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  - Zemkova, Hana
AU  - Kucka, Marek
AU  - Bjelobaba, Ivana
AU  - Tomić, Melanija
AU  - Stojilković, Stanko S
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1065
AB  - Acetylcholine (ACh) has been established as a paracrine factor in the anterior pituitary gland, but the receptors mediating ACh action and the cell types bearing these receptors have not been identified. Our results showed that the expression of the nicotinic subunits mRNAs followed the order beta 2 > beta 1 = alpha 9 > alpha 4 in cultured rat pituitary cells. The expression of the subunits in immortalized L beta T2 mouse gonadotrophs followed the order beta 2 > alpha 4 = alpha 1. M4 > M3 muscarinic receptor mRNA were also identified in pituitary and L beta T2 cells. The treatment of cultured pituitary cells with GnRH down-regulated the expression of alpha 9 and alpha 4 mRNAs, without affecting the expression of M3 and M4 receptor mRNAs, and ACh did not alter the expression of GnRH receptor mRNA. We also performed double immunostaining to show the expression of beta 2-subunit and M4 receptor proteins in gonadotrophs. Functional nicotinic channels capable of generating an inward current, facilitation of electrical activity, and Ca2+ influx were identified in single gonadotrophs and L beta T2 cells. In both cell types, the M3 receptor-mediated, phospholipase C-dependent Ca2+ mobilization activated an outward apamin-sensitive K+ current and caused hyperpolarization. The activation of M4 receptors by ACh inhibited cAMP production and GnRH-induced LH release in a pertussis toxin-sensitive manner. We concluded that multiple cholinergic receptors are expressed in gonadotrophs and that the main secretory action of ACh is inhibitory through M4 receptor-mediated down-regulation of cAMP production. The expression of nicotinic receptors in vitro compensates for the lack of regular GnRH stimulation of gonadotrophs. (Endocrinology 154: 421-433, 2013)
T2  - Endocrinology
T1  - Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs
IS  - 1
VL  - 154
SP  - 133
EP  - 433
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1065
ER  - 

@article{
author = "Zemkova, Hana and Kucka, Marek and Bjelobaba, Ivana and Tomić, Melanija and Stojilković, Stanko S",
year = "2013",
abstract = "Acetylcholine (ACh) has been established as a paracrine factor in the anterior pituitary gland, but the receptors mediating ACh action and the cell types bearing these receptors have not been identified. Our results showed that the expression of the nicotinic subunits mRNAs followed the order beta 2 > beta 1 = alpha 9 > alpha 4 in cultured rat pituitary cells. The expression of the subunits in immortalized L beta T2 mouse gonadotrophs followed the order beta 2 > alpha 4 = alpha 1. M4 > M3 muscarinic receptor mRNA were also identified in pituitary and L beta T2 cells. The treatment of cultured pituitary cells with GnRH down-regulated the expression of alpha 9 and alpha 4 mRNAs, without affecting the expression of M3 and M4 receptor mRNAs, and ACh did not alter the expression of GnRH receptor mRNA. We also performed double immunostaining to show the expression of beta 2-subunit and M4 receptor proteins in gonadotrophs. Functional nicotinic channels capable of generating an inward current, facilitation of electrical activity, and Ca2+ influx were identified in single gonadotrophs and L beta T2 cells. In both cell types, the M3 receptor-mediated, phospholipase C-dependent Ca2+ mobilization activated an outward apamin-sensitive K+ current and caused hyperpolarization. The activation of M4 receptors by ACh inhibited cAMP production and GnRH-induced LH release in a pertussis toxin-sensitive manner. We concluded that multiple cholinergic receptors are expressed in gonadotrophs and that the main secretory action of ACh is inhibitory through M4 receptor-mediated down-regulation of cAMP production. The expression of nicotinic receptors in vitro compensates for the lack of regular GnRH stimulation of gonadotrophs. (Endocrinology 154: 421-433, 2013)",
journal = "Endocrinology",
title = "Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs",
number = "1",
volume = "154",
pages = "133-433",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1065"
}

Zemkova, H., Kucka, M., Bjelobaba, I., Tomić, M.,& Stojilković, S. S.. (2013). Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs. in Endocrinology, 154(1), 133-433.
https://hdl.handle.net/21.15107/rcub_ibiss_1065

Zemkova H, Kucka M, Bjelobaba I, Tomić M, Stojilković SS. Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs. in Endocrinology. 2013;154(1):133-433.
https://hdl.handle.net/21.15107/rcub_ibiss_1065 .

Zemkova, Hana, Kucka, Marek, Bjelobaba, Ivana, Tomić, Melanija, Stojilković, Stanko S, "Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs" in Endocrinology, 154, no. 1 (2013):133-433,
https://hdl.handle.net/21.15107/rcub_ibiss_1065 .

