Abstract 245: Role Of Melanocortin-4-receptor In The Blood Pressure Regulation In Female Hyperandrogenemic Rats, A Model Of Polycystic Ovary Syndrome

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Roberta Lima ◽  
Jussara M do Carmo ◽  
Alexander Da Silva ◽  
John E Hall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Food Intake ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Sprague Dawley ◽  
Ovary Syndrome ◽  
Melanocortin 4 Receptor ◽  
Ad Libitum

Women with polycystic ovary syndrome (PCOS) are characterized by hyperandrogenemia, hirsutism, infertility, and enlarged cystic ovaries. Obesity and hypertension are also frequently found in women with PCOS, although the mechanisms responsible for the elevated blood pressure (BP) are unclear. Thus we tested the hypothesis that the melanocortin-4 receptor (MC4R), known to contribute to obesity hypertension in males, contributes to the elevated BP in hyperandrogenemic female rats, a model of PCOS. Female Sprague Dawley rats (4 wks) were implanted with dihydrotestosterone (DHT; 7.5mg/90 days sc) or placebo pellets (PL) (n=5/grp) and aged to 12 wks. Body weight and food intake (whether rats were pair fed or had ad libitum access) were measured daily. Two wks following implantation of radiotelemetry transmitters and intracerebroventricular cannulae, baseline mean arterial pressure (MAP) was measured for 5 days; then rats received MC3/4R antagonist, SHU-9119 (SHU; 1 nmol/h ICV) or vehicle for 7 days and MAP was recorded. DHT-treated rats had higher body weight and MAP than PL rats (BW: PL: 266.0±8.7; DHT: 348.5±10.4 g, p<0.01; MAP: PL rats: 102±5; DHT: 114±5 mmHg, p<0.05). SHU significantly increased food intake and body weights in both placebo (PL) and DHT-treated rats fed ad libitum (PL: 379.2±28.5; DHT: 451/3±7.3 g, p<0.01 DHT vs PL; 0.01 SHU vs control), but had no effect on MAP compared to controls (PL: 104±5; HAF rats: 114±5 mmHg; p<0.05, HAF vs PL; p=NS, SHU vs controls). However, in other rats, when pair fed with little increase in body weight (PL: 253.7±2.0, SHU: 261.0±0.6, p<0.05; DHT: 306.7±2.6, SHU: 316.7±1.5 g, p<0.05), SHU decreased MAP in DHT treated rats but not placebo controls (PL rats: 102±1, SHU: 103±2 mmHg; p=NS; DHT rats: 110±1 vs. SHU: 97±1 mmHg; p<0.001). Thus MC4R antagonist reduces MAP in DHT-treated rats only when food intake and body weight are controlled. These data suggest that activation of MC4R contributes to elevated BP in our model of PCOS and may also contribute to the elevated BP in women with PCOS. Supported by NIH R01HL66072, P01HL05971 and AHA 14POST18640015.

scholarly journals Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

2020 ◽  
Author(s):  
Zahra Shaaban ◽  
Amin Tamadon ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Amin Derakhshanfar
Keyword(s):  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Body Weight Gain ◽  
Late Pregnancy ◽  
Female Offspring ◽  
Female Rats ◽  
Sprague Dawley ◽  
Ovary Syndrome ◽  
Letrozole Treatment

Abstract Background: Despite the prevalence of polycystic ovary syndrome (PCOS) among childbearing women and the development of many animal models for this syndrome, information on its etiology is still scarce. Intrauterine hyperandrogenic environment may underlie changes at the levels of hypothalamus, pituitary and ovary organization in female offspring, and PCOS later in life. Letrozole, has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, the aim of this research was to assess the condition in a prenatal letrozole-treated rat model. Methods: Twenty-eight female rats from dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on days 16-18 gestation at doses 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW).Results: Prenatal letrozole-treatment delayed parturition time and reduced the litter size in pregnant dams (P<0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, and serum testosterone concentration and reduced estradiol levels (P<0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, Letrozole at 1.25 and 1 mg/kg BW showed increased Rfrp and decreased Gnrh mRNA expression (P<0.0001). Conclusions: Letrozole treatment at doses 1 mg/kg BW and lower was not feto-toxic. It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.

scholarly journals Effect of Metformin Therapy on Clinical and Hormonal Indices of Patients with Polycystic Ovary Syndrome

2021 ◽  
Vol 15 (5) ◽  
pp. 1522-1525
Author(s):  
S. Inayat ◽  
H. F. Khattak ◽  
M. G. Muhammad ◽  
K. Robeen ◽  
A. Inayat ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Blood Sugar ◽  
Body Mass ◽  
Polycystic Ovary ◽  
Fasting Blood Sugar ◽  
Ovary Syndrome ◽  
Group Ii

