Kisspeptin, GnRH, Prolactin and Ovarian Hormones Levels in Hyperprolactinemia, Type 1 Diabetes and Obesity Women
الموضوعات :
Nakaa Qassim Ghali
1
,
Zainab Abduljabbar Ridha Al-Ali
2
,
Saba Jassim Al Heshimi
3
1 - Department of Biology, College of Science, University of Misan, Maysan, Iraq
2 - Department of Biology, College of Science, University of Misan, Maysan, Iraq
3 - College of Medicine, University of Misan, Maysan, Iraq
الکلمات المفتاحية: Women, Hyperprolactinemia, Kisspeptin, Obesity, GnRH,
ملخص المقالة :
Kisspeptin is a peptide that plays a crucial function in the regulation of puberty initiation, by sexual immaturity and slowed puberty advancement. Infertility is a result of hyperprolactinemia, which inhibits the pulsatile release of GnRH from the brain and lowers the pulsatile production of LH from the pituitary. In type 1 diabetes, also known as autoimmune diabetes, pancreatic cells die off and the body cannot produce enough insulin, leading to high blood sugar levels. Obese people are more likely to suffer from hyperinsulinemia, hyperlipidemia, hyperleptinemia, chronic inflammation, menstrual abnormalities, pregnancy troubles, and infertility. So, this study aims to know the reproductive status of women by estimating kisspeptin and other hormones. The study was conducted on 92 women, ages (20-40) years, Samples were collected from the AL-Sader Teaching Hospital, Maysan for Child and Birth Hospital, the specialized Centre for Diabetes and Endocrinology and some private clinics and centres, the period June 2022 to February of 2023. The women were divided equally into four groups: control group (with regular menstrual cycles), hyperprolactinemia group (hyper serum prolactin), obesity group (have a BMI over 30 kg.m–2), and type 1 diabetes group. The results showed the values of kisspeptin did not differ significantly (P>0.05) in all groups, values of GnRH in hyperprolactinemia, obesity and type 1 DM groups increased significantly (P≤0.05) compared with the control group, Prolactin, estradiol and progesterone in the hyperprolactinemia group increased significantly (P≤0.05) in comparison with other groups. According to the above results, we conclude that high levels of prolactin, also obesity and type 1 DM influence the reproductive hormones in women.
1. Kotani M., Detheux M., Vandenbogaerde A., Communi D., Vanderwinden J.M., Le Poul E., Brézillon S., Tyldesley R., Suarez-Huerta N., Vandeput F., Blanpain C., 2001. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry. 276(37), 34631-34636.
2. Tena-SempereM., 2006. GPR54 and kisspeptin in reproduction. Human Reproduction Update. 12(5), 631-639.
3. De Roux N., Genin E., Carel J.C., Matsuda F., Chaussain J.L., Milgrom E., 2003. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proceedings of the National Academy of Sciences. 100(19), 10972-10976.
4. Seminara S.B., Messager S., Chatzidaki E.E., Thresher R.R., Acierno Jr J.S., Shagoury J.K., Bo-Abbas Y., Kuohung W., Schwinof K.M., Hendrick A.G., Zahn D.,2003.The GPR54 gene as a regulator of puberty. New England Journal of Medicine. 349(17), 1614-1627.
5. Dungan H.M., Gottsch M.L., Zeng H., Gragerov A., Bergmann J.E., Vassilatis D.K., Clifton D.K., Steiner R.A., 2007. The role of kisspeptin–GPR54 signaling in the tonic regulation and surge release of gonadotropin-releasing hormone/luteinizing hormone. Journal of Neuroscience. 27(44), 12088-12095.
6. Pineda R., Garcia-Galiano D., Roseweir A., Romero M., Sanchez-Garrido M.A., Ruiz-Pino F., Morgan K., Pinilla L., Millar R.P., Tena-Sempere M., 2010. Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist. Endocrinology. 151(2), 722-730.
