi = "10.1016/j.bbi.2020.06.025",
pages = "DOI:10.1016/j.bbi.2020.06.025-244"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Božić, I., Milošević, K., Jakovljević, M., Peković, S., Stojilkovic, S. S.,& Bjelobaba, I.. (2020). The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity
Elsevier BV., 89, DOI:10.1016/j.bbi.2020.06.025-244.
https://doi.org/10.1016/j.bbi.2020.06.025

Milošević A, Janjić M, Lavrnja I, Savić D, Božić I, Milošević K, Jakovljević M, Peković S, Stojilkovic SS, Bjelobaba I. The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity. 2020;89:DOI:10.1016/j.bbi.2020.06.025-244.
doi:10.1016/j.bbi.2020.06.025 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Božić, Iva, Milošević, Katarina, Jakovljević, Marija, Peković, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana, "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis." in Brain, Behavior, and Immunity, 89 (2020):DOI:10.1016/j.bbi.2020.06.025-244,
https://doi.org/10.1016/j.bbi.2020.06.025 . .

TY  - CONF
AU  - Janjić, Marija
AU  - Previde, Rafael Maso
AU  - Smiljanić, Kosara
AU  - Fletcher, Patrick A.
AU  - Sherman, Arthur
AU  - Bjelobaba, Ivana
AU  - Stojilkovic, Stanko S.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5981
AB  - Aim: To investigate mechanisms of inhibition of reproductive functions by continuous GnRH application, with focus on gonadotropin gene expression and secretion. Methods: Experiments were performed in vivo and in vitro using female and male rats and cultured pituitary cells. Gene expression was characterized by qRT-PCR analysis. For this purpose, we searched for an appropriate reference gene. Protein expression was characterized by immunocytochemistry, and ELISA and Western blot analyses were used for LH measurements. Results: Continuous exposure of pituitary cells in static cultures to Gnrh agonists induced a prolonged blockade of Fshb expression after a brief stimulation. However, only a minor and transient inhibitory effect on Lhb expression was detected. Such Lhb profile probably reflects the expression status of three genes controlling Lhb transcription during the treatment: stimulation of Egr1, inhibition of Nr5a1, and no effect on Pitx1 expression. In contrast, continuous Gnrh treatment stimulated Lh secretion in static cultures, leading to depletion of the secretory pool. In vivo administration of a Gnrh agonist was also accompanied with a rapid increase in serum Lh levels and a progressive depletion of the intrapituitary Lh levels without major effects on Lhb expression. Conclusion: Blockade of Fshb expression and depletion of the Lh secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous Gnrh treatment.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs
SP  - 367
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5981
ER  - 

@conference{
author = "Janjić, Marija and Previde, Rafael Maso and Smiljanić, Kosara and Fletcher, Patrick A. and Sherman, Arthur and Bjelobaba, Ivana and Stojilkovic, Stanko S.",
year = "2019",
abstract = "Aim: To investigate mechanisms of inhibition of reproductive functions by continuous GnRH application, with focus on gonadotropin gene expression and secretion. Methods: Experiments were performed in vivo and in vitro using female and male rats and cultured pituitary cells. Gene expression was characterized by qRT-PCR analysis. For this purpose, we searched for an appropriate reference gene. Protein expression was characterized by immunocytochemistry, and ELISA and Western blot analyses were used for LH measurements. Results: Continuous exposure of pituitary cells in static cultures to Gnrh agonists induced a prolonged blockade of Fshb expression after a brief stimulation. However, only a minor and transient inhibitory effect on Lhb expression was detected. Such Lhb profile probably reflects the expression status of three genes controlling Lhb transcription during the treatment: stimulation of Egr1, inhibition of Nr5a1, and no effect on Pitx1 expression. In contrast, continuous Gnrh treatment stimulated Lh secretion in static cultures, leading to depletion of the secretory pool. In vivo administration of a Gnrh agonist was also accompanied with a rapid increase in serum Lh levels and a progressive depletion of the intrapituitary Lh levels without major effects on Lhb expression. Conclusion: Blockade of Fshb expression and depletion of the Lh secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous Gnrh treatment.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs",
pages = "367",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5981"
}

Janjić, M., Previde, R. M., Smiljanić, K., Fletcher, P. A., Sherman, A., Bjelobaba, I.,& Stojilkovic, S. S.. (2019). Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 367.
https://hdl.handle.net/21.15107/rcub_ibiss_5981

Janjić M, Previde RM, Smiljanić K, Fletcher PA, Sherman A, Bjelobaba I, Stojilkovic SS. Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:367.
https://hdl.handle.net/21.15107/rcub_ibiss_5981 .

Janjić, Marija, Previde, Rafael Maso, Smiljanić, Kosara, Fletcher, Patrick A., Sherman, Arthur, Bjelobaba, Ivana, Stojilkovic, Stanko S., "Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):367,
https://hdl.handle.net/21.15107/rcub_ibiss_5981 .