Objective: The main objective of this study is to determine the efficacy of metformin therapy on clinical and hormonal indices of patients with polycystic ovary syndrome. Study Design: Randomized control trial Place and Duration: Study was conducted at Obstetrics & Gynaecology department of Northwest General Hospital and Research Center, Peshawar and Mian Rashid Hussain Shaheed Memorial Hospital, Pabbi for duration of nine months from March 2020 to November 2020. Methods: Total 100 patients of polycystic ovary syndrome were presented in this study. Patients were aged between 18 to 45years. Patients detailed demographics including age, body mass index and socio-economicstatus were recorded after taking informed written consent. Patients were divided into 2-groups, group I had 50 patients and received metformin (500 mg) three times a day and group II had 50 patients and received pioglitazone (30 mg) three times a day for 3months.Clinical (body weight, blood pressure (BP), and body mass index) and indices fasting blood sugar (FBS), serum triglyceride (TG), cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone (DHEA) were measured before and after therapy. Complete data was analyzed by SPSS 22.0 version. Results: Mean age of the patients in group I was 29.18 ± 2.25 years with mean BMI 26.14 ± 8.86 kg/m2 and in group II mean age was 29.8 ± 2.52 years with mean BMI 27.64 ± 7.68 kg/m2.Significantly decrease in blood pressure (systolic 105.41±8.57, diastolic 67.19±8.9), hair loss 20 (40%),oligomenorrhea 23 (46%), body weight 74.45±9.72, waist circumference and dehydroepiandrosterone (DHEA) 2.35±0.67 and as compared to group II. Only triglycerides gave results of reduction in group II 115.39±64.11. Among both groups serum insulin, acne, menstrual disturbance and fasting blood sugar were controlled after treatment. Conclusion: We concluded in this study that use of metformin in patients with polycystic ovary syndrome resulted in to decrease clinical body weight, blood pressure (BP), body mass index and hormonal indices with reduction of serum insulin, acne, menstrual disturbance and fasting blood sugar but pioglitazone was an alternative effective and reliable method in PCOS patients. Keywords: Polycystic ovary syndrome, Insulin resistance, Metformin, Pioglitazone

Abstract 246: Role Of Cytochrome P450 4a2 In Mediating The Elevated Blood Pressure In A Rat Model Of Polycystic Ovary Syndrome

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Chetan N Patil ◽  
Carolina Dalmasso ◽  
Richard Roman ◽  
Jane F Reckelhoff
Keyword(s):  
Blood Pressure ◽  
Cytochrome P450 ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Renal Vasculature ◽  
Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) often have elevated blood pressure (BP). PCOS is characterized in part by increases in androgens, and androgens can increase cytochrome P450 (CYP) 4A isoforms and 20-HETE synthesis. We have found that CYP4A2 expression is increased in renal vasculature of hyperandrogenemic female rats, a model of PCOS. In the present study we tested the hypothesis that androgen increase would not cause elevated BP in CYP4A2 -/- rats compared with wild type SS.Bn5 rats. CYP4A2 -/- and SS.Bn5 rats (n=6-8/grp) were treated from 4 wks of age with dihydrotestosterone pellets (DHT 7.5 mg/90 d) or placebo pellets until 14 wks, and then telemetry transmitters were implanted. After 2 wks, mean arterial pressure (MAP) was measured for 10 days. DHT increased MAP and decreased HR in SS.Bn5 compared with placebo controls (placebo: 104±2 vs. DHT: 126±6 mmHg, p<0.001). In contrast, while placebo-treated CYP4A2 -/- rats had higher MAP than WT, DHT did not increase BP in CYP4A2 -/- rats (Placebo: 120±1 vs. DHT: 118±1 mmHg, p=NS). These data suggest that CYP4A2 may be necessary for DHT to increase BP in our model of PCOS. However, by what mechanism(s) CYP4A2 -/- rats have higher MAP than SS.Bn5 WT remains to be determined. Supported by NIH R01HL66072, P01HL05971 and AHA 14POST18640015.

scholarly journals Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model

2015 ◽  
Vol 308 (12) ◽  
pp. E1076-E1084 ◽  
Author(s):  
Ilana B. Ressler ◽  
Bernadette E. Grayson ◽  
Yvonne M. Ulrich-Lai ◽  
Randy J. Seeley
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Forced Swim Test ◽  
Rodent Model ◽  
Reproductive Age ◽  
Female Rats ◽  
Ovary Syndrome ◽  
Stress Responsivity

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.

scholarly journals Pregnancy Protects Hyperandrogenemic Female Rats From Postmenopausal Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 943-952
Author(s):  
Noha M. Shawky ◽  
Chetan N. Patil ◽  
Carolina Dalmasso ◽  
Rodrigo O. Maranon ◽  
Damian G. Romero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Female Rats ◽  
Ovary Syndrome ◽  
Uncomplicated Pregnancy ◽  
Age Related ◽  
Endothelin B

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.

scholarly journals Normalizing of estrous cycle in polycystic ovary syndrome (PCOS) induced rats with Tephrosia purpurea (Linn.) Pers.