7. Brown R.S., Khant Aung Z., Phillipps H.R., Barad Z., Lein H.J., Boehm U., Szawka R.E., Grattan D.R., 2019. Acute suppression of LH secretion by prolactin in female mice is mediated by kisspeptin neurons in the arcuate nucleus. Endocrinology. 160(5), 1323-1332.
8. Araujo-Lopes R., Crampton J.R., Aquino N.S., Miranda R.M., Kokay I.C., Reis A.M., Franci C.R., Grattan D.R., Szawka R.E.,2014.Prolactin regulates kisspeptin neurons in the arcuate nucleus to suppress LH secretion in female rats. Endocrinology. 155(3), 1010-1020.
9. Capozzi A., Scambia G., Pontecorvi A., Lello S.,2015.Hyperprolactinemia: pathophysiology and therapeutic approach. Gynecological Endocrinology. 31(7), 506-510.
10. Kokay I.C., Petersen S.L., Grattan D.R., 2011. Identification of prolactin-sensitive GABA and kisspeptin neurons in regions of the rat hypothalamus involved in the control of fertility. Endocrinology. 152(2), 526-535.
11. Katsarou A., Gudbjörnsdottir S., Rawshani A., Dabelea D., Bonifacio E., Anderson B.J., Jacobsen L.M., Schatz D.A. ,Lernmark Å., 2017. Type 1 diabetes mellitus. Nature Reviews Disease Primers. 3(1), 1-17.
12. Codner E., Merino P.M., Tena-Sempere M., 2012. Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Human Reproduction Update. 18(5), 568-585.
13. Kjaer K., Hagen C., Sandø S.H., Eshøj O., 1992. Epidemiology of menarche and menstrual disturbances in an unselected group of women with insulin-dependent diabetes mellitus compared to controls. The Journal of Clinical Endocrinology & Metabolism. 75(2), 524-529.
14. Strotmeyer E.S., Steenkiste A.R., Foley Jr T.P., Berga S.L., Dorman J.S., 2003. Menstrual cycle differences between women with type 1 diabetes and women without diabetes. Diabetes Care. 26(4), 1016-1021.
15. Codner E., Soto N., Merino P.M., 2012. Contraception and pregnancy in adolescents with type 1 diabetes: a review. Pediatric Diabetes. 13(1), 108-123.
16. Deltsidou A., 2010. Age at menarche and menstrual irregularities of adolescents with type 1 diabetes. Journal of Pediatric and Adolescent Gynecology. 23(3), 162-167.
17. Gaete X., Vivanco M., Eyzaguirre F.C., López P., Rhumie H.K., Unanue N., Codner E., 2010. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertility and Sterility. 94(5), 1822-1826.
18. Picardi A., Cipponeri E., Bizzarri C., Fallucca S., Guglielmi C. , Pozzilli P., 2008. Menarche in type 1 diabetes is still delayed despite good metabolic control. Fertility and Sterility. 90(5), 1875-1877.
19. Yeshaya A., Orvieto R., Dicker D., Karp M., Ben-Rafael Z., 1995. Menstrual characteristics of women suffering from insulin-dependent diabetes mellitus. International Journal of Fertility and Menopausal Studies. 40(5), 269-273.
20. Adcock C.J., Perry L.A., Lindsell D.R.M., Taylor A.M., Holly J.M.P., Jones J., Dunger D.B., 1994. Menstrual irregularities are more common in adolescents with type 1 diabetes: association with poor glycaemic control and weight gain. Diabetic Medicine. 11(5), 465-470.
21. Zachurzok A., Deja G., Gawlik A., Drosdzol-Cop A., Małecka-Tendera E., 2013. Hyperandrogenism in adolescent girls with type 1 diabetes mellitus treated with intensive and continuous subcutaneous insulin therapy. Endokrynologia Polska. 64(2), 121-128.
22. Samara-Boustani D., Colmenares A., Elie C., Dabbas M., Beltrand J., Caron V., Ricour C., Jacquin P., Tubiana-Rufi N., Levy-Marchal C., Delcroix C., 2012. High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles. European Journal of Endocrinology. 166(2), 307-316.