TY  - JOUR
AU  - Li, Shuo
AU  - Bjelobaba, Ivana
AU  - Yan, Zonghe
AU  - Kucka, Marek
AU  - Tomić, Melanija
AU  - Stojilković, Stanko S
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1120
AB  - Pannexins are a newly discovered three-member family of proteins expressed in the brain and peripheral tissues that belong to the superfamily of gap junction proteins. However, in mammals pannexins do not form gap junctions, and their expression and function in the pituitary gland have not been studied. Here we show that the rat pituitary gland expresses mRNA and protein transcripts of pannexins 1 and 2 but not pannexin 3. Pannexin 1 was more abundantly expressed in the anterior lobe, whereas pannexin 2 was more abundantly expressed in the intermediate and posterior pituitary. Pannexin 1 was identified in corticotrophs and a fraction of somatotrophs, the S100-positive pituicytes of the posterior pituitary and AtT-20 (mouse pituitary adrenocorticotropin-secreting cells) and rat immortalized pituitary cells secreting prolactin, whereas pannexin 2 was detected in the S100-positive folliculostellate cells of the anterior pituitary, melanotrophs of the intermediate lobe, and vasopressin-containing axons and nerve endings in the posterior lobe. Overexpression of pannexins 1 and 2 in AtT-20 pituitary cells enhanced the release of ATP in the extracellular medium, which was blocked by the gap junction inhibitor carbenoxolone. Basal ATP release in At-T20 cells was also suppressed by down-regulating the expression of endogenous pannexin 1 but not pannexin 2 with their short interfering RNAs. These results indicate that pannexins may provide a pathway for delivery of ATP, which is a native agonist for numerous P2X cationic channels and G protein-coupled P2Y receptors endogenously expressed in the pituitary gland. (Endocrinology 152: 2342-2352, 2011)
T2  - Endocrinology
T1  - Expression and Roles of Pannexins in ATP Release in the Pituitary Gland
IS  - 6
VL  - 152
SP  - 83
EP  - 2352
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1120
ER  - 

@article{
author = "Li, Shuo and Bjelobaba, Ivana and Yan, Zonghe and Kucka, Marek and Tomić, Melanija and Stojilković, Stanko S",
year = "2011",
abstract = "Pannexins are a newly discovered three-member family of proteins expressed in the brain and peripheral tissues that belong to the superfamily of gap junction proteins. However, in mammals pannexins do not form gap junctions, and their expression and function in the pituitary gland have not been studied. Here we show that the rat pituitary gland expresses mRNA and protein transcripts of pannexins 1 and 2 but not pannexin 3. Pannexin 1 was more abundantly expressed in the anterior lobe, whereas pannexin 2 was more abundantly expressed in the intermediate and posterior pituitary. Pannexin 1 was identified in corticotrophs and a fraction of somatotrophs, the S100-positive pituicytes of the posterior pituitary and AtT-20 (mouse pituitary adrenocorticotropin-secreting cells) and rat immortalized pituitary cells secreting prolactin, whereas pannexin 2 was detected in the S100-positive folliculostellate cells of the anterior pituitary, melanotrophs of the intermediate lobe, and vasopressin-containing axons and nerve endings in the posterior lobe. Overexpression of pannexins 1 and 2 in AtT-20 pituitary cells enhanced the release of ATP in the extracellular medium, which was blocked by the gap junction inhibitor carbenoxolone. Basal ATP release in At-T20 cells was also suppressed by down-regulating the expression of endogenous pannexin 1 but not pannexin 2 with their short interfering RNAs. These results indicate that pannexins may provide a pathway for delivery of ATP, which is a native agonist for numerous P2X cationic channels and G protein-coupled P2Y receptors endogenously expressed in the pituitary gland. (Endocrinology 152: 2342-2352, 2011)",
journal = "Endocrinology",
title = "Expression and Roles of Pannexins in ATP Release in the Pituitary Gland",
number = "6",
volume = "152",
pages = "83-2352",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1120"
}

Li, S., Bjelobaba, I., Yan, Z., Kucka, M., Tomić, M.,& Stojilković, S. S.. (2011). Expression and Roles of Pannexins in ATP Release in the Pituitary Gland. in Endocrinology, 152(6), 83-2352.
https://hdl.handle.net/21.15107/rcub_ibiss_1120

Li S, Bjelobaba I, Yan Z, Kucka M, Tomić M, Stojilković SS. Expression and Roles of Pannexins in ATP Release in the Pituitary Gland. in Endocrinology. 2011;152(6):83-2352.
https://hdl.handle.net/21.15107/rcub_ibiss_1120 .

Li, Shuo, Bjelobaba, Ivana, Yan, Zonghe, Kucka, Marek, Tomić, Melanija, Stojilković, Stanko S, "Expression and Roles of Pannexins in ATP Release in the Pituitary Gland" in Endocrinology, 152, no. 6 (2011):83-2352,
https://hdl.handle.net/21.15107/rcub_ibiss_1120 .