2014 ◽  
Vol 6 (1) ◽  
pp. 197-201 ◽  
Author(s):  
Akanksha P. Thakor ◽  
Anuradha J. Patel
Keyword(s):  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Alternative Therapy ◽  
Good Alternative ◽  
Female Rats ◽  
Plasma Testosterone ◽  
Vaginal Smear ◽  
Ovary Syndrome ◽  
Tephrosia Purpurea

This study evaluates the potentiality of an herbal plant Tephrosia purpurea (Linn.) Pers. in the treatment of Letrozole induced polycystic ovary syndrome (PCOS) using female Albino wistar rats. Seed powder of T. purpurea at concentration of 200 mg/kg body weight with milk as a carrier vehicle 3ml/kg body weight, given for at least 3 consecutive estrous cycles. Vaginal smear, FSH, LH, Testosterone, and Estrogen were analyzed to determine the fluctuations in sex steroid level in PCOS induced rats. The plasma testosterone and estrogen levelwere found to be significantly increased in rats with PCOS whereas Follicle stimulating hormone and Leutinizing hormone did not show any changes. When compared with control the PCOS induced rats showed characteristic ovary with high incidence of ovarian cyst. All the parameters assessed were significantly improved after the treatment with T. purpurea and achieved level close to 80% normalcy. Effect of T. purpurea significantly reduced histopathological changes in ovary and endocrinological and biochemical changes induced by hyperandrogenism. Further to check ovulation and fertility female rats were mated and pregnancy was confirmed. Thus potential of T. purpurea in the treatment of PCOS using an animal model suggested being a good alternative therapy in the treatment of PCOS.

Evaluation of hunger sensation, ad libitum food intake, and ghrelin postprandial response in obese women with and without polycystic ovary syndrome

2013 ◽  
Vol 100 (3) ◽  
pp. S334
Author(s):  
M.F. Silva-de-Sá ◽  
C.C. Japur ◽  
F.R.O. Penaforte ◽  
R.W. Diez-Garcia
Keyword(s):  
Food Intake ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Postprandial Response ◽  
Ad Libitum ◽  
Hunger Sensation

scholarly journals Enhancement of Melanocortin-4 Receptor (MC4R) and Constancy of Kiss1 mRNAs Expression in the Hypothalamic Arcuate Nucleus in a Model of Polycystic Ovary Syndrome Rat

2018 ◽  
Vol 7 ◽  
pp. e1070
Author(s):  
Mohammad Hossein Nooranizadeh ◽  
Farhad Rahmanifar ◽  
Somayeh Ahmadloo ◽  
Zahra Shaaban ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Arcuate Nucleus ◽  
Polycystic Ovary ◽  
Continuous Light ◽  
Female Rats ◽  
Ovary Syndrome ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
And Control

Background: Hypothalamic Melanocortin-4 Receptor (MC4R) and kiss1/kisspeptin systems play roles in reproductive processes. This study was conducted to evaluate changes in MC4R and kiss1 genes expression in the arcuate nucleus (ARC) of the hypothalamus and its relationship with polycystic ovary syndrome (PCOS) in rats.Materials and Methods: In the current experimental study, 24 female rats were randomly and equally allocated into nulliparous and primiparous groups and then were divided into two subgroups of PCOS and control. PCOS was induced by exposure to continuous light. Sex-related hormones were evaluated by radioimmunoassay or immunoradiometric assay. Expressions of MC4R and kiss1 gene in the ARC of the hypothalamus of the rats were evaluated by real-time PCR. Histomorphometric alterations of ovaries were compared between groups.Results: Number of tertiary follicles and their size and number of atretic follicles in the PCOS subgroups were more than those in the controls (P<0.05) whereas the number of secondary follicles and corpus luteum in the PCOS subgroups were lower than those in the controls (P<0.05). Antrum and total diameters of tertiary follicles in the PCOS subgroups were greater and granulosa layer diameter was lower than those in the controls (P<0.05). The MC4R mRNA expression in the PCOS subgroups was 6.5-fold in nulliparous and 3.5-fold in primiparous groups more than their controls’ pairs (P<0.05). However, parity did not affect the expression of MC4R gene (P>0.05).The kiss1 mRNA expression in the PCOS and control subgroups was not significantly different (P>0.05).Conclusion: Overexpression of MC4R gene after PCOS induction in the ARC of the hypothalamus may link to metabolic disorders of induced PCOS in the rats. However, alteration in the kiss1 mRNA expression after PCOS induction was not observed in the rats. [GMJ.2018;7:e1070]

scholarly journals Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4071-4080 ◽  
Author(s):  
Amanda Hurliman ◽  
Jennifer Keller Brown ◽  
Nicole Maille ◽  
Maurizio Mandala ◽  
Peter Casson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Phase 1 ◽  
Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

Exenatide Reduces Body Weight but Not Hyperandrogenemia in Overweight Women with Polycystic Ovary Syndrome

2011 ◽  
pp. P2-242-P2-242
Author(s):  
Alison J Dawson ◽  
Thozhukat Sathyapalan ◽  
Eric S Kilpatrick ◽  
Stephen L Atkin
Keyword(s):  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Overweight Women
Sign in / Sign up

Export Citation Format

Share Document