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Croatian Medical Journal, Vol. 57 No. 2, 2016.

Original scientific paper

https://doi.org/10.3325/cmj.2016.57.194

Ovariectomy and chronic stress lead toward leptin resistance in the satiety centers and insulin resistance in the hippocampus of Sprague- Dawley rats

Vedrana Ivić ; Josip Juraj Strossmayer University of Osijek, Faculty of MedicineOsijek, Department of MedicalBiology and Genetics, Osijek, Croatia
Senka Blažetić ; Josip Juraj Strossmayer University of Osijek, Department of Biology, Osijek, Croatia
Marta Balog ; Josip Juraj Strossmayer University of Osijek, Faculty of MedicineOsijek, Department of MedicalBiology and Genetics, Osijek, Croatia
Luka Vondrak ; Josip Juraj Strossmayer University of Osijek, Department of Biology, Osijek, Croatia
Robert Blažeković ; Department of Cardiac and Transplantation Surgery, UniversityHospital Dubrava, Zagreb, Croatia
Sandor G. Vari ; International Research and Innovation in Medicine Program,Cedars–Sinai Medical Center, LosAngeles, CA, USA
Marija Heffer orcid id orcid.org/0000-0001-6770-7359 ; Josip Juraj Strossmayer University of Osijek, Faculty of MedicineOsijek, Department of MedicalBiology and Genetics, Osijek, Croatia

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Abstract

Aim To evaluate the changes in the expression level of
gonadal steroid, insulin, and leptin receptors in the brain
of adult Sprague-Dawley female rats due to ovariectomy
and/or chronic stress.
Methods Sixteen-week-old ovariectomized and non-ovariectomized
female Sprague-Dawley rats were divided in
two groups and exposed to three 10-day-sessions of sham
or chronic stress. After the last stress-session the brains
were collected and free-floating immunohistochemical
staining was performed using androgen (AR), progesterone
(PR), estrogen-β (ER-β), insulin (IR-α), and leptin receptor
(ObR) antibodies. The level of receptors expression was
analyzed in hypothalamic (HTH), cortical (CTX), dopaminergic
(VTA/SNC), and hippocampal regions (HIPP).
Results Ovariectomy downregulated AR in the hypothalamic
satiety centers and hippocampus. It prevented or
attenuated the stress-specific upregulation of AR in these
regions. The main difference in stress response between
non-ovariectomized and ovariectomized females was in
PR level. Ovariectomized ones had increased PR level in the
HTH, VTA, and HIPP. Combination of stressors pushed the
hypothalamic satiety centers toward the rise of ObR and
susceptibility to leptin resistance. When exposed to combined
stressors, the HIPP, SNC and piriform cortex upregulated
the expression of IR-α and the possibility to develop
insulin resistance.
Conclusion Ovariectomy exacerbates the effect of chronic
stress by preventing gonadal receptor-specific stress response
reflected in the up-regulation of AR in the satiety
and hippocampal regions, while stress after ovariectomy
usually raises PR. The final outcome of inadequate stress
response is reflected in the upregulation of ObR in the satiety
centers and IR-α in the regions susceptible to early
neurodegeneration. We discussed the possibility of stress
induced metabolic changes under conditions of hormone
deprivation

Keywords

Hrčak ID:

169586

URI

https://hrcak.srce.hr/169586

Publication date:

15.4.2016.

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