TY  - JOUR
AU  - Bjelobaba, Ivana
AU  - Janjić, Marija
AU  - Tavcar, Jovana S.
AU  - Kucka, Marek
AU  - Tomić, Melanija
AU  - Stojilkovic, Stanko S.
PY  - 2016
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0303720716303471
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2523
AB  - Hypothalamic GnRH together with gonadal steroids and activins/inhibin regulate its receptor gene (Gnrhr) expression in vivo, which leads to crucial changes in GnRHR numbers on the plasma membrane. This is accompanied by alterations in the gonadotroph sensitivity and responsiveness during physiologically relevant situations. Here we investigated basal and GnRH-regulated Gnrhr expression in rodent pituitary gonadotrophs in vitro. In pituitary cells from adult animals cultured in the absence of GnRH and steroid hormones, the Gnrhr expression was progressively reduced but not completely abolished. The basal Gnrhr expression was also operative in LβT2 immortalized gonadotrophs never exposed to GnRH. In both cell types, basal transcription was sufficient for the expression of functional GnRHRs. Continuous application of GnRH transiently elevated the Gnrhr expression in cultured pituitary cells followed by a sustained fall without affecting basal transcription. Both basal and regulated Gnrhr transcriptions were dependent on the protein kinase C signaling pathway. The GnRH-regulated Gnrhr expression was not operative in embryonal pituitary and LβT2 cells and was established neonatally, the sex-specific response patterns were formed at the juvenile-peripubertal stage and there was a strong correlation between basal and regulated gene expression during development. Thus, the age-dependent basal and regulated Gnrhr transcription could account for the initial blockade and subsequent activation of the reproductive system during development.
PB  - Elsevier Ireland Ltd
T2  - Molecular and Cellular Endocrinology
T1  - The relationship between basal and regulated Gnrhr expression in rodent pituitary gonadotrophs
VL  - 437
DO  - 10.1016/j.mce.2016.08.040
SP  - 302
EP  - 311
ER  - 

@article{
author = "Bjelobaba, Ivana and Janjić, Marija and Tavcar, Jovana S. and Kucka, Marek and Tomić, Melanija and Stojilkovic, Stanko S.",
year = "2016",
abstract = "Hypothalamic GnRH together with gonadal steroids and activins/inhibin regulate its receptor gene (Gnrhr) expression in vivo, which leads to crucial changes in GnRHR numbers on the plasma membrane. This is accompanied by alterations in the gonadotroph sensitivity and responsiveness during physiologically relevant situations. Here we investigated basal and GnRH-regulated Gnrhr expression in rodent pituitary gonadotrophs in vitro. In pituitary cells from adult animals cultured in the absence of GnRH and steroid hormones, the Gnrhr expression was progressively reduced but not completely abolished. The basal Gnrhr expression was also operative in LβT2 immortalized gonadotrophs never exposed to GnRH. In both cell types, basal transcription was sufficient for the expression of functional GnRHRs. Continuous application of GnRH transiently elevated the Gnrhr expression in cultured pituitary cells followed by a sustained fall without affecting basal transcription. Both basal and regulated Gnrhr transcriptions were dependent on the protein kinase C signaling pathway. The GnRH-regulated Gnrhr expression was not operative in embryonal pituitary and LβT2 cells and was established neonatally, the sex-specific response patterns were formed at the juvenile-peripubertal stage and there was a strong correlation between basal and regulated gene expression during development. Thus, the age-dependent basal and regulated Gnrhr transcription could account for the initial blockade and subsequent activation of the reproductive system during development.",
publisher = "Elsevier Ireland Ltd",
journal = "Molecular and Cellular Endocrinology",
title = "The relationship between basal and regulated Gnrhr expression in rodent pituitary gonadotrophs",
volume = "437",
doi = "10.1016/j.mce.2016.08.040",
pages = "302-311"
}

Bjelobaba, I., Janjić, M., Tavcar, J. S., Kucka, M., Tomić, M.,& Stojilkovic, S. S.. (2016). The relationship between basal and regulated Gnrhr expression in rodent pituitary gonadotrophs. in Molecular and Cellular Endocrinology
Elsevier Ireland Ltd., 437, 302-311.
https://doi.org/10.1016/j.mce.2016.08.040

Bjelobaba I, Janjić M, Tavcar JS, Kucka M, Tomić M, Stojilkovic SS. The relationship between basal and regulated Gnrhr expression in rodent pituitary gonadotrophs. in Molecular and Cellular Endocrinology. 2016;437:302-311.
doi:10.1016/j.mce.2016.08.040 .

Bjelobaba, Ivana, Janjić, Marija, Tavcar, Jovana S., Kucka, Marek, Tomić, Melanija, Stojilkovic, Stanko S., "The relationship between basal and regulated Gnrhr expression in rodent pituitary gonadotrophs" in Molecular and Cellular Endocrinology, 437 (2016):302-311,
https://doi.org/10.1016/j.mce.2016.08.040 . .