TY  - JOUR
AU  - Milošević, Verica
AU  - Severs, Walter B
AU  - Ristić, Nataša
AU  - Manojlović-Stojanoski, Milica
AU  - Popovska-Perčinić, Florina V
AU  - Šošić-Jurjević, Branka 
AU  - Pendovski, Lazo B
AU  - Trifunović, Svetlana
AU  - Miler, Marko
AU  - Ajdžanović, Vladimir
PY  - 2018
UR  - http://www.hh.um.es/Abstracts/Vol_/_/__11984.htm
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3103
AB  - Genistein (G) and related soy phytoestrogens have been studied for potential usefulness in different chronic diseases, and may ameliorate signs of aging. They have a profound influence on the hypothalamo-pituitary-adrenal (HPA) axis. The present study utilized the rat model of mild andropause to thoroughly evaluate the effects of G and soy extract on the adrenal gland and related blood hormones. Adult male rats were orchidectomized (Orx) or sham operated (SO). Orx rats received daily subcutaneous injections for 3 weeks of solvent, or G (Orx+G, 30 mg/kg), or commercial soy extract (Orx+Soy, 30 mg/kg). Adrenal glands and blood were harvested at the end of the treatment for hormone analyses, histology and design-based stereology. Compared to SO rats Orx evoked significant (P<0.05) changes including: the replicating cell number in the 3 adrenocortical zones; vascularity and cortical volume and blood levels of adrenocorticotropic hormone (ACTH), aldosterone and dehydroepiandrosterone (DHEA). When comparing Orx vs. Orx+G groups the following significant (P<0.05) changes were observed: a further increase in number of replicating cells in zonas glomerulosa and reticularis, vasculature network presence, cortical and zona reticularis volumes, ACTH and corticosterone concentrations, and lower DHEA levels. Comparing Orx vs. Orx+Soy resulted in elevated (P<0.05) ACTH and corticosterone levels. Structural integrity of the adrenal gland was unchanged vs. SO rats. Overall, G and soy extract treatments resulted in proliferative activity and/or vasculature support in the adrenal cortex. The data and current literature support the impression of a beneficial effect of soy components on the homeostatic response to stress.
T2  - Histology and Histopathology
T1  - Soy isoflavone effects on the adrenal glands of orchidectomized adult male rats: a comprehensive histological and hormonal study.
IS  - 8
VL  - 33
DO  - 10.14670/HH-11-984
SP  - 843
EP  - 857
ER  - 

@article{
author = "Milošević, Verica and Severs, Walter B and Ristić, Nataša and Manojlović-Stojanoski, Milica and Popovska-Perčinić, Florina V and Šošić-Jurjević, Branka  and Pendovski, Lazo B and Trifunović, Svetlana and Miler, Marko and Ajdžanović, Vladimir",
year = "2018",
abstract = "Genistein (G) and related soy phytoestrogens have been studied for potential usefulness in different chronic diseases, and may ameliorate signs of aging. They have a profound influence on the hypothalamo-pituitary-adrenal (HPA) axis. The present study utilized the rat model of mild andropause to thoroughly evaluate the effects of G and soy extract on the adrenal gland and related blood hormones. Adult male rats were orchidectomized (Orx) or sham operated (SO). Orx rats received daily subcutaneous injections for 3 weeks of solvent, or G (Orx+G, 30 mg/kg), or commercial soy extract (Orx+Soy, 30 mg/kg). Adrenal glands and blood were harvested at the end of the treatment for hormone analyses, histology and design-based stereology. Compared to SO rats Orx evoked significant (P<0.05) changes including: the replicating cell number in the 3 adrenocortical zones; vascularity and cortical volume and blood levels of adrenocorticotropic hormone (ACTH), aldosterone and dehydroepiandrosterone (DHEA). When comparing Orx vs. Orx+G groups the following significant (P<0.05) changes were observed: a further increase in number of replicating cells in zonas glomerulosa and reticularis, vasculature network presence, cortical and zona reticularis volumes, ACTH and corticosterone concentrations, and lower DHEA levels. Comparing Orx vs. Orx+Soy resulted in elevated (P<0.05) ACTH and corticosterone levels. Structural integrity of the adrenal gland was unchanged vs. SO rats. Overall, G and soy extract treatments resulted in proliferative activity and/or vasculature support in the adrenal cortex. The data and current literature support the impression of a beneficial effect of soy components on the homeostatic response to stress.",
journal = "Histology and Histopathology",
title = "Soy isoflavone effects on the adrenal glands of orchidectomized adult male rats: a comprehensive histological and hormonal study.",
number = "8",
volume = "33",
doi = "10.14670/HH-11-984",
pages = "843-857"
}

Milošević, V., Severs, W. B., Ristić, N., Manojlović-Stojanoski, M., Popovska-Perčinić, F. V., Šošić-Jurjević, B., Pendovski, L. B., Trifunović, S., Miler, M.,& Ajdžanović, V.. (2018). Soy isoflavone effects on the adrenal glands of orchidectomized adult male rats: a comprehensive histological and hormonal study.. in Histology and Histopathology, 33(8), 843-857.
https://doi.org/10.14670/HH-11-984

Milošević V, Severs WB, Ristić N, Manojlović-Stojanoski M, Popovska-Perčinić FV, Šošić-Jurjević B, Pendovski LB, Trifunović S, Miler M, Ajdžanović V. Soy isoflavone effects on the adrenal glands of orchidectomized adult male rats: a comprehensive histological and hormonal study.. in Histology and Histopathology. 2018;33(8):843-857.
doi:10.14670/HH-11-984 .

