Kisspeptin and polycystic ovary syndrome - is there any connection?

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is known that kisspeptin stimulates activity of GnRH neurons and secretion of FSH and LH, thus disruption of interaction between kisspeptin and its receptor leads to anovulation. The aim of the study was to investigate the role kisspeptin in the pathogenesis of polycystic ovary syndrome. Materials and methods. The study included 14 patients with classic phenotype of PCOS and 11 healthy women of the control group. All the patients underwent laparoscopy and hysteroscopy with histological examination of ovarian tissue and endometrium. Determination of kisspeptin, FSH, LH, prolactin, AMH, estradiol, estrone, androgens (free testosterone and dehydroepiandrosterone sulfate) levels in peripheral blood in healthy women and patients with PCOS was performed by ELISA on the 2d and 8th days of menstrual cycle. Progesterone levels were investigated on the 18th-22d days of menstrual cycle. Expression of kisspeptin and its receptor in ovarian tissue and endometrium was estimated using immunohistochemical method. Results. Level of kisspeptin in peripheral blood of patients with PCOS tends to increase compared to its level in the control group, but the found difference was not reliable. Direct correlation between serum level of kisspeptin and levels of LH, free testosterone and DHEA-S was revealed in patients with PCOS. Immunohistochemical study in patients with PCOS showed a significant increase in the area of expression of КІЅЅ1 and KISS1R receptor in endometrium and in ovarian biopsies compared to these values in the control group. Conclusion. The obtained data show a definite role of kisspeptin in pathogenesis of polycystic ovary syndrome, but further research is needed.

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The role of metastin in pathogenesis of genital endometriosis

Journal of obstetrics and women s diseases ◽

10.17816/jowd66316-24 ◽

2017 ◽

Vol 66 (3) ◽

pp. 16-24 ◽

Cited By ~ 1

Author(s):

Edvard K. Aylamazyan ◽

Mariya I. Yarmolinskaya ◽

Nigar F. Ganbarli ◽

Natalia N. Tkachenko ◽

Gulrukhsor Kh. Tolibova ◽

...

Keyword(s):

Menstrual Cycle ◽

Histological Examination ◽

Peripheral Blood ◽

Ovarian Tissue ◽

Free Testosterone ◽

Immunohistochemical Method ◽

Control Group ◽

Healthy Women ◽

Definition Of

Materials and methods. 28 patients with GE of I-II degrees of prevalence (R-AFS) were included in the study. Control group consisted of 11 healthy women. All the patients underwent laparoscopy and hysteroscopy with histological examination of ovarian tissue, peritoneum and endometrium; patients with GE also were performed histological examination of endometrioid of heterotopies. Definition of levels of kisspeptin, FSH, LH, prolactin, AMH, estradiol, estrone, androgens (free testosterone, dehydroepiandrosterone – DHEA) in peripheral blood in healthy women and in patients with GE were conducted by ELISA on the 2nd and 8th days of menstrual cycle. Immunohistochemical method was used to evaluate expression of metastine (kisspeptin) and its receptor in ovarian tissue, peritoneum, in endometrioid heterotopies and in endometrium. Results. Hormonal survey has revealed that the level of kisspeptin in peripheral blood was reliably higher compared to its level in the control group. Immunohistochemical study found that in patients with GE area of expression of KISS and KISS1R receptor in endometrium was reliably lower when compared with these values in the control group. In the foci of endometrioid heterotopies, which were located on the pelvic peritoneum, it was observed a reliable increase in protein КІЅЅ1 expression and receptor KISS1R compared to fragments of intact peritoneum. The area of expression of receptor KISS1R in endometrioid heterotopies was reliably higher than the area of its expression in endometrium of patients with GE and in endometrium of women of the control group. Direct correlation between the area of protein expression (KISS) in endometrium with level kisspeptin on the 8th day of menstrual cycle in peripheral blood (rs = 0,90) has been revealed. It has been determined that the level of kisspeptin on the 2nd day of menstrual cycle in peripheral blood correlates with the area of expression of receptor KISS1R in peritoneum (rs = 0,57). A direct correlation between the area of expression of receptor KISS1R in peritoneum with the level of kisspeptin on the 8th day of menstrual cycle in serum has been found (rs = 0,90). Conclusion. The obtained data show a definite role of kisspeptin in pathogenesis of genital endometriosis. It can be assumed that the increase in the level of metastine (kisspeptin) in peripheral blood and increased expression of KISS1 in endometrioid heterotopies and especially its receptor KISS1R are compensatory-adaptive response aimed at deterrence of further spread of endometriosis. The obtained results justify the need to continue research in this direction for a deeper understanding of pathogenesis of the disease and possible use of kisspeptin as biomarker for non-invasive diagnostics as well as potential targeted therapy of GE.

