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]

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 Association between Luteinizing Hormone/Choriogonadotropin Receptor Ins18LQ Gene Polymorphism and Polycystic Ovary Syndrome

2020 ◽  
Vol 8 (A) ◽  
pp. 517-520
Author(s):  
Hilma Putri Lubis ◽  
Muhammad Fidel Ganis Siregar ◽  
Ichwanul Adenin ◽  
Binarwan Halim ◽  
Henry Salim Siregar ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Polycystic Ovary Syndrome ◽  
Gene Polymorphism ◽  
Polycystic Ovary ◽  
Control Group ◽  
Control Groups ◽  
Ovary Syndrome ◽  
Significant Difference ◽  
Pcos Group ◽  
And Control

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of women in the childbearing period. However, its pathophysiology is still unclear. Certain polymorphisms of the luteinizing hormone/choriogonadotropin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. The important functional role of LHCGR in the metabolism of androgen and ovulation, the LHCGR gene variant, may be related to the risk of PCOS. AIM: The aim of this study was to evaluate the association between LHCGR Ins18LQ gene polymorphism and PCOS. METHODS: A case–control study was performed in women with PCOS and non-PCOS from May 2019 to October 2019 in HFC IVF Center. We included 50 women with PCOS and 50 healthy controls. Polymorphism of the LHCGR (ins18LQ) gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: From this study, we found that there was no significant difference in the proportion of ages between the groups (p > 0.05). There were significant differences in the characteristics of body mass index, FSH level, LH level, and LH/FSH ratio between the PCOS and control groups (p < 0.05). We also found that the proportion of heterozygote variant non-ins/ins was higher in the PCOS group compared to the control group, but there was no significant difference between the polymorphisms of the non-ins and non-nonins variants between the PCOS and control groups (p = 0.269). The frequency of ins alleles was higher in the PCOS group compared to the control group. CONCLUSION: There was no significant association between LHCGR ins18LQ gene polymorphism and PCOS.

scholarly journals Androgen Receptor Blocker Improves the Cardiometabolic Profile in a Rat Model of Polycystic Ovary Syndrome, but at What Cost?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A803-A804
Author(s):  
Jacob E Pruett ◽  
Steven Everman ◽  
Edgar David Torres Fernandez ◽  
Kacey Davenport ◽  
Damian G Romero ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Female Rats ◽  
Chow Diet ◽  
Model Assessment ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Glutamyl Transferase ◽  
Cardiometabolic Profile

Abstract Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by androgen excess and ovulatory dysfunction high prevalence of cardiovascular risk factors such as increased blood pressure (BP), insulin resistance (IR), and obesity. We have demonstrated previously that exposing prepubertal female rats to dihydrotestosterone (DHT) leads to increase in food intake (FI), body weight (BW), BP, and IR. We tested the hypothesis that administration of the AR blocker bicalutamide (BICA) would decrease BP, IR, and obesity in PCOS model. As there are previous reports of severe hepatotoxicity with the AR blocker flutamide, we also examined BICA effects in the liver. Methods: Four-week old female Sprague Dawley rats implanted with DHT pellets (7.5mg/90 days) or placebo (PBO) were randomized to standard chow diet with or without the AR blocker bicalutamide (BICA) at a dose of 250 mg/kg/day throughout the study (n=10/group). BW and FI were measured weekly. BP and heart rate (HR) were measured by radiotelemetry. Fasting plasma was collected for IR (Homeostatic model assessment for IR, HOMA-IR). At euthanasia, the liver was collected, as well as plasma for gamma glutamyl transferase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) quantification. Results: PCOS rats had increased BW, FI, IR, and BP compared to PBO. BICA treatment had no impact on BW (285.3 ± 7.0 vs 270 ± 8.2 g, P=0.2) as well as FI and HR in PCOS. However, in PCOS, BICA decreased HOMA-IR (5.10 ± 0.40 vs 3.33 ± 0.31, P&lt;0.05) and BP (115.4 ± 0.7 vs 105.3 ± 0.2 mmHg, P&lt;0.01). Compared to PBO, PCOS+BICA rats had similar IR (3.83 ± 0.28 vs 3.33 ± 0.31, P=0.7) and BP (107.4 ± 0.8 vs 105.3 ± 0.2 mmHg, P=0.9). In addition, the liver weight to tibia length ratio was drastically increased by BICA in PCOS (222.9 ± 9.5 vs 360.4 ± 16.9 mg/mm, P&lt;0.0001) as well as GGT (0.88 ± 0.88 vs 11.67 ± 0.58 U/L, P&lt;0.0001), though it decreased AST (60.2 ± 6.9 vs 42.4 ± 1.9 U/L, P&lt;0.05) and had no impact on ALT. Conclusion: In summary, in a model of PCOS, BICA treatment abolished IR and BP, independent of FI, BW and HR. Prompt treatment with an AR blocker can normalize increased IR and BP triggered by androgen excess in females. Further studies need to be done to fully understand the effect of BICA in the liver in PCOS. The beneficial effect of AR blockers as a therapeutic option to improve the cardiometabolic profile in PCOS may be hampered by its liver toxicity.

