TY  - CONF
AU  - Stojiljković, Aleksandra
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Ivanović-Šašić, Ana
AU  - Kolar-Anić, Ljiljana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6413
AB  - The previously proposed stoichiometric model of the Hypothalamic-Pituitary-Adrenal (HPA)
axis activity that took into account arginine vasopressin (AVP), has been further developed to
emulate ultradian oscillations of corticotropin-releasing hormone (CRH) and AVP. With this
aim, additional coupling of HPA consisting hormones was introduced into this model by
reaction between CRH and cortisol (CORT). How additional coupling of hormones affects HPA
axis ultradian dynamics and reflects on ultradian oscillations of AVP and CRH concentrations
was examined by using numerical simulations and bifurcation analysis. Results show that the
rate constant of newly incorporated reaction alone is sufficient to be adjusted only for CRH to
exhibit oscillations with optimally prominent amplitudes. Also, oscillation frequencies of CRH
were found to be in accordance with findings in the literature under all investigated conditions
PB  - Society of Physical Chemists of Serbia
C3  - Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia
T1  - Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol
VL  - I
SP  - 207
EP  - 210
UR  - https://hdl.handle.net/21.15107/rcub_cer_6413
ER  - 

@conference{
author = "Stojiljković, Aleksandra and Čupić, Željko and Maćešić, Stevan and Ivanović-Šašić, Ana and Kolar-Anić, Ljiljana",
year = "2022",
abstract = "The previously proposed stoichiometric model of the Hypothalamic-Pituitary-Adrenal (HPA)
axis activity that took into account arginine vasopressin (AVP), has been further developed to
emulate ultradian oscillations of corticotropin-releasing hormone (CRH) and AVP. With this
aim, additional coupling of HPA consisting hormones was introduced into this model by
reaction between CRH and cortisol (CORT). How additional coupling of hormones affects HPA
axis ultradian dynamics and reflects on ultradian oscillations of AVP and CRH concentrations
was examined by using numerical simulations and bifurcation analysis. Results show that the
rate constant of newly incorporated reaction alone is sufficient to be adjusted only for CRH to
exhibit oscillations with optimally prominent amplitudes. Also, oscillation frequencies of CRH
were found to be in accordance with findings in the literature under all investigated conditions",
publisher = "Society of Physical Chemists of Serbia",
journal = "Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia",
title = "Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol",
volume = "I",
pages = "207-210",
url = "https://hdl.handle.net/21.15107/rcub_cer_6413"
}

Stojiljković, A., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A.,& Kolar-Anić, L.. (2022). Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol. in Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 207-210.
https://hdl.handle.net/21.15107/rcub_cer_6413

Stojiljković A, Čupić Ž, Maćešić S, Ivanović-Šašić A, Kolar-Anić L. Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol. in Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia. 2022;I:207-210.
https://hdl.handle.net/21.15107/rcub_cer_6413 .

Stojiljković, Aleksandra, Čupić, Željko, Maćešić, Stevan, Ivanović-Šašić, Ana, Kolar-Anić, Ljiljana, "Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol" in Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia, I (2022):207-210,
https://hdl.handle.net/21.15107/rcub_cer_6413 .

