Investigation Trp64Arg polymorphism of the beta 3-adrenergic receptor gene in nonobese women with polycystic ovarian syndrome

Background: Polycystic ovary syndrome (PCOS) is a multifactorial and heterogeneous disease that has a potent inheritable component based on familial clustering. Despite many studies in the genetic field of PCOS, the genes that are involved in the causes of this syndrome have not been thoroughly investigated. Objective: The purpose of this study was to establish the occurrence of the Trp64Arg polymorphism of beta3 adrenergic receptor in non-obese women with PCOS. Materials and Methods: This cross-sectional study was performed on 100 women with PCOS and normal women as the control group in Imam Khomeini Hospital of Tehran in 2016-2017. Peripheral blood sample (2 cc) was obtained from two groups for genomic DNA based on the gene bank. Polymorphisms were genotyped by of using ADRB3 Trp64Arg. Then the DNA was extracted by genomic kiagen kit. The primer was analyzed for PCR based on gene bank by using Primer3 software and then confirmed by primer Blast tool at NCBI site to conformity to the beta-3 adrenergic receptor gene. The protein changes were assessment by the Clastal W software. Results: The sequence analysis presented in NCBI, transcript variant 1, with the code NM_000025.2, shows changes in the amino acid sequence of exon 1 in women with PCOS. Polymorphism in the codon 64 encoding the amino acid tryptophan (W) occurred in the nucleotide c.T190C, which changed the nucleotide T to C and then the amino acid sequence of the tryptophan was altered to arginine pW64R. Conclusion: T-C polymorphism is evident in the codon 64 of the adrenergic β3 receptor in patients with PCOS. Therefore, Beta3 adrenergic receptor gene polymorphism (Thr164Ile) associates with this syndrome in nonobese women. Key words: Codon 64, Beta-3 adrenergic receptor, Polymorphism, Polycystic ovarian syndrome

Stress and the Adolescent Brain: Plasticity of Reproductive Behaviors in Female

Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging.  Much research attention has focused on the programming effects of the hypothalamus pituitary axis (HPA) in early life and on understanding HPA function in response to stressors in adulthood. In comparison, there has been relatively little research on adolescence, a time of significant brain development particularly in the frontal lobe and a time which is of great importance for mental and physical health. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. During adolescence, HPA function is characterized by a prolonged activation in response to stressors compared to adulthood, which may render ongoing development of the brain vulnerable. Stress reactivity is markedly influenced by both the pubertal maturation and the experience of the individual. The frequency of the pulses is increased in chronic stress, since the neuroendocrine system is such a good candidate for mediators of many diseases linked to chronic stress. The activity of HPA axis  in life time of female,  sex maturity, pregnancy or lactation is a plasticity of the diurnal rhythm of pulse amplitude; chronic stress can change this program for   formation disorder in behavioral and physiological responses

Stress and Female Reproductive System: Disruption of Corticotropin-Releasing Hormone/Opiate Balance by Sympathetic Nerve Traffic

Nowadays stress is an integral part of everyday living and the physiological and behavioral consequences of exposure to stressful situations have been extensively studied for decades. The stress response is a necessary mechanism but disrupts homeostatic process and it is sub served by a complex system located in both the central nervous system (CNS) and the periphery. Stressor-induced activation of the hypothalamus–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS) results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Normal activation of the HPA axis is essential for reproduction, growth, metabolic homeostasis, and responses to stress and they are critical for adapting to changes in the external environment. The regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classical feedback mechanisms in the hypothalamus and the pituitary. The present overview focuses on the neuroendocrine infrastructure of the adaptive response to stress and its effects on the female reproductive system.

Chronic Stress and Limbic-Hypothalamopituitary-Adrenal Axis (LHPA) Response in Female Reproductive system

The hypothalamo-pituitary-adrenocortical (HPA) axis is a critical adaptive system that maximizes survival potential in the face of physical or psychological challenge. The principal end products of the HPA axis, glucocorticoid hormones, act on multiple organ systems, including the brain, to maintain homeostatic balance. The brain is a target of stress, and the hippocampus is the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. These anatomical areas in brain are limbic system, and in particular the hippocampus, medial prefrontal cortex (mPFC) and amigdal that have multiple control points in regulation of the hypothalamic–pituitary–adrenal (HPA) axis. The studies show the prefrontal cortex (PFC) plays an important role in the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA) activity and regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classic feedback mechanisms in the hypothalamus and pituitary gland. Chronic stress can have a deleterious effect on the reproductive axis that, for females, is manifested in reduced pulsatile gonadotropin secretion and increased incidence of ovulatory abnormalities and infertility. The limbic–hypothalamic–pituitary–adrenal (LHPA) axis suggests a functional role for gonadal steroids in the regulation of a female’s response to stress