Milošević, Verica, Severs, Walter B, Ristić, Nataša, Manojlović-Stojanoski, Milica, Popovska-Perčinić, Florina V, Šošić-Jurjević, Branka , Pendovski, Lazo B, Trifunović, Svetlana, Miler, Marko, Ajdžanović, Vladimir, "Soy isoflavone effects on the adrenal glands of orchidectomized adult male rats: a comprehensive histological and hormonal study." in Histology and Histopathology, 33, no. 8 (2018):843-857,
https://doi.org/10.14670/HH-11-984 . .

TY  - JOUR
AU  - Nesić, Dejan M
AU  - Stevanović, Darko M
AU  - Stanković, Sanja Đ
AU  - Milošević, Verica
AU  - Trajković, Vladimir S
AU  - Starčević, Vesna P.
AU  - Severs, Walter B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/997
AB  - Ghrelin is an endogenous peptide potentially useful in therapy of anorexia and other age-related metabolic disturbances. We evaluated the influence of age on the orexigenic and lipid metabolism-altering effects of ghrelin. Peripubertal, young, adult and middle-aged rats (1, 2, 7 and 12 months old, respectively) were treated with 5 daily intracerebroventricular injections of ghrelin (0.15 nmol) or saline (control). The food intake was measured daily before treatment, while white adipose tissue and serum/plasma samples for detection of lipid metabolites/hormones were collected at the end of the experiment. The values of cumulative food intake and body weight gain declined, while the white adipose tissue deposits and blood concentrations of triglycerides, cholesterol and free fatty acids all increased with age. Ghrelin significantly increased all parameters, but the stimulatory effects on body weight gain and food intake were more pronounced in peripubertal/young rats, while the increase in white adipose mass, triglyceride and low-density lipoprotein cholesterol levels was more noticeable in adult/middle-aged animals. The decrease in sensitivity to ghrelin-mediated stimulation of food intake in older animals could not be explained by alterations in ghrelin's ability to reduce anorexigenic hormones insulin and leptin. However, the higher responsiveness of aged rats to ghrelin-mediated increase in lipid metabolites was accompanied by an increase in adrenocorticotropic hormone and corticosterone levels. These results indicate that aging, while reducing sensitivity to ghrelin-mediated increase in body weight gain and food intake, might enhance the responsiveness to the stimulatory effects of ghrelin on lipid metabolites and hypothalamic-pituitary-adrenal axis activity. (C) 2013 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats
IS  - 1-3
VL  - 710
SP  - 153
EP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_997
ER  - 

@article{
author = "Nesić, Dejan M and Stevanović, Darko M and Stanković, Sanja Đ and Milošević, Verica and Trajković, Vladimir S and Starčević, Vesna P. and Severs, Walter B",
year = "2013",
abstract = "Ghrelin is an endogenous peptide potentially useful in therapy of anorexia and other age-related metabolic disturbances. We evaluated the influence of age on the orexigenic and lipid metabolism-altering effects of ghrelin. Peripubertal, young, adult and middle-aged rats (1, 2, 7 and 12 months old, respectively) were treated with 5 daily intracerebroventricular injections of ghrelin (0.15 nmol) or saline (control). The food intake was measured daily before treatment, while white adipose tissue and serum/plasma samples for detection of lipid metabolites/hormones were collected at the end of the experiment. The values of cumulative food intake and body weight gain declined, while the white adipose tissue deposits and blood concentrations of triglycerides, cholesterol and free fatty acids all increased with age. Ghrelin significantly increased all parameters, but the stimulatory effects on body weight gain and food intake were more pronounced in peripubertal/young rats, while the increase in white adipose mass, triglyceride and low-density lipoprotein cholesterol levels was more noticeable in adult/middle-aged animals. The decrease in sensitivity to ghrelin-mediated stimulation of food intake in older animals could not be explained by alterations in ghrelin's ability to reduce anorexigenic hormones insulin and leptin. However, the higher responsiveness of aged rats to ghrelin-mediated increase in lipid metabolites was accompanied by an increase in adrenocorticotropic hormone and corticosterone levels. These results indicate that aging, while reducing sensitivity to ghrelin-mediated increase in body weight gain and food intake, might enhance the responsiveness to the stimulatory effects of ghrelin on lipid metabolites and hypothalamic-pituitary-adrenal axis activity. (C) 2013 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats",
number = "1-3",
volume = "710",
pages = "153-91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_997"
}

Nesić, D. M., Stevanović, D. M., Stanković, S. Đ., Milošević, V., Trajković, V. S., Starčević, V. P.,& Severs, W. B.. (2013). Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats. in European Journal of Pharmacology, 710(1-3), 153-91.
https://hdl.handle.net/21.15107/rcub_ibiss_997

Nesić DM, Stevanović DM, Stanković SĐ, Milošević V, Trajković VS, Starčević VP, Severs WB. Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats. in European Journal of Pharmacology. 2013;710(1-3):153-91.
https://hdl.handle.net/21.15107/rcub_ibiss_997 .