TY  - JOUR
AU  - Stojiljković, Aleksandra S.
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Ivanović - Šašić, Ana
AU  - Kolar-Anić, Ljiljana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5390
AB  - Numerous studies on humans and animals have indicated that the corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) stimulate both individually and synergistically secretion of adrenocorticotropic hormone (ACTH) by corticotropic cells in anterior pituitary. With aim to characterize and better comprehend the mechanisms underlying the effects of AVP on Hypothalamic-Pituitary-Adrenal (HPA) axis ultradian dynamics, AVP is here incorporated into our previously proposed stoichiometric model of HPA axis in humans. This extended nonlinear network reaction model took into account AVP by: reaction steps associated with two separate inflows of AVP into pituitary portal system, that is synthesized and released from hypothalamic parvocellular and magnocellular neuronal populations, as well as summarized reaction steps related to its individual and synergistic action with CRH on corticotropic cells. To explore the properties of extended model and its capacity to emulate the effects of AVP, nonlinear dynamical systems theory and bifurcation analyses based on numerical simulations were utilized to determine the dependence of ultradian oscillations on rate constants of the inflows of CRH and AVP from parvocellular neuronal populations, the conditions under which dynamical transitions occur due to their synergistic action and, moreover, the types of these transitions. The results show that under certain conditions, HPA system could enter into oscillatory dynamic states from stable steady state and vice versa under the influence of synergy reaction rate constant. Transitions between these dynamical states were always through supercritical Andronov-Hopf bifurcation point. Also, results revealed the conditions under which amplitudes of ultradian oscillations could increase several-fold due to CRH and AVP synergistic stimulation of ACTH secretion in accordance with results reported in the literature. Moreover, results showed experimentally observed superiority of CRH as a stimulator of ACTH secretion compared to AVP in humans. The proposed model can be very useful in studies related to the role of AVP and its synergistic action with CRH in life-threatening circumstances such as acute homeostasis dynamic crisis, autoimmune inflammations or severe hypovolemia requiring instant or several-days sustained corticosteroid excess levels. Moreover, the model can be helpful for investigations of indirect AVP-induced HPA activity by exogenously administered AVP used in therapeutic treatment.
PB  - Frontiers Media S.A.
T2  - Frontiers in Endokrinology
T1  - Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis
VL  - 13
SP  - 976323
DO  - 10.3389/fendo.2022.976323
ER  - 

@article{
author = "Stojiljković, Aleksandra S. and Čupić, Željko and Maćešić, Stevan and Ivanović - Šašić, Ana and Kolar-Anić, Ljiljana",
year = "2022",
abstract = "Numerous studies on humans and animals have indicated that the corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) stimulate both individually and synergistically secretion of adrenocorticotropic hormone (ACTH) by corticotropic cells in anterior pituitary. With aim to characterize and better comprehend the mechanisms underlying the effects of AVP on Hypothalamic-Pituitary-Adrenal (HPA) axis ultradian dynamics, AVP is here incorporated into our previously proposed stoichiometric model of HPA axis in humans. This extended nonlinear network reaction model took into account AVP by: reaction steps associated with two separate inflows of AVP into pituitary portal system, that is synthesized and released from hypothalamic parvocellular and magnocellular neuronal populations, as well as summarized reaction steps related to its individual and synergistic action with CRH on corticotropic cells. To explore the properties of extended model and its capacity to emulate the effects of AVP, nonlinear dynamical systems theory and bifurcation analyses based on numerical simulations were utilized to determine the dependence of ultradian oscillations on rate constants of the inflows of CRH and AVP from parvocellular neuronal populations, the conditions under which dynamical transitions occur due to their synergistic action and, moreover, the types of these transitions. The results show that under certain conditions, HPA system could enter into oscillatory dynamic states from stable steady state and vice versa under the influence of synergy reaction rate constant. Transitions between these dynamical states were always through supercritical Andronov-Hopf bifurcation point. Also, results revealed the conditions under which amplitudes of ultradian oscillations could increase several-fold due to CRH and AVP synergistic stimulation of ACTH secretion in accordance with results reported in the literature. Moreover, results showed experimentally observed superiority of CRH as a stimulator of ACTH secretion compared to AVP in humans. The proposed model can be very useful in studies related to the role of AVP and its synergistic action with CRH in life-threatening circumstances such as acute homeostasis dynamic crisis, autoimmune inflammations or severe hypovolemia requiring instant or several-days sustained corticosteroid excess levels. Moreover, the model can be helpful for investigations of indirect AVP-induced HPA activity by exogenously administered AVP used in therapeutic treatment.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Endokrinology",
title = "Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis",
volume = "13",
pages = "976323",
doi = "10.3389/fendo.2022.976323"
}

