TY  - CONF
AU  - Sokanović, Srđan
AU  - Constantin, Stephanie
AU  - Lamarca Dams, Aloa
AU  - Mochimaru, Yuta
AU  - Smiljanić, Kosara
AU  - Bjelobaba, Ivana
AU  - Prévide, Rafael
AU  - Stojilković, Stanko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5854
AB  - Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which 
encode the protein tyrosine phosphatase receptors N and N2, respectively, causes 
infertility of female mice while males are fertile. To clarify the mechanism of sex specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects of 
their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO 
females, a delay in puberty and lack of ovulation were observed, supplemented by 
changes in ovarian gene expression and steroidogenesis. In DKO males, the testicular 
gene expression, steroidogenesis, and development of reproductive organs were not 
affected. However, in both sexes, pituitary luteinizing hormone (LH) beta gene
expression and LH levels were reduced, while the calcium-mobilizing and LH 
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were 
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also reduced 
in DKO females and males. The density of immunoreactive GnRH fibers was 
decreased in the median eminence in DKO females and males. The density of 
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular 
region of the third ventricle of females and in the arcuate nucleus of females and 
males. Therefore, infertility in DKO females cannot be explained only by sex-specific 
gonadotroph impairment. Instead, changes in hypothalamic gene expression, 
specifically Kiss1 in the rostral periventricular region of the third ventricle, might 
provide an alternative hypothesis due to its sexual dimorphism and involvement in 
puberty onset and ovulation.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function
SP  - 107
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5854
ER  - 

@conference{
author = "Sokanović, Srđan and Constantin, Stephanie and Lamarca Dams, Aloa and Mochimaru, Yuta and Smiljanić, Kosara and Bjelobaba, Ivana and Prévide, Rafael and Stojilković, Stanko",
year = "2023",
abstract = "Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which 
encode the protein tyrosine phosphatase receptors N and N2, respectively, causes 
infertility of female mice while males are fertile. To clarify the mechanism of sex specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects of 
their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO 
females, a delay in puberty and lack of ovulation were observed, supplemented by 
changes in ovarian gene expression and steroidogenesis. In DKO males, the testicular 
gene expression, steroidogenesis, and development of reproductive organs were not 
affected. However, in both sexes, pituitary luteinizing hormone (LH) beta gene
expression and LH levels were reduced, while the calcium-mobilizing and LH 
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were 
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also reduced 
in DKO females and males. The density of immunoreactive GnRH fibers was 
decreased in the median eminence in DKO females and males. The density of 
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular 
region of the third ventricle of females and in the arcuate nucleus of females and 
males. Therefore, infertility in DKO females cannot be explained only by sex-specific 
gonadotroph impairment. Instead, changes in hypothalamic gene expression, 
specifically Kiss1 in the rostral periventricular region of the third ventricle, might 
provide an alternative hypothesis due to its sexual dimorphism and involvement in 
puberty onset and ovulation.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function",
pages = "107",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5854"
}

Sokanović, S., Constantin, S., Lamarca Dams, A., Mochimaru, Y., Smiljanić, K., Bjelobaba, I., Prévide, R.,& Stojilković, S.. (2023). Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 107.
https://hdl.handle.net/21.15107/rcub_ibiss_5854

Sokanović S, Constantin S, Lamarca Dams A, Mochimaru Y, Smiljanić K, Bjelobaba I, Prévide R, Stojilković S. Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:107.
https://hdl.handle.net/21.15107/rcub_ibiss_5854 .

Sokanović, Srđan, Constantin, Stephanie, Lamarca Dams, Aloa, Mochimaru, Yuta, Smiljanić, Kosara, Bjelobaba, Ivana, Prévide, Rafael, Stojilković, Stanko, "Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):107,
https://hdl.handle.net/21.15107/rcub_ibiss_5854 .

TY  - JOUR
AU  - Sokanović, Srđan
AU  - Constantin, Stephanie
AU  - Dams, Aloa Lamarca
AU  - Mochimaru, Yuta
AU  - Smiljanić, Kosara
AU  - Bjelobaba, Ivana
AU  - Prévide, Rafael
AU  - Stojilković, Stanko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5382
AB  - Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions.
PB  - Springer Nature
T2  - Scientific Reports
T1  - Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction
VL  - 13
DO  - 10.1038/s41598-023-27497-4
SP  - 1
SP  - 355
ER  - 

@article{
author = "Sokanović, Srđan and Constantin, Stephanie and Dams, Aloa Lamarca and Mochimaru, Yuta and Smiljanić, Kosara and Bjelobaba, Ivana and Prévide, Rafael and Stojilković, Stanko",
year = "2023",
abstract = "Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions.",
publisher = "Springer Nature",
journal = "Scientific Reports",
title = "Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction",
volume = "13",
doi = "10.1038/s41598-023-27497-4",
pages = "1-355"
}

Sokanović, S., Constantin, S., Dams, A. L., Mochimaru, Y., Smiljanić, K., Bjelobaba, I., Prévide, R.,& Stojilković, S.. (2023). Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction. in Scientific Reports
Springer Nature., 13, 1.
https://doi.org/10.1038/s41598-023-27497-4

Sokanović S, Constantin S, Dams AL, Mochimaru Y, Smiljanić K, Bjelobaba I, Prévide R, Stojilković S. Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction. in Scientific Reports. 2023;13:1.
doi:10.1038/s41598-023-27497-4 .