Nesić, Dejan M, Stevanović, Darko M, Stanković, Sanja Đ, Milošević, Verica, Trajković, Vladimir S, Starčević, Vesna P., Severs, Walter B, "Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats" in European Journal of Pharmacology, 710, no. 1-3 (2013):153-91,
https://hdl.handle.net/21.15107/rcub_ibiss_997 .

TY  - JOUR
AU  - Milošević, Verica
AU  - Stevanović, Darko M.
AU  - Nešić, Dejan M.
AU  - Šošić-Jurjević, Branka 
AU  - Ajdžanović, Vladimir
AU  - Starčević, Vesna P.
AU  - Severs, Walter B
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1371
AB  - Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 ill phosphate buffered saline with or without 1 mu g of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p < 0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p < 0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p < 0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic disbalance effects, remains a very important research goal.
PB  - Slovak Academy of Sciences
T2  - General Physiology and Biophysics
T1  - Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study
IS  - 2
VL  - 29
DO  - 10.4149/gpb_2010_02_194
SP  - 194
EP  - 202
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1371
ER  - 

@article{
author = "Milošević, Verica and Stevanović, Darko M. and Nešić, Dejan M. and Šošić-Jurjević, Branka  and Ajdžanović, Vladimir and Starčević, Vesna P. and Severs, Walter B",
year = "2010",
abstract = "Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 ill phosphate buffered saline with or without 1 mu g of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p < 0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p < 0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p < 0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic disbalance effects, remains a very important research goal.",
publisher = "Slovak Academy of Sciences",
journal = "General Physiology and Biophysics",
title = "Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study",
number = "2",
volume = "29",
doi = "10.4149/gpb_2010_02_194",
pages = "194-202",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1371"
}

Milošević, V., Stevanović, D. M., Nešić, D. M., Šošić-Jurjević, B., Ajdžanović, V., Starčević, V. P.,& Severs, W. B.. (2010). Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study. in General Physiology and Biophysics
Slovak Academy of Sciences., 29(2), 194-202.
https://doi.org/10.4149/gpb_2010_02_194
https://hdl.handle.net/21.15107/rcub_ibiss_1371

Milošević V, Stevanović DM, Nešić DM, Šošić-Jurjević B, Ajdžanović V, Starčević VP, Severs WB. Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study. in General Physiology and Biophysics. 2010;29(2):194-202.
doi:10.4149/gpb_2010_02_194
https://hdl.handle.net/21.15107/rcub_ibiss_1371 .

Milošević, Verica, Stevanović, Darko M., Nešić, Dejan M., Šošić-Jurjević, Branka , Ajdžanović, Vladimir, Starčević, Vesna P., Severs, Walter B, "Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study" in General Physiology and Biophysics, 29, no. 2 (2010):194-202,
https://doi.org/10.4149/gpb_2010_02_194 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1371 .

TY  - JOUR
AU  - Stevanović, Darko M
AU  - Nesić, Dejan M
AU  - Milošević, Verica
AU  - Starčević, Vesna P.
AU  - Severs, Walter B
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1535
AB  - Ghrelin, an endogenous ligand for the growth-hormone-secretagogue receptor, is a 28-amino acid peptide with a post-translational acyl modification necessary for its activity. It has central nervous system actions that affect appetite, body mass and energy balance. An intracerebroventricular (ICV) injection protocol of sub-nanomolar doses of ghrelin, known to alter the morphology of ACTH and GH producing pituicytes and plasma levels of these hormones, was used to provide an overview of metabolic changes linked to energy metabolism. Variables measured were: food intake (FI), water intake (WI), fecal mass, urine volume, body weight (BW), retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT), and changes in serum leptin, insulin, triglycerides, cholesterol, and glucose. Five injections of rat ghrelin or PBS (n=8 per group) were given ICV every 24 h (1 mu g/5 mu L PBS) to adult male rats. Ghrelin had a positive and cumulative effect on FI, WI and BW (p<0.05), but not feces mass or urine volume (p>0.05). Centrally applied ghrelin clearly increased RP WAT (by 235%, p<0.001), EPI WAT (by 85%, p<0.05) and serum insulin levels (by 43%, p<0.05), and decreased serum leptin levels (by 77%, p<0.05) without (p>0.05) evoking changes in blood triglyceride cholesterol, or glucose levels. These data and the available literature clearly document that exposure of the brain of normal rats, over time, to sub-nanomolar doses of ghrelin results in metabolic dysregulation culminating in increased body mass, consummatory behavior, and lipid stores as well as changes in blood leptin/insulin levels. Thus, modulation of central ghrelin receptors may represent a pharmacological approach for controlling multiple factors involved in energy balance and obesity. (C) 2008 Elsevier B.V. All rights reserved.
T2  - Regulatory Peptides
T1  - Consummatory behavior and metabolic indicators after central ghrelin injections in rats
IS  - 1-3
VL  - 147
EP  - 59
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1535
ER  - 

