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


CONCLUSIONS
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.
Vedrana
V
Ivić
Senka
S
Blažetić
Irena
I
Labak
Marta
M
Balog
Luka
L
Vondrak
Robert
R
Blažeković
Sandor G
SG
Vari
Marija Heffer, Department of Medical Biology and Genetics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 10/E, HR-31000 Osijek, Croatia, mheffer@mefos.hr.
Marija
M
Heffer
D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000378:metabolism; D013315:Stress, Psychological
D020738:Leptin; D054411:Receptors, Leptin