Sokanović, Srđan, Constantin, Stephanie, Dams, Aloa Lamarca, Mochimaru, Yuta, Smiljanić, Kosara, Bjelobaba, Ivana, Prévide, Rafael, Stojilković, Stanko, "Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction" in Scientific Reports, 13 (2023):1,
https://doi.org/10.1038/s41598-023-27497-4 . .

TY  - JOUR
AU  - Janjić, Marija
AU  - Prévide, Rafael M.
AU  - Fletcher, Patrick A.
AU  - Sherman, Arthur
AU  - Smiljanić, Kosara
AU  - Abebe, Daniel
AU  - Bjelobaba, Ivana
AU  - Stojilković, Stanko S.
PY  - 2019
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6934515
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3595
AB  - Continuous, as opposed to pulsatile, delivery of hypothalamic gonadotropin-releasing hormone (GnRH) leads to a marked decrease in secretion of pituitary gonadotropins LH and FSH and impairment of reproductive function. Here we studied the expression profile of gonadotropin subunit and GnRH receptor genes in rat pituitary in vitro and in vivo to clarify their expression profiles in the absence and continuous presence of GnRH. Culturing of pituitary cells in GnRH-free conditions downregulated Fshb, Cga, and Gnrhr expression, whereas continuous treatment with GnRH agonists upregulated Cga expression progressively and Gnrhr and Fshb expression transiently, accompanied by a prolonged blockade of Fshb but not Gnrhr expression. In contrast, Lhb expression was relatively insensitive to loss of endogenous GnRH and continuous treatment with GnRH, probably reflecting the status of Egr1 and Nr5a1 expression. Similar patterns of responses were observed in vivo after administration of a GnRH agonist. However, continuous treatment with GnRH stimulated LH secretion in vitro and in vivo, leading to decrease in LH cell content despite high basal Lhb expression. These data suggest that 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.
T2  - Scientific Reports
T1  - Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.
IS  - 1
VL  - 9
DO  - 10.1038/s41598-019-56480-1
SP  - 20098
ER  - 

@article{
author = "Janjić, Marija and Prévide, Rafael M. and Fletcher, Patrick A. and Sherman, Arthur and Smiljanić, Kosara and Abebe, Daniel and Bjelobaba, Ivana and Stojilković, Stanko S.",
year = "2019",
abstract = "Continuous, as opposed to pulsatile, delivery of hypothalamic gonadotropin-releasing hormone (GnRH) leads to a marked decrease in secretion of pituitary gonadotropins LH and FSH and impairment of reproductive function. Here we studied the expression profile of gonadotropin subunit and GnRH receptor genes in rat pituitary in vitro and in vivo to clarify their expression profiles in the absence and continuous presence of GnRH. Culturing of pituitary cells in GnRH-free conditions downregulated Fshb, Cga, and Gnrhr expression, whereas continuous treatment with GnRH agonists upregulated Cga expression progressively and Gnrhr and Fshb expression transiently, accompanied by a prolonged blockade of Fshb but not Gnrhr expression. In contrast, Lhb expression was relatively insensitive to loss of endogenous GnRH and continuous treatment with GnRH, probably reflecting the status of Egr1 and Nr5a1 expression. Similar patterns of responses were observed in vivo after administration of a GnRH agonist. However, continuous treatment with GnRH stimulated LH secretion in vitro and in vivo, leading to decrease in LH cell content despite high basal Lhb expression. These data suggest that 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.",
journal = "Scientific Reports",
title = "Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.",
number = "1",
volume = "9",
doi = "10.1038/s41598-019-56480-1",
pages = "20098"
}

Janjić, M., Prévide, R. M., Fletcher, P. A., Sherman, A., Smiljanić, K., Abebe, D., Bjelobaba, I.,& Stojilković, S. S.. (2019). Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.. in Scientific Reports, 9(1), 20098.
https://doi.org/10.1038/s41598-019-56480-1

Janjić M, Prévide RM, Fletcher PA, Sherman A, Smiljanić K, Abebe D, Bjelobaba I, Stojilković SS. Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.. in Scientific Reports. 2019;9(1):20098.
doi:10.1038/s41598-019-56480-1 .

Janjić, Marija, Prévide, Rafael M., Fletcher, Patrick A., Sherman, Arthur, Smiljanić, Kosara, Abebe, Daniel, Bjelobaba, Ivana, Stojilković, Stanko S., "Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo." in Scientific Reports, 9, no. 1 (2019):20098,
https://doi.org/10.1038/s41598-019-56480-1 . .