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Evaluation the levels of some hormones in women with polycystic ovary syndrome

Tikrit Journal of Pure Science ◽

10.25130/j.v24i5.862 ◽

2019 ◽

Vol 24 (5) ◽

pp. 25

Author(s):

Namareq Ata allah Mohemeed1 ◽

Firas Shawki Abdul-razzak2

Keyword(s):

Menstrual Cycle ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Follicle Stimulating Hormone ◽

Control Group ◽

Age Group ◽

Ovary Syndrome ◽

Blood Samples ◽

Healthy Women ◽

Stimulating Hormone

This study was conducted on 40 Samples of Patients with polycystic ovary syndrome (PCOS) after their diagnosis, The study aimed to identify the most important hormonal disorders associated with this syndrome . The study begins from Octobar 2017 to March 2018 , the age from(19-45) years .Blood samples were taken during the (2-4( days of menstrual cycle and the selected samples were compared with 20 healthy women as control group ,and the following hormones were evaluated Luteninzing hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL),Testosterone (Testo) and Oxytocin (OX) ,the study showed a high significant in the concentrations of OX ,Testo and LH (P≤0.01) , a high significant in the PRL concentration (P≤0.05) and a high significant in the FSH concentration (P≤0.05(,the results were distributed to three groups according to BMI ,age and treatment, in term BMI it was divided into three groups, BMI(18.5-24.9)(25.0-29.9) (≥30)kg/m2 the results showed a high significant (P≤0.05) in the LH and OX concentration in group BMI (18.5-24.9)kg/m2 and in both PRL and Testo in group BMI(≥30)kg/m2. in term age, it was divided into three groups (19-26) (27-35) (36-45)years, the results showed a high significant (P≤0.05) in LH and Testo concentration at age group (36-45)years ,compared to other groups, and a high significant (P≤0.05) in both PRL and OX, between three group of age , treatment it was divided into three groups of metformin, progesterone contraceptive used and non-used of the treatment .the results showed a high significant (P≤0.05) in LH, PRL, OX and Testo concentrations, and a high significant (P≤0.05) of FSH in women treated compared with non-used . http://dx.doi.org/10.25130/tjps.24.2019.085

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Serum inhibin B in polycystic ovary syndrome as a potential marker of ovarian dysfunction

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0808379c ◽

2008 ◽

Vol 136 (7-8) ◽

pp. 379-383

Author(s):

Aleksandar Cetkovic

Keyword(s):

Menstrual Cycle ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Inhibin B ◽

Control Group ◽

Serum Concentrations ◽

Ovarian Dysfunction ◽

Ovary Syndrome ◽

The Third ◽

Healthy Women

INTRODUCTION Polycystic ovary syndrome (PCOS) is one of the most common causes of anovulation, infertility and hyperandrogenism, and the prevalence of this condition in women of reproductive is 5-10%. The growth of early ovarian antral follicles is arrested and dominant follicle selection is disturbed in this syndrome. OBJECTIVE The aim of this study is to investigate whether inhibin B serum concentrations represent the extent of ovarian abnormalities in patients with PCOS. METHOD Inhibin B serum concentrations on the third day of spontaneous menstrual cycle and other endocrine characteristics were compared between 20 patients with PCOS and 19 healthy women in the control group. RESULTS Inhibin B concentrations were not significantly different between women with PCOS and women in the control group. In patients with PCOS there was statistically significant correlation between serum inhibin B and LH (r=0.514; p=0.021). There were no positive correlations between inhibin B and others endocrine parameters in patients with PCOS (FSH, E2, T, androstenedione). CONCLUSION Inhibin B serum concentrations on the third day of spontaneous menstrual cycle in women with PCOS are not different from the concentrations in healthy women. Serum Inhibin B levels in patients with PCOS are only slightly correlated with the endocrine markers of the disease so it could not represent the magnitude of ovarian dysfunction in this syndrome.