@article{
author = "Stevanović, Darko M and Nesić, Dejan M and Milošević, Verica and Starčević, Vesna P. and Severs, Walter B",
year = "2008",
abstract = "Ghrelin, an endogenous ligand for the growth-hormone-secretagogue receptor, is a 28-amino acid peptide with a post-translational acyl modification necessary for its activity. It has central nervous system actions that affect appetite, body mass and energy balance. An intracerebroventricular (ICV) injection protocol of sub-nanomolar doses of ghrelin, known to alter the morphology of ACTH and GH producing pituicytes and plasma levels of these hormones, was used to provide an overview of metabolic changes linked to energy metabolism. Variables measured were: food intake (FI), water intake (WI), fecal mass, urine volume, body weight (BW), retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT), and changes in serum leptin, insulin, triglycerides, cholesterol, and glucose. Five injections of rat ghrelin or PBS (n=8 per group) were given ICV every 24 h (1 mu g/5 mu L PBS) to adult male rats. Ghrelin had a positive and cumulative effect on FI, WI and BW (p<0.05), but not feces mass or urine volume (p>0.05). Centrally applied ghrelin clearly increased RP WAT (by 235%, p<0.001), EPI WAT (by 85%, p<0.05) and serum insulin levels (by 43%, p<0.05), and decreased serum leptin levels (by 77%, p<0.05) without (p>0.05) evoking changes in blood triglyceride cholesterol, or glucose levels. These data and the available literature clearly document that exposure of the brain of normal rats, over time, to sub-nanomolar doses of ghrelin results in metabolic dysregulation culminating in increased body mass, consummatory behavior, and lipid stores as well as changes in blood leptin/insulin levels. Thus, modulation of central ghrelin receptors may represent a pharmacological approach for controlling multiple factors involved in energy balance and obesity. (C) 2008 Elsevier B.V. All rights reserved.",
journal = "Regulatory Peptides",
title = "Consummatory behavior and metabolic indicators after central ghrelin injections in rats",
number = "1-3",
volume = "147",
pages = "59",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1535"
}

Stevanović, D. M., Nesić, D. M., Milošević, V., Starčević, V. P.,& Severs, W. B.. (2008). Consummatory behavior and metabolic indicators after central ghrelin injections in rats. in Regulatory Peptides, 147(1-3).
https://hdl.handle.net/21.15107/rcub_ibiss_1535

Stevanović DM, Nesić DM, Milošević V, Starčević VP, Severs WB. Consummatory behavior and metabolic indicators after central ghrelin injections in rats. in Regulatory Peptides. 2008;147(1-3):null-59.
https://hdl.handle.net/21.15107/rcub_ibiss_1535 .

Stevanović, Darko M, Nesić, Dejan M, Milošević, Verica, Starčević, Vesna P., Severs, Walter B, "Consummatory behavior and metabolic indicators after central ghrelin injections in rats" in Regulatory Peptides, 147, no. 1-3 (2008),
https://hdl.handle.net/21.15107/rcub_ibiss_1535 .

TY  - JOUR
AU  - Stevanović, Darko M
AU  - Milošević, Verica
AU  - Starčević, Vesna P.
AU  - Severs, Walter B
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1610
AB  - Ghrelin is a brain-gut peptide known for its growth hormone (GH)-releasing and appetite-inducing activities. This natural GH secretagogue (GHS) was originally purified from rat stomach, but it is expressed widely in different tissues where it may have endocrine and paracrine effects. The central effects of ghrelin on adrenocorticotropic, hormone (ACTH) cells, ACTH release and subsequent corticosterone release from adrenal glands remains to be clarified. The aim of this study was to specifically determine the morphological features of ACTH-producing pituicytes and blood concentration of ACTH and corticosterone after central administration of ghrelin. Five doses of rat ghrelin or PBS (n = 10 per group) were injected every 24 h (1 mu g of ghrelin in 5 mu L PBS), into the lateral cerebral ventricle of male rats. Results showed that ghrelin increased (p < 0.05) absolute and relative pituitary weights compared to controls (58% and 41% respectively). Morphometric parameters, i.e. the volume of the ACTH cells, nuclear volume, and volume density were all increased (p < 0.05), by 17%, 6% and 13%, respectively, 2 h after the last ghrelin treatment. Ghrelin increased circulating concentrations of ACTH and corticosterone (p < 0.05) by 62% and 66%, respectively. The data provide clear documentation that intracerebroventricular ghrelin stimulates ACTH cell hypertrophy and proliferation, and promotes ACTH and corticosterone release. Determining the role of ghrelin in physiological stress responses and whether control of the peptide's activity would be useful for prevention and/or treatment of stress-induced diseases remain important research goals. (c) 2006 Elsevier Inc. All rights reserved.
T2  - Life Sciences
T1  - The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats
IS  - 9
VL  - 80
EP  - 872
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1610
ER  - 

