10 research outputs found
Dihydrotestosterone deteriorates cardiac insulin signaling and glucose transport in the rat model of polycystic ovary syndrome
It is supposed that women with polycystic ovary syndrome (PCOS) are
prone to develop cardiovascular disease as a consequence of multiple
risk factors that are mostly related to the state of insulin resistance
and consequent hyperinsulinemia. In the present study, we evaluated
insulin signaling and glucose transporters (GLUT) in cardiac cells of
dihydrotestosterone (DHT) treated female rats as an animal model of
PCOS. Expression of proteins involved in cardiac insulin signaling
pathways and glucose transporters, as well as their phosphorylation or
intracellular localization were studied by Western blot analysis in
DHT-treated and control rats. Treatment with DHT resulted in increased
body mass, absolute mass of the heart, elevated plasma insulin
concentration, dyslipidemia and insulin resistance. At the molecular
level, DHT treatment did not change protein expression of cardiac
insulin receptor and insulin receptor substrate 1, while phosphorylation
of the substrate at serine 307 was increased. Unexpectedly, although
expression of downstream Akt kinase and its phosphorylation at threonine
308 were not altered, phosphoiylation of Akt at serine 473 was increased
in the heart of DHT-treated rats. In contrast, expression and
phosphorylation of extracellular signal regulated kinases 1/2 were
decreased. Plasma membrane contents of GLUT1 and GLUT4 were decreased,
as well as the expression of GLUT4 in cardiac cells at the end of
androgen treatment. The obtained results provide evidence for
alterations in expression and especially in functional characteristics
of insulin signaling molecules and glucose transporters in the heart of
DHT-treated rats with PCOS, indicating impaired cardiac insulin action.
(c) 2014 Elsevier Ltd. All rights reserved.Ministry of Education, Science and Technological Development, Republic
of Serbia {[}III41009
Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is associated with an altered plasma
lipid profile and increased risk for cardiovascular diseases. We
hypothesized that molecular mechanisms underlying cardiac pathology in
PCOS involve changes in expression and subcellular localization of
several key proteins involved in cardiac lipid transport and metabolism,
such as fatty acid transporter CD36, lipin 1, peroxisome
proliferator-activated receptor alpha (PPAR alpha), peroxisome
proliferator-activated receptor gamma coactivator-1 (PGC1), and
carnitine palmitoyltransferase 1 (CPT1). We used the animal model of
PCOS obtained by treating female rats with dihydrotestosterone (DHT).
Protein levels of CD36, lipin 1, PPAR alpha, PGC1, and antioxidative
enzymes were assessed by Western blot in different cardiac cell
compartments. Cardiac triglycerides (TG) and lipid peroxidation were
also measured. The content of CD36 was decreased in both the cardiac
plasma membranes and intracellular pool. On the other hand, total
content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast
to decreased microsomal lipin 1 content. An increase in nuclear content
of lipin 1 was observed together with elevation of nuclear PPAR alpha
and PGC1, and an increase in CPT1 expression. However, lipid
peroxidation was reduced in the heart, without alterations in
antioxidative enzymes expression and cardiac TG content. The results
indicate that treatment of female rats with DHT is accompanied by a
decrease of fatty acid uptake and a reduction of lipid peroxidation in
the heart. The observed elevation of lipin 1, PPAR alpha, PGC1, and CPT1
expression suggests that cardiac fatty acid metabolism is shifted toward
mitochondrial beta oxidation.Ministry of Education, Science and Technological Development, Republic
of Serbia {[}III41009
The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome
OBJECTIVE: Most women with PCOS have increased adrenal androgen
production, enhanced peripheral metabolism of cortisol and elevation in
urinary excretion of its metabolites. Increased cortisol clearance in
PCOS is followed by a compensatory overdrive of the
hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that
oral contraceptives containing ethinylestradiol and drospirenone
(EE-DRSP) could modulate glucocorticoid receptor (GR) expression and
function and thus affect HPA axis activity in PCOS patients. DESIGN: We
analyzed 12 women with PCOS (age 24.17 +/- 4.88 years; body mass index
22.05 +/- 3.97 kg/m(2)) treated for 12 months with EE-DRSP and 20 BMI
matched controls. In all subjects testosterone, dehydroepiandrosterone
sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal
and after dexamethasone), concentrations of GR protein, phospo-GR211
protein, number of GR per cell (B-max) and its equilibrium dissociation
constant (K-D) were measured. RESULTS: Before treatment, increased
concentrations of testosterone and DHEAS (p<0.001, respectively),
unaltered basal cortisol and an increased sensitivity (p<0.05) of the
HPA axis to dexamethasone were observed in PCOS women in comparison to
controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and
cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS
women. There were no changes in GR protein concentration, GR
phosphorylation nor in the receptor functional parameters B-max and K-D
in women with PCOS before and after the therapy, and in comparison to
controls. CONCLUSIONS: Prolonged treatment with EE-DRSP in PCOS women
decreased serum androgens and increased cortisol in the presence of
decreased sensitivity of the HPA axis and did not exert changes in GR
expression and function.Ministry of Education, Science and Technological Development of the
Republic of Serbia {[}11141009
The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome
OBJECTIVE: Most women with PCOS have increased adrenal androgen
production, enhanced peripheral metabolism of cortisol and elevation in
urinary excretion of its metabolites. Increased cortisol clearance in
PCOS is followed by a compensatory overdrive of the
hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that
oral contraceptives containing ethinylestradiol and drospirenone
(EE-DRSP) could modulate glucocorticoid receptor (GR) expression and
function and thus affect HPA axis activity in PCOS patients. DESIGN: We
analyzed 12 women with PCOS (age 24.17 +/- 4.88 years; body mass index
22.05 +/- 3.97 kg/m(2)) treated for 12 months with EE-DRSP and 20 BMI
matched controls. In all subjects testosterone, dehydroepiandrosterone
sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal
and after dexamethasone), concentrations of GR protein, phospo-GR211
protein, number of GR per cell (B-max) and its equilibrium dissociation
constant (K-D) were measured. RESULTS: Before treatment, increased
concentrations of testosterone and DHEAS (p<0.001, respectively),
unaltered basal cortisol and an increased sensitivity (p<0.05) of the
HPA axis to dexamethasone were observed in PCOS women in comparison to
controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and
cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS
women. There were no changes in GR protein concentration, GR
phosphorylation nor in the receptor functional parameters B-max and K-D
in women with PCOS before and after the therapy, and in comparison to
controls. CONCLUSIONS: Prolonged treatment with EE-DRSP in PCOS women
decreased serum androgens and increased cortisol in the presence of
decreased sensitivity of the HPA axis and did not exert changes in GR
expression and function.Ministry of Education, Science and Technological Development of the
Republic of Serbia {[}11141009