Acute Cold / Restraint Stress in Castrated Rats

Objective: The present study aimed to determine whether castration altered osmotically stimulated vasopressin (VP) release and urinary volume and what is the role of endocrine-stress axis in this process. Materials and methods: Totally 108 mice were studied in two main groups of castrated (n=78) and control (n=30). Each group was extracted by acute cold stress (4◦C for 2h/day), restraint stress (by syringes 60cc 2h/day) and cold/restraint stress. The castrated group was treated in sub groups of testosterone, control (sesame oil as vehicle of testosterone). Propranolol as blocker of sympathetic nervous system was given to both groups of castrated mice and main control. Results: Our results showed that, there is interactions between testosterone and sympathetic nervous system on vasopressin, because urine volume was decreased only in testoctomized mice with cold/restraint and cold stress (P<0.001); propranolol as the antagonist of sympathetic nervous system could block and increase urine volume in castrated mice. This increased volume of urine was due to acute cold stress, not restraint stress (p<0.001). The role of testosterone, noradrenalin (NA) and Vasopressin (VP) in the acute cold stress is confirmed, because testosterone could return the effect of decreased urine volume in control group (P<0.001). Conclusion: Considering the effect of cold/restraint stress on urinary volume in castrated mice shows that there is interaction between sex hormone (testosterone), vasopressin and adrenergic systems

Psychoneuromedulator role of corticotrophin releasing hormone in PCOS

Background: Polycystic ovary syndrome (PCOS) is a common complex condition in women associated with reproductive and metabolic systems and also psychological disorders. There is considerable evidence to suggest that the sympathetic nervous system is involved in PCO and metabolic syndromes. Noradrenalin (NA), corticotrophin releasing hormone (CRH) and nerve growth factor (NGF) are the strong stimulants for two axes: hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-ovarian (HPO) axes which are regulators for the female reproductive system. Following previous studies on sympathetic nervous system over activity in PCOS, the main purpose of this study is to evaluate the role of CRH and NGF as two important findings from the perspective of the psycho-emotional. Methods: This case-control study was conducted in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran, Iran in the September of 2011. 170 women participated in this study. The diagnosis of PCOS was made according to the joint criteria of the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine (ESHRE/ASRM). All women have 20-40 years of age and body mass index (BMI) of less than 28. Demographic questionnaire was used in this study and blood sample was obtained from all participants before 8AM. All analysis was done in SPSS software, version 19 (IBM SPSS, Armonk, NY, USA). P-value less than 0.05 considered as significant level. Results: Serum levels of CRH and NGF in patients with polycystic ovary was significantly lower than the control group (P< 0.001). This reduction can disrupt two neural axes: the sympathetic nervous system (SAS) and hypothalamus-pituitary-adrenal (HPA). These axes have a fundamental role in psycho-emotional reactions in women with PCOS. Moreover, using demographic questionnaire quantitative and qualitative characteristics of the population studied, the results of which are reported in the regression model. Conclusion: The results of this study confirmed previous studies. This reduction in serum levels of CRH and NGF shows the hyperactivity of sympathetic nervous system in polycystic ovary syndrome can be one of the causes of mental disorders in women with PCOS

Comparing life style of patients with polycystic ovary syndrome and normal women

Background: Polycystic ovary syndrome (PCOS) is one of the most common neuroendocrine-metabolic disorders at the infertile age. Patients with PCO often at risk for secondary complications including metabolic difficulties (impaired glucose tolerance, insulin resistance, type 2 diabetes mellitus), reproductive (hirsutism, hypeandrogenism, infertility) and psychological features (worsened quality of life, anxiety, depression). Studies of the past decade suggest that the quality of life is important in the improvement of this syndrome. The purpose of this study was to provide an accurate pattern in the lifestyle of these women. Methods: This case-control study was conducted to assess the lifestyle of patients with polycystic ovary syndrome who referred to Vali-e-Asr Infertile Clinic of Imam Khomeini Hospital, Tehran, from March to February 2015. After filling the consent form, 168 women participated in this study with the age range of 20-40 years and the body mass index (BMI) less than 28 m2/kg. The dimensions of lifestyle in this study were evaluated by the following questionnaires: general qualities of life (GHQ-28), Pittsburgh sleep quality, depression-anxiety-stress (DASS-42) and researcher-made demographic questionnaire. Results: The mean of BMI and weight in study group were higher than control group (P= 0.002) (P< 0.001). Symptoms of PCOS such as irregular cycle (P< 0.001) and hirsutism (P< 0.001) in the study group were greater than the control group. Sleep problems such as drug use (P= 0.048), late sleep (P= 0.024), and sleep adequacy (P= 0.049) were also higher in the study group than control group. Conclusion: These results indicate that environmental factors can easily effect on the quality of life in PCO women. The pattern of sleep is not desirable. Menstrual disorder effects on the mood and the impact of the low income generates negative emotions and affects their quality of life, since the cost of treatment for infertility is high for the low-income families. Therefore, this study indicates that having proper weight and proper sleep can help to plan a correct pattern of lifestyle in these patients

The psychoneuromedulator role of corticotrophin releasing hormone in women with Polycystic Ovary