@article{
author = "Stevanović, Darko M and Milošević, Verica and Starčević, Vesna P. and Severs, Walter B",
year = "2007",
abstract = "Ghrelin is a brain-gut peptide known for its growth hormone (GH)-releasing and appetite-inducing activities. This natural GH secretagogue (GHS) was originally purified from rat stomach, but it is expressed widely in different tissues where it may have endocrine and paracrine effects. The central effects of ghrelin on adrenocorticotropic, hormone (ACTH) cells, ACTH release and subsequent corticosterone release from adrenal glands remains to be clarified. The aim of this study was to specifically determine the morphological features of ACTH-producing pituicytes and blood concentration of ACTH and corticosterone after central administration of ghrelin. Five doses of rat ghrelin or PBS (n = 10 per group) were injected every 24 h (1 mu g of ghrelin in 5 mu L PBS), into the lateral cerebral ventricle of male rats. Results showed that ghrelin increased (p < 0.05) absolute and relative pituitary weights compared to controls (58% and 41% respectively). Morphometric parameters, i.e. the volume of the ACTH cells, nuclear volume, and volume density were all increased (p < 0.05), by 17%, 6% and 13%, respectively, 2 h after the last ghrelin treatment. Ghrelin increased circulating concentrations of ACTH and corticosterone (p < 0.05) by 62% and 66%, respectively. The data provide clear documentation that intracerebroventricular ghrelin stimulates ACTH cell hypertrophy and proliferation, and promotes ACTH and corticosterone release. Determining the role of ghrelin in physiological stress responses and whether control of the peptide's activity would be useful for prevention and/or treatment of stress-induced diseases remain important research goals. (c) 2006 Elsevier Inc. All rights reserved.",
journal = "Life Sciences",
title = "The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats",
number = "9",
volume = "80",
pages = "872",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1610"
}

Stevanović, D. M., Milošević, V., Starčević, V. P.,& Severs, W. B.. (2007). The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats. in Life Sciences, 80(9).
https://hdl.handle.net/21.15107/rcub_ibiss_1610

Stevanović DM, Milošević V, Starčević VP, Severs WB. The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats. in Life Sciences. 2007;80(9):null-872.
https://hdl.handle.net/21.15107/rcub_ibiss_1610 .

Stevanović, Darko M, Milošević, Verica, Starčević, Vesna P., Severs, Walter B, "The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats" in Life Sciences, 80, no. 9 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1610 .

TY  - JOUR
AU  - Stevanović, Darko M
AU  - Milošević, Verica
AU  - Nesić, Dejan M
AU  - Ajdžanović, Vladimir
AU  - Starčević, Vesna P.
AU  - Severs, Walter B
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1629
AB  - Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from rat stomach; subsequently, ghrelin neurons were found in the arcuate nuclei of rats. Central effects of the peptide on GH release, however, remain to be clarified. The aim of the present study was to determine the morphologic features of GH-producing pituicytes and serum GH concentration after central administration of ghrelin. Five injections of rat ghrelin or phosphate-buffered saline (PBS; n = 10 rats/group) were given every 24 hrs (1 mu g of ghrelin in 5 mu l of PBS) into the lateral cerebral ventricle of male rats. Significant (P < 0.05) increases in absolute and relative pituitary weights occurred in ghrelin-treated rats versus controls (58% and 41%, respectively). Morphometric parameters (i.e., the volume of GH cells, volume of their nuclei, and volume density) all significantly (P < 0.05) increased by 17%, 18%, and 19%, respectively, in the ghrelin-treated group versus controls. Terminal serum concentration of GH was significantly (P < 0.05) increased by 15% with ghrelin treatment. The results clearly document that daily nanomolar doses of ghrelin into the lateral cerebral ventricle stimulate GH cell proliferation and promote GH release. Thus, achieving pharmacologic control of central ghrelin receptors is a promising modality to modulate the actions of GH.
T2  - Experimental Biology and Medicine
T1  - Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats
IS  - 10
VL  - 231
EP  - 1615
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1629
ER  - 