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Abnormal expression of uncoupling protein-2 correlates with CYP11A1 expression in polycystic ovary syndrome

Reproduction Fertility and Development ◽

10.1071/rd10266 ◽

2011 ◽

Vol 23 (4) ◽

pp. 520 ◽

Cited By ~ 12

Author(s):

Yun Liu ◽

Hong Jiang ◽

Ling-Yun He ◽

Wu-Jian Huang ◽

Xiao-Yu He ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Early Stage ◽

Uncoupling Protein ◽

Serum Insulin ◽

Ovarian Tissue ◽

Fasting Blood Glucose ◽

Control Group ◽

Ovary Syndrome ◽

Protein Levels

Polycystic ovary syndrome (PCOS) may result from hypersensitivity to insulin, which is negatively regulated by uncoupling protein (UCP)-2. Because cholesterol side-chain cleavage enzyme (CYP11A1) is closely linked to PCOS, the expression of UCP-2 and CYP11A1 in ovarian tissues from PCOS patients was examined in the present study. Twelve PCOS patients with hyperandrogenaemia who underwent laparoscopic ovarian wedge resection and 12 age-matched control patients who underwent contralateral ovarian biopsy were enrolled in the study. UCP-2 expression in early stage (primordial, primary and secondary) and late stage (sinus and mature) follicles was examined using immunohistochemistry, whereas UCP-2 and CYP11A1 mRNA and protein levels in ovarian tissue were determined using quantitative reverse transcription–polymerase chain reaction and western blot analyses, respectively. UCP-2 expression increased significantly with follicular development in both control and PCOS tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls. In addition, both UCP-2 and CYP11A1mRNA and protein levels, mean fasting blood glucose concentrations and fasting serum insulin levels were significantly higher in PCOS patients compared with the control group. Finally, a significant correlation between UCP-2 and CYP11A1 expression was found in PCOS but not control patients. In conclusion, in PCOS patients, there was a correlation between UCP-2 and CYP11A1 expression, which was significantly higher than in the control group. These changes in UCP-2 and CYP11A1 expression may mediate follicle development in PCOS.

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Activation profiles of monocyte-macrophages and HDL function in healthy women in relation to menstrual cycle and in polycystic ovary syndrome patients

Endocrine ◽

10.1007/s12020-019-01911-2 ◽

2019 ◽

Vol 66 (2) ◽

pp. 360-369 ◽

Cited By ~ 2

Author(s):

Serena Tedesco ◽

Maria Pia Adorni ◽

Nicoletta Ronda ◽

Roberta Cappellari ◽

Roberto Mioni ◽

...

Keyword(s):

Menstrual Cycle ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Healthy Women ◽

Hdl Function

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Manifestations of Polycystic Ovary Syndrome are Similar Regardless of the Degree of Menstrual Cycle Variation

International Journal of Human and Health Sciences (IJHHS) ◽

10.31344/ijhhs.v6i1.383 ◽

2022 ◽

Vol 6 (1) ◽

pp. 96

Author(s):

Begum Moriom Zamila ◽

Hurjahan Banu ◽

Md Shahed Morshed ◽

Sukanti Shah ◽

Afroza Begum ◽

...

Keyword(s):

Menstrual Cycle ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Cross Sectional Study ◽

Control Group ◽

Menstrual Irregularity ◽

Glycerol Phosphate ◽

Ovary Syndrome ◽

Cross Sectional ◽

Regular Cycle

Background: Menstrual irregularities may predict over adverse consequences in polycystic ovary syndrome (PCOS).Objective: To observe the relation of variants of menstrual cycles with clinical and biochemical features of PCOS.Methods: This cross-sectional study encompassed 200 PCOS women diagnosed by Rotterdam criteria and 120 age-matched healthy controls. Subgroups were classified according to menstrual cycle length as: polymenorrheic (<21 days), eumenorrheic (21-35 days), oligomenorrheic (36 days-3 months) and amenorrheic (>3 months). Glucose was measured by glucose oxidase, lipid by glycerol phosphate dehydrogenenase-peroxidase and all hormones by chemiluminescent immuno-assay method.Results: Around 86% of PCOS patients had menstrual irregularity, among which 75% had oligomenorrhea followed by amenorrhea (9%) and polymenorrhea (2%). All the subgroups of PCOS patients (polymenorrhea excluded from further analyses) had significantly poor metabolic manifestations than the control namely insulin resistance (IR), impaired glycaemic status, general and central obesity, metabolic syndrome and dyslipidaemia. Acanthosis nigricans (AN), hyperandrogenemia (HA) and IR had significant predictive association with PCOS patients with both irregular [OR (95% CI)- AN: 21.994 (6.427, 75.267), p<0.001; HA: 27.735 (8.672, 88.704), p<0.001; IR: 7.268 (2.647, 19.954), p<0.001] and regular cycle [AN: 16.449 (3.830, 70.643), p<0.001; HA: 24.635 (6.349, 95.590), p<0.001; IR: 6.071 (1.658, 22.234), p=0.006] in reference to control group. None of the variables had significant predictive associations with irregular cycle in reference to regular cycle in patients with PCOS.Conclusion: Oligomenorrhea was the most common variant of menstrual irregularity in PCOS patients. All menstrual variants including eumenorrhea had similar manifestations in PCOS women, but poorer than controls.International Journal of Human and Health Sciences Vol. 06 No. 01 January’22 Page: 96-103