Dietary diversity score is inversely related to the risk of polycystic ovary syndrome in Tehranian women: a case-control study

2021 ◽  
pp. 1-6
Author(s):  
Sahel Soodi ◽  
Seyed Ali Keshavarz ◽  
Sedighe Hosseini ◽  
Behnood Abbasi
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Case Control Study ◽  
Dietary Diversity ◽  
Polycystic Ovary ◽  
Case Control ◽  
Control Groups ◽  
Ovary Syndrome ◽  
And Control ◽  
The Relationship ◽  
Control Study

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is affected by various dietary factors. Therefore, this study aimed to investigate the relationship between dietary diversity score (DDS) and the risk of PCOS. Our case-control study was conducted in the summer and autumn of 2019 in Taleghani and Arash hospitals in Tehran, Iran. A total of 494 participants (203 cases and 291 controls) were included in the study. Thereafter, their demographic information, dietary intake, and anthropometric and physical activity assessments were gathered. A validated semi-quantitative food frequency questionnaire was then used to calculate the DDS by scoring 5 food groups. To evaluate the risk of PCOS in association with DDS, the subjects were categorized based on the quartile cut-off points of the DDS. The mean ± SD age of the participants in both the case and control groups was 28.98 ± 5.43 and 30.15 ± 6.21 years, while mean ± SD body mass index was 25.74 ± 5.44 and 23.65 ± 3.90 kg/m2, respectively. The comparison between the case and control groups indicated that total DDS was 5.19 ± 1.19 for the cases and 5.51 ± 1.19 for the controls. The comparison of DDS in the highest versus the lowest quartiles showed a decreased risk of PCOS (p < 0.05). We demonstrated an inverse association between DDS and PCOS compared with the control group. Furthermore, a higher DDS was significantly associated with a lower risk of PCOS (odds ratio = 0.40). Novelty: This is the first investigation on the relationship between DDS and PCOS. Results depicted an inverse relationship between DDS and PCOS.

scholarly journals Letrozole-Induced Polycystic Ovary Syndrome Attenuates Cystathionine-β Synthase Gene Expression in the Ovaries of Female Sprague Dawley Rats

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1244-1244
Author(s):  
Amanda Bries ◽  
Joe Webb ◽  
Brooke Vogel ◽  
Claudia Carrillo ◽  
Aileen Keating ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Reproductive Age ◽  
Sprague Dawley ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Sd Rats