@article{
author = "Stevanović, Darko M and Milošević, Verica and Nesić, Dejan M and Ajdžanović, Vladimir and Starčević, Vesna P. and Severs, Walter B",
year = "2006",
abstract = "Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from rat stomach; subsequently, ghrelin neurons were found in the arcuate nuclei of rats. Central effects of the peptide on GH release, however, remain to be clarified. The aim of the present study was to determine the morphologic features of GH-producing pituicytes and serum GH concentration after central administration of ghrelin. Five injections of rat ghrelin or phosphate-buffered saline (PBS; n = 10 rats/group) were given every 24 hrs (1 mu g of ghrelin in 5 mu l of PBS) into the lateral cerebral ventricle of male rats. Significant (P < 0.05) increases in absolute and relative pituitary weights occurred in ghrelin-treated rats versus controls (58% and 41%, respectively). Morphometric parameters (i.e., the volume of GH cells, volume of their nuclei, and volume density) all significantly (P < 0.05) increased by 17%, 18%, and 19%, respectively, in the ghrelin-treated group versus controls. Terminal serum concentration of GH was significantly (P < 0.05) increased by 15% with ghrelin treatment. The results clearly document that daily nanomolar doses of ghrelin into the lateral cerebral ventricle stimulate GH cell proliferation and promote GH release. Thus, achieving pharmacologic control of central ghrelin receptors is a promising modality to modulate the actions of GH.",
journal = "Experimental Biology and Medicine",
title = "Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats",
number = "10",
volume = "231",
pages = "1615",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1629"
}

Stevanović, D. M., Milošević, V., Nesić, D. M., Ajdžanović, V., Starčević, V. P.,& Severs, W. B.. (2006). Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats. in Experimental Biology and Medicine, 231(10).
https://hdl.handle.net/21.15107/rcub_ibiss_1629

Stevanović DM, Milošević V, Nesić DM, Ajdžanović V, Starčević VP, Severs WB. Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats. in Experimental Biology and Medicine. 2006;231(10):null-1615.
https://hdl.handle.net/21.15107/rcub_ibiss_1629 .

Stevanović, Darko M, Milošević, Verica, Nesić, Dejan M, Ajdžanović, Vladimir, Starčević, Vesna P., Severs, Walter B, "Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats" in Experimental Biology and Medicine, 231, no. 10 (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1629 .

TY  - JOUR
AU  - Starcević, Vladan
AU  - Milošević, Verica
AU  - Brkić, B
AU  - Severs, Walter B
PY  - 2002
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1797
AB  - The somatostatin peptides (SRIH-14, SRIH-28) and their multiple receptors are generally associated with anti-proliferative and anti-secretory actions. This study compared, using standard morphometric measurements and terminal serum LH concentrations, effects of intracerebroventricular (icv) SRIH-14 and SFIH-28 in nanomolar amounts on immunohistochemically identified LH cells in pituitary glands of male rats. Rats received I mug/5 mul of SRIH-14 or SRIH-28 icv on days 1,3, and 5, whereas control rats received only icv saline. Animals were killed 5 days later for serum LH assays. Pituitarys were harvested for PAP immunohistochemistry and morphometry. Morphometric measurements were made by an observer blinded to the treatment group. Histochemically identified LH cells from both SRIH groups appeared smaller, often pycnotic and darkly stained compared to those from saline-treated rats. Both SRIH treatments reduced (p < 0.05) the quantitative morphometric measurements for cell volume, nuclear volume, and relative volume density. Both SRIH treatments also reduced serum LH concentration (p < 0.05), supporting the hypothesis that systemic physiology was altered. Collectively, the data support the opinion that nanomolar amounts of either SRIH peptide, acting on receptors reached from cerebrospinal fluid, exert an anti-secretory effect on LH cells of male rats. Modifications of central SRIH receptors may provide an approach for treatment of male sexual dysfunction and/or be of pathophysiologic significance in these disturbances. (C) 2002 Elsevier Science Inc. All fights reserved.
T2  - Life Sciences
T1  - Somatostatin affects morphology and secretion of pituitary luteinizing hormone (LH) cells in male rats
IS  - 25
VL  - 70
EP  - 3027
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1797
ER  - 

@article{
author = "Starcević, Vladan and Milošević, Verica and Brkić, B and Severs, Walter B",
year = "2002",
abstract = "The somatostatin peptides (SRIH-14, SRIH-28) and their multiple receptors are generally associated with anti-proliferative and anti-secretory actions. This study compared, using standard morphometric measurements and terminal serum LH concentrations, effects of intracerebroventricular (icv) SRIH-14 and SFIH-28 in nanomolar amounts on immunohistochemically identified LH cells in pituitary glands of male rats. Rats received I mug/5 mul of SRIH-14 or SRIH-28 icv on days 1,3, and 5, whereas control rats received only icv saline. Animals were killed 5 days later for serum LH assays. Pituitarys were harvested for PAP immunohistochemistry and morphometry. Morphometric measurements were made by an observer blinded to the treatment group. Histochemically identified LH cells from both SRIH groups appeared smaller, often pycnotic and darkly stained compared to those from saline-treated rats. Both SRIH treatments reduced (p < 0.05) the quantitative morphometric measurements for cell volume, nuclear volume, and relative volume density. Both SRIH treatments also reduced serum LH concentration (p < 0.05), supporting the hypothesis that systemic physiology was altered. Collectively, the data support the opinion that nanomolar amounts of either SRIH peptide, acting on receptors reached from cerebrospinal fluid, exert an anti-secretory effect on LH cells of male rats. Modifications of central SRIH receptors may provide an approach for treatment of male sexual dysfunction and/or be of pathophysiologic significance in these disturbances. (C) 2002 Elsevier Science Inc. All fights reserved.",
journal = "Life Sciences",
title = "Somatostatin affects morphology and secretion of pituitary luteinizing hormone (LH) cells in male rats",
number = "25",
volume = "70",
pages = "3027",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1797"
}