Stojiljković, A. S., Čupić, Ž., Maćešić, S., Ivanović - Šašić, A.,& Kolar-Anić, L.. (2022). Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis. in Frontiers in Endokrinology
Frontiers Media S.A.., 13, 976323.
https://doi.org/10.3389/fendo.2022.976323

Stojiljković AS, Čupić Ž, Maćešić S, Ivanović - Šašić A, Kolar-Anić L. Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis. in Frontiers in Endokrinology. 2022;13:976323.
doi:10.3389/fendo.2022.976323 .

Stojiljković, Aleksandra S., Čupić, Željko, Maćešić, Stevan, Ivanović - Šašić, Ana, Kolar-Anić, Ljiljana, "Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis" in Frontiers in Endokrinology, 13 (2022):976323,
https://doi.org/10.3389/fendo.2022.976323 . .

TY  - CONF
AU  - Stojiljković, Aleksandra
AU  - Stanojević, Ana
AU  - Ivanović-Šašić, Ana
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6410
AB  - An upgraded model of the Hypothalamic-Pituitary-Adrenal (HPA) axis has been developed that 
advances our previously proposed low-dimensional HPA model by including the effects of arginine 
vasopressin (AVP) that is a key modulator of HPA axis function. The upgraded model allows us to 
emulate AVP effects on HPA axis dynamics individually and in synergy with the corticotropin-releasing hormone (CRH). In this work, we examine how coupling of the circadian function through 
summarised reaction steps describing CRH and AVP biosynthesis in the same neuronal cell group of the hypothalamic paraventricular nucleus (PVN) affects HPA axis dynamics. Results of numerical simulations show that coupling of the circadian function through both, CRH and AVP summarised biosynthesis reaction steps simultaneously, emulates best the HPA axis dynamics, in line with literature findings.
PB  - Society of Physical Chemists of Serbia
C3  - Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia
T1  - Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin
VL  - I
SP  - 246
EP  - 249
UR  - https://hdl.handle.net/21.15107/rcub_cer_6410
ER  - 

@conference{
author = "Stojiljković, Aleksandra and Stanojević, Ana and Ivanović-Šašić, Ana and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2021",
abstract = "An upgraded model of the Hypothalamic-Pituitary-Adrenal (HPA) axis has been developed that 
advances our previously proposed low-dimensional HPA model by including the effects of arginine 
vasopressin (AVP) that is a key modulator of HPA axis function. The upgraded model allows us to 
emulate AVP effects on HPA axis dynamics individually and in synergy with the corticotropin-releasing hormone (CRH). In this work, we examine how coupling of the circadian function through 
summarised reaction steps describing CRH and AVP biosynthesis in the same neuronal cell group of the hypothalamic paraventricular nucleus (PVN) affects HPA axis dynamics. Results of numerical simulations show that coupling of the circadian function through both, CRH and AVP summarised biosynthesis reaction steps simultaneously, emulates best the HPA axis dynamics, in line with literature findings.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia",
title = "Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin",
volume = "I",
pages = "246-249",
url = "https://hdl.handle.net/21.15107/rcub_cer_6410"
}

Stojiljković, A., Stanojević, A., Ivanović-Šašić, A., Čupić, Ž.,& Kolar-Anić, L.. (2021). Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin. in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 246-249.
https://hdl.handle.net/21.15107/rcub_cer_6410

Stojiljković A, Stanojević A, Ivanović-Šašić A, Čupić Ž, Kolar-Anić L. Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin. in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia. 2021;I:246-249.
https://hdl.handle.net/21.15107/rcub_cer_6410 .

Stojiljković, Aleksandra, Stanojević, Ana, Ivanović-Šašić, Ana, Čupić, Željko, Kolar-Anić, Ljiljana, "Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin" in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia, I (2021):246-249,
https://hdl.handle.net/21.15107/rcub_cer_6410 .