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MON-002 The Effect of GNRHR Autoantibody on Reproduction Function and Insulin Signaling Intermediates in a New Animal Model of Polycystic Ovary Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1934 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Hongliang Li ◽

Yankai Guo ◽

Gege Zhang ◽

Jielin Deng ◽

Hayley Fischer ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Inflammatory Cytokines ◽

Insulin Signaling ◽

Solid Phase ◽

Polycystic Ovary ◽

Ovarian Tissue ◽

Peptide Sequence ◽

Control Group ◽

Ovary Syndrome ◽

Reproductive Dysfunction

Abstract Background: Polycystic ovary syndrome (PCOS), a metabolic and reproductive associated disease, defined as hyperandrogenism with reproductive dysfunction including menstrual disorder, anovulation, infertility, polycystic ovary and so on. We previously showed reported a high percentage of activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR) in PCOS patients, and further demonstrated elevated GnRHR-autoantibody (GnRHR-AAb) could induced insulin resistance in energy storage and peripheral tissue in immunized animals. In the present study, we have now induced specific GnRHR-ECL2 AAb in rats and explored the underlying mechanisms of their resultant reproductive dysfunction. Methods: Sixteen SD rats were randomly divided into 2 groups: a GnRHR group (n=8) and a control group (n=8). Rats in the GnRHR group were immunized with GnRHR ECL2 peptide while the controls were not. Epitope mapping of GnRHR-ECL2-directed AAb was performed using octapeptide multipin solid-phase peptides. Rat estrus cycle was measured through pudendum appearance and vaginal smears. Ovarian and pituitary tissues were collected to observe ovarian morphological changes, to examine the expressions of proteins and genes of insulin signaling pathway by Quantitative real-time PCR respectively. The concentration of inflammatory cytokines in the ovary was detected by Bio-plex Pro™ magnetic bead-based assays on the Bio-plex®. Results: The GnRHR-AAb titers and activity in the GnRHR group were significantly higher than the control group, and the GnRHR-AAb from the immunized rats reacted predominantly with the peptide sequence FSQCVTHC of the GnRHR-ECL2. Numbers of LH pulses and concentration of testosterone in GnRHR group were significantly higher than control group. The GnRHR group exhibited lower frequency of in the appearance of proestrus and estrous phases while the control group represented had a higher frequency in the appearance of metestrus and diestrus stages on estrus cyclicity. The GnRHR-immunized group showed demonstrated increased atretic follicles, decreased corpora lutea, loosely packed granulosa cells, and thecal cell hyperplasia in ovarian tissue compared with controls group. There was GnRHR group represented increased expressions of IRS-1, PI3K and GLUT-1 in ovarian and pituitary tissues compared with control group. However, no obvious changes of inflammatory cytokines are observed in ovarian tissues between two groups. Conclusion: Chronic elevated GnRHR-AAb exerts induced reproductive dysfunction through increased ovarian LH secretion and androgen production, thus likely leading to compensatory hyperinsulinemia which ultimately enhanced insulin signaling in reproductive tissues to exert more and androgen production to, which may provide a novel etiological mechanism for PCOS.

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Prognostic value of free testosterone and free androgen index in detecting the polycystic ovary syndrome

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2006-932981 ◽

2006 ◽

Vol 114 (S 1) ◽

Cited By ~ 1

Author(s):

S Hahn ◽

W Kuehnel ◽

S Tan ◽

K Mann ◽

OE Janssen

Keyword(s):

Polycystic Ovary Syndrome ◽

Prognostic Value ◽

Polycystic Ovary ◽

Free Testosterone ◽

Ovary Syndrome ◽

Free Androgen Index

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Urinary bisphenol A in women with polycystic ovary syndrome – a possible suppressive effect on steroidogenesis?

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0032 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Zora Lazúrová ◽

Jana Figurová ◽

Beáta Hubková ◽

Jana Mašlanková ◽

Ivica Lazúrová

Keyword(s):

Polycystic Ovary Syndrome ◽

Bisphenol A ◽

Steroid Hormones ◽

Polycystic Ovary ◽

Suppressive Effect ◽

Human Reproduction ◽

Control Group ◽

Ovary Syndrome ◽

Ovarian Steroidogenesis ◽

The Relationship

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

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