Starcević, V., Milošević, V., Brkić, B.,& Severs, W. B.. (2002). Somatostatin affects morphology and secretion of pituitary luteinizing hormone (LH) cells in male rats. in Life Sciences, 70(25).
https://hdl.handle.net/21.15107/rcub_ibiss_1797

Starcević V, Milošević V, Brkić B, Severs WB. Somatostatin affects morphology and secretion of pituitary luteinizing hormone (LH) cells in male rats. in Life Sciences. 2002;70(25):null-3027.
https://hdl.handle.net/21.15107/rcub_ibiss_1797 .

Starcević, Vladan, Milošević, Verica, Brkić, B, Severs, Walter B, "Somatostatin affects morphology and secretion of pituitary luteinizing hormone (LH) cells in male rats" in Life Sciences, 70, no. 25 (2002),
https://hdl.handle.net/21.15107/rcub_ibiss_1797 .

TY  - JOUR
AU  - Starcević, Vladan
AU  - Milošević, Verica
AU  - Brkić, B
AU  - Severs, Walter B
PY  - 2000
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1839
AB  - Effects of intracerebroventricular (i.c.v.) application of somatostatin (SRIH-14 or SRIH-28) on growth and function of pituitary adrenocorticotropes (ACTH cells) were examined in adult female Wistar rats. Animals were subjected to i.c.v. administration of three 1-mu g doses of SRIH-14 or SRIH-28 dissolved in 5 mu l saline every second day, Controls were treated in the same way with the same volume of saline only, ACTH-producing cells were studied using the peroxidase-anti peroxidase (PAP) immunohistochemical procedure; blood samples were collected for hormone analyses 5 days after the last injection, SRIH-28 treatment decreased (p < 0.05) all morphometric parameters compared to control rats. Volume of ACTH cells decreased by 10%, nuclei by 36% and volume density by 13%, No significant changes (p > 0.05) in these para meters occurred after SRIH-14 treatment. Plasma concentration of ACTH in SRIH-28-treated rats was significantly lower (p < 0.05) than in control rats by 35%. In SRIH-14-treated rats, plasma concentration of ACTH was slightly, but not significantly (p > 0.05) increased by 13% compared to saline treatment. These observations suggest that centrally administered somatostatin-28, but not somatostatin-14, is specifically involved in the control of growth and secretory activity of ACTH cells in female rats, Thus, selective pharmacological manipulation of SRIH-28 receptors reached from CSF may affect ACTH activity without altering actions usually attributed to receptors sensitive to SRIF-14. Copyright (C) 2000 S. Karger AG, Basel.
T2  - Pharmacology
T1  - Effects of centrally applied somatostatin on pituitary adrenocorticotropes in female rats
IS  - 4
VL  - 60
EP  - 207
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1839
ER  - 

@article{
author = "Starcević, Vladan and Milošević, Verica and Brkić, B and Severs, Walter B",
year = "2000",
abstract = "Effects of intracerebroventricular (i.c.v.) application of somatostatin (SRIH-14 or SRIH-28) on growth and function of pituitary adrenocorticotropes (ACTH cells) were examined in adult female Wistar rats. Animals were subjected to i.c.v. administration of three 1-mu g doses of SRIH-14 or SRIH-28 dissolved in 5 mu l saline every second day, Controls were treated in the same way with the same volume of saline only, ACTH-producing cells were studied using the peroxidase-anti peroxidase (PAP) immunohistochemical procedure; blood samples were collected for hormone analyses 5 days after the last injection, SRIH-28 treatment decreased (p < 0.05) all morphometric parameters compared to control rats. Volume of ACTH cells decreased by 10%, nuclei by 36% and volume density by 13%, No significant changes (p > 0.05) in these para meters occurred after SRIH-14 treatment. Plasma concentration of ACTH in SRIH-28-treated rats was significantly lower (p < 0.05) than in control rats by 35%. In SRIH-14-treated rats, plasma concentration of ACTH was slightly, but not significantly (p > 0.05) increased by 13% compared to saline treatment. These observations suggest that centrally administered somatostatin-28, but not somatostatin-14, is specifically involved in the control of growth and secretory activity of ACTH cells in female rats, Thus, selective pharmacological manipulation of SRIH-28 receptors reached from CSF may affect ACTH activity without altering actions usually attributed to receptors sensitive to SRIF-14. Copyright (C) 2000 S. Karger AG, Basel.",
journal = "Pharmacology",
title = "Effects of centrally applied somatostatin on pituitary adrenocorticotropes in female rats",
number = "4",
volume = "60",
pages = "207",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1839"
}