&nbsp; The psychoneuromedulator role of corticotrophin releasing hormone in women with Polycystic Ovary Farideh Zafari Zangeneh1*, Mohammad Mehdi Naghizadeh2 Masoumeh Masoumi1 Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran Department of Community Medicine, Medical Faculty, Fasa University of Medical Sciences, Fasa, Iran Address: Reproductive Health Research Center, Imam Hospital Complex, Keshavarz Blvd., Tehran, Iran. &nbsp;&nbsp;&nbsp; E-mail: [email protected] Tel. +982166581616 Fax No.: +982166581658 Abstract Background: Polycystic ovary syndrome (PCOS) is a common complex condition in women associated with reproductive and metabolic systems and also psychological disorders. There is considerable evidence to suggest that the sympathetic nervous system is involved in PCO and metabolic syndroms. Noradrenalin (NA), corticotrophin releasing hormone (CRH) and nerve growth factor (NGF) are the strong stimulants for two axes: hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-ovarian (HPO) axes which are regulators for the female reproductive system. Following previous studies on sympathetic nervous system overactivity in PCOS, the main purpose of this study is to evaluate the role of CRH and NGF as two important findings from the perspective of the psycho-emotional. Methods: This case/control study has been down in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran, Iran in 2015. 170 women participated in this study with 20-40 years of age and body mass index (BMI) of less than 28. Data analysis was using by t-tests, Chi-square and Mann Whitney. &nbsp; Results: Serum levels CRH and NGF in patients with polycystic ovary was significantly lower than the control group (p<0.001). This reduction can disrupt two neural axes and the sympathetic nervous system activity and&nbsp; have a&nbsp; fundamental role in psycho-emotional reactions in women with PCOS. Moreover, using demographic questionnaire quantitative and qualitative characteristics of the population studied, the results of which are reported in the regression model. &nbsp; Conclusions: The results of this study confirmed previous studies. This reduction in serum levels of CRH and NGF shows the hyperactivity of sympathetic nervous system in polycystic ovary syndrome can be one of the causes of mental disorders in women with PCOS. &nbsp

Polycystic ovary syndrome and circulating inflammatory markers

Background: Human and experimental studies suggest that the sympathetic regulatory drive in the ovary may be unbalanced (hyperactivity) in polycystic ovary syndrome (PCOS). Dysfunctional secretion of interleukin (IL) -1 (&alpha; & &beta;) or related cytokines may thus be related to abnormal ovulation and luteinization. Objective: The aim of this study was the evaluation of cytokines&rsquo; pattern in PCOS women and discussion about the explanation of cross-talk between two super systems: sympathetic and immune systems and explanation sympatho-excitation and relationship with interleukins. Materials and Methods: In this study, 171 PCOS women aged between 20-40 years were studied. Their body mass index was <28. The patients were divided into two groups: study group (n=85, PCOS women) and control group (n=86 normal women). The blood sample was obtained on the 3rd day of menstruation cycle. IL-17, IL-1&alpha;, IL-1&beta;, and Tumor necrosis factor-alpha (TNF-&alpha;) concentrations were determined in both groups. Results: The median serum level of IL-1&alpha; in the PCOS group was higher than the control group (293.3 and 8.0, respectively, p<0.001). Also, the median serum level of IL-1&beta; was higher than the control group (5.9 and 3.1 respectively). But the median serum of level IL-17 in women with PCOS was significantly lower than the control group (p<0.001). Conclusion: Our results confirm that PCOS is a low-level chronic inflammatio

Locus coeruleus lesion & cold stress: Role of the central and peripheral sympathetic nervous system in rat’s late proestrous phase

Objective: LC/NA system is activator of hypothalamic–pituitar–adrenal (HPA) axis and cold stress triggers an equally robust increase in plasma NA. Increased LHRH content probably due to absence or decrease of NE release from the LC and positive feedback action of E2 on LH secretion show that in late proestrous phase NA, LH and E2 have a strong link. This study was conducted to evaluate the effect of central sympathetic nervous system (by LC lesion and acute cold stress induction) and peripheral sympathetic nervous system (with propranolol administration) on late proestrous phase in rat. Material and Method: One hundred eight rats were divided into control and study groups. Study group was divided into three main sub groups: LC lesion (electrolytic lesion), acute cold stress (4°C for 20 minutes) and propranolol (antagonist of sympathetic nervous system). Vaginal smears were taken for all groups and late proestrous was selective phase for this study. Statistical differences were determined by one–way ANOVA followed by the Tukey post hoc test. SPSS 11 was used for data analysis. P value ≤ 0.05 was defined as significant level. Results: LC lesion decreased only estradiol level (P≤0.001) but could increase serum level of LH like propranolol administration (7mg/kg ip) (P≤0.01). No significant changes were noted in the levels of LH and estradiol in cold stress group like the synergistic effect of LC lesion and Cold stress also synergism of LC lesion, Cold stress and propranolol. Conclusion: This study demonstrated that late proestrous phase has a critical role in LH surge and sympathetic nervous system (NA) and E2 are important and basic factors in this process