Abstract Objectives Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 10% of reproductive age women and leads to hyperandrogenism, abnormal menstrual cycles, and polycystic ovaries. Moreover, PCOS has been associated with elevated serum homocysteine; however, the characterization of one-carbon metabolism (OCM) in PCOS remains incomplete. The aim of our research was to examine OCM in a genetic and chemically-induced rodent model of PCOS: 1) viable yellow Agouti (Avy) mice; and 2) letrozole (Let)-induced Sprague Dawley (SD) rats. Methods Five wk old female Avy mice (N = 18), their lean controls (N = 18), and SD rats (N = 36) were acclimated for one wk. Following acclimation, the animals were placed on a modified standard AIN93G diet (energy, %: 50.4, carbohydrate; 17.3, protein; and 32.3, fat). Rats were randomly assigned to Let (1 g/kg BW) treatment or vehicle (carboxymethylcellulose) control that was administered via a subcutaneously implanted slow-release pellet every 30-d. For both models, 12 animals were randomly assigned to be euthanized during proestrus at one of the following ages: 8, 16 or 24 wk. Bodyweight and estrous cycles were measured daily. Ovaries were collected to assess gene expression of OCM. These data were analyzed using linear mixed models to determine the main effects of age and treatment at a significance level of P &lt; 0.05. Results Letrozole significantly reduced the occurrence of proestrus and estrus stages (P = 0.0001 and P = 0.006, respectively). Additionally, Let-induced rats had increased BW compared to control rats, across all age groups (P &lt; 0.0001). In contrast, Avy mice weighed less than their controls by 24 wk of age (P &lt; 0.0001). Cystathionine-β synthase (CBS) mRNA expression was downregulated in the Let-induced vs. control rats at 16 (59%; P &lt; 0.05) and 24 (77%; P &lt; 0.01) wk of age. As expected, Cyp19A1, aromatase mRNA was downregulated in the Let-induced rats (P = 0.02). Interestingly, betaine-homocysteine s-methyltransferase (BHMT) mRNA increased as a function of age in Let-induced rats (P = 0.03). Conclusions These data demonstrate that Letrozole-induced PCOS temporally decreases ovarian CBS mRNA expression; whereas, BHMT mRNA is upregulated as a function of age. Funding Sources This work was supported by the National Institute of Child Health and Human Development.

Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome

2010 ◽  
Vol 299 (4) ◽  
pp. E551-E559 ◽  
Author(s):  
Julia Johansson ◽  
Yi Feng ◽  
Ruijin Shao ◽  
Malin Lönn ◽  
Håkan Billig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Lipid Profile ◽  
Muscle Protein ◽  
Polycystic Ovary ◽  
Low Frequency ◽  
Density Lipoprotein ◽  
Female Rats ◽  
Ovary Syndrome

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20–25 min five times/wk for 4–5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity.

Renal Androgen and Renin Angiotensin System mRNA Expression in Polycystic Ovary Syndrome

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Stephanie A. Ye ◽  
Steven Everman ◽  
Edgar D. Torres Fernandez ◽  
Damian G. Romero ◽  
Licy L. Yanes Cardozo
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Renin Angiotensin System ◽  
Ovary Syndrome ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Serum Leptin Concentrations in Women with Polycystic Ovary Syndrome

1997 ◽  
Vol 82 (6) ◽  
pp. 1697-1700 ◽  
Author(s):  
Juha Rouru ◽  
Leena Anttila ◽  
Pertti Koskinen ◽  
Tuula-Anneli Penttilä ◽  
Kerttu Irjala ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Univariate Analysis ◽  
Serum Triglyceride ◽  
Free Testosterone ◽  
Ovary Syndrome ◽  
Serum Leptin ◽  
Control Subjects ◽  
And Control

Abstract The role of gonadotropins, androgens, and insulin in the regulation of circulating leptin levels is obscure. In order to clarify the relationships of these parameters we studied serum leptin levels in 19 healthy control subjects and in 35 hyperandrogenic and hyperinsulinemic patients with polycystic ovary syndrome (PCOS). Serum leptin concentrations did not differ significantly between PCOS patients and control subjects. When PCOS and control groups were analyzed together by univariate analysis, serum leptin was positively correlated with body mass index (BMI), body weight, serum insulin, serum triglyceride, and serum free testosterone concentrations. Serum leptin was inversely correlated with serum sex hormone binding globulin (SHBG) concentrations. There were no significant correlations between serum leptin and testosterone, androstenedione, or gonadotropin concentrations. Serum insulin, triglyceride, and free testosterone concentrations were positively correlated, and serum SHBG was negatively correlated with BMI. However, when BMI on one hand and serum insulin, triglyceride, free testosterone, or SHBG on other hand were used as independent variables in the partial correlation analysis with leptin, BMI turned out to be the variable primarily responsible for all of the correlations with leptin. In conclusion, the concept that circulating leptin levels would be different in PCOS patients than in regularly menstruating control subjects is not supported by our data.

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