Starcević, V., Milošević, V., Brkić, B.,& Severs, W. B.. (2000). Effects of centrally applied somatostatin on pituitary adrenocorticotropes in female rats. in Pharmacology, 60(4).
https://hdl.handle.net/21.15107/rcub_ibiss_1839

Starcević V, Milošević V, Brkić B, Severs WB. Effects of centrally applied somatostatin on pituitary adrenocorticotropes in female rats. in Pharmacology. 2000;60(4):null-207.
https://hdl.handle.net/21.15107/rcub_ibiss_1839 .

Starcević, Vladan, Milošević, Verica, Brkić, B, Severs, Walter B, "Effects of centrally applied somatostatin on pituitary adrenocorticotropes in female rats" in Pharmacology, 60, no. 4 (2000),
https://hdl.handle.net/21.15107/rcub_ibiss_1839 .

TY  - JOUR
AU  - Milošević, Verica
AU  - Brkić, B
AU  - Velkovski, SD
AU  - Sekulić, Milka I.
AU  - Lovren, Mirjana B.
AU  - Starcević, V
AU  - Severs, Walter B
PY  - 1998
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1859
AB  - This study examined effects of intracerebroventricularly (i.c.v.) administered somatostatin (SRIH-14 and SRIH-28) on growth and function of pituitary somatotropes (GH cells) and lactotropes (PRL cells), Male rats received three i.c.v. injections (1 mu g/5 mu l) of SRIH-14 or SRIH-28 every second day, Blood samples were collected for hormone assays and pituitaries were removed for histological and morphometric evaluation 5 days after the last i.c.v. treatment, Compared to control animals, SRIH treatment decreased (p < 0.05) pituitary weight and all morphometric measurements obtained in GH and PRL cells, Concentrations of serum growth hormone (GH) and prolactin (PRL) in both SRIH-treated groups were also lower (p < 0.05) than in control rats, These findings suggest that centrally administered somatostatin is specifically involved in the control of growth and secretory activity of GH and PRL cells, Thus, pharmacological manipulation of SRIH receptors reached from cerebrospinal fluid may alter systemic effects of GH and PRL.
T2  - Pharmacology
T1  - Morphometric and functional changes of rat pituitary somatotropes and lactotropes after central administration of somatostatin
IS  - 1
VL  - 57
EP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1859
ER  - 

@article{
author = "Milošević, Verica and Brkić, B and Velkovski, SD and Sekulić, Milka I. and Lovren, Mirjana B. and Starcević, V and Severs, Walter B",
year = "1998",
abstract = "This study examined effects of intracerebroventricularly (i.c.v.) administered somatostatin (SRIH-14 and SRIH-28) on growth and function of pituitary somatotropes (GH cells) and lactotropes (PRL cells), Male rats received three i.c.v. injections (1 mu g/5 mu l) of SRIH-14 or SRIH-28 every second day, Blood samples were collected for hormone assays and pituitaries were removed for histological and morphometric evaluation 5 days after the last i.c.v. treatment, Compared to control animals, SRIH treatment decreased (p < 0.05) pituitary weight and all morphometric measurements obtained in GH and PRL cells, Concentrations of serum growth hormone (GH) and prolactin (PRL) in both SRIH-treated groups were also lower (p < 0.05) than in control rats, These findings suggest that centrally administered somatostatin is specifically involved in the control of growth and secretory activity of GH and PRL cells, Thus, pharmacological manipulation of SRIH receptors reached from cerebrospinal fluid may alter systemic effects of GH and PRL.",
journal = "Pharmacology",
title = "Morphometric and functional changes of rat pituitary somatotropes and lactotropes after central administration of somatostatin",
number = "1",
volume = "57",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1859"
}

Milošević, V., Brkić, B., Velkovski, S., Sekulić, M. I., Lovren, M. B., Starcević, V.,& Severs, W. B.. (1998). Morphometric and functional changes of rat pituitary somatotropes and lactotropes after central administration of somatostatin. in Pharmacology, 57(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1859

Milošević V, Brkić B, Velkovski S, Sekulić MI, Lovren MB, Starcević V, Severs WB. Morphometric and functional changes of rat pituitary somatotropes and lactotropes after central administration of somatostatin. in Pharmacology. 1998;57(1):null-34.
https://hdl.handle.net/21.15107/rcub_ibiss_1859 .

Milošević, Verica, Brkić, B, Velkovski, SD, Sekulić, Milka I., Lovren, Mirjana B., Starcević, V, Severs, Walter B, "Morphometric and functional changes of rat pituitary somatotropes and lactotropes after central administration of somatostatin" in Pharmacology, 57, no. 1 (1998),
https://hdl.handle.net/21.15107/rcub_ibiss_1859 .