23. Whitworth K.W., Baird D.D., Stene L.C., Skjaerven R., Longnecker M.P., 2011. Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study. Diabetologia. 54, 516-522.
24. Dorman J.S., Steenkiste A.R., Foley T.P., Strotmeyer E.S., Burke J.P., Kuller L.H., Kwoh C.K., 2001. Menopause in type 1 diabetic women: is it premature? Diabetes. 50(8), 1857-1862.
25. Wild D., 2013. The immunoassay handbook: theory and applications of ligand binding, ELISA and related techniques. 4 th ed., Elsevier. Oxford.
26. Risvanli A., Ocal H., Timurkaan N., Ipek P., Seker I., Karabulut B., 2020. Expression of the anti-Mullerian hormone, kisspeptin 1, and kisspeptin 1 receptor in polycystic ovary syndrome and controlled ovarian stimulation rat models. Bosnian Journal of Basic Medical Sciences. 20(1), 37.
27.Fung A.W., Knauer M.J., Blasutig I.M., Colantonio, D.A., Kulasingam, V.,2017.Evaluation of electrochemiluminescence immunoassays for immunosuppressive drugs on the Roche cobas e411 analyzer. F1000Research. 6, 1832
28. Arslan İ.E., Öztürk B.O., Bolayır B., Yalçın M.M., Yetkin İ., Aktürk M., 2022. Circulating Kisspeptin and Klotho Levels in Women with Hyperprolactinemia. Turkish Journal of Endocrinology & Metabolism. 26(3), 115-119.
29. Hoskova K., Kayton Bryant N., Chen M.E., Nachtigall L.B., Lippincott M.F., Balasubramanian R. , Seminara S.B., 2022. Kisspeptin overcomes GnRH neuronal suppression secondary to hyperprolactinemia in humans. The Journal of Clinical Endocrinology & Metabolism. 107(8), e3515-e3525.
30. Mancini A., Curro D., Cipolla C., Barini A., Bruno C., Vergani E., Di Segni C., Guidi F., Nicolotti N., Silvestrini A., Meucci E., 2021. Evaluation of Kisspeptin levels in prepubertal obese and overweight children: sexual dimorphism and modulation of antioxidant levels. European Review for Medical & Pharmacological Sciences. 25(2), 941-949.
31. Rafique N., Latif R., 2015. Serum kisspeptin levels in normal and overweight Saudi females and its relation with anthropometric indices. Annals of Saudi Medicine. 35(2), 157-160.
32. Arikan F.B., Sagsoz N., 2023. Effects of obesity on the serum bmp15, GDF9, and kisspeptin concentrations in women of reproductive age. Journal of Medical Biochemistry. 42(3), 392-400.
33. Pruszyńska-Oszmałek E., Wojciechowska M., Krauss H., Sassek M., Leciejewska N., Szczepankiewicz D., Nowak K.W., Piątek J., Nogowski L., Sliwowska J.H. , Kołodziejski P.A., 2021. Obesity is associated with increased level of kisspeptin in mothers' blood and umbilical cord blood-a pilot study. European Review for Medical & Pharmacological Sciences. 25(19) 5993-6002.
34. Kołodziejski P.A., Pruszyńska-Oszmałek E., Korek E., Sassek M., Szczepankiewicz D., Kaczmarek P., Nogowski L., Maćkowiak P., Nowak K.W., Krauss H. , Strowski M.Z., 2018. Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women. Physiological Research. 67(1), 45-56.
35. Shi L., Jiang Z., Zhang L., 2022. Childhood obesity and central precocious puberty. Frontiers in Endocrinology. 13, 3004.
36. Pan H., Li N., Wu Q., 2016. The changes of serum leptin and kisspeptin levels in Chinese children and adolescents in different pubertal stages. International Journal of Endocrinology. 2016(1), 1-11.
37. Izzi-Engbeaya C., Patel B., Mills E., Phylactou M., Clarke S., Comninos A., Abbara A., Tan T. , Dhillo W., 2023. The effects of kisspeptin on food intake in women with overweight or obesity. Diabetes Obes Metab. 25(8), 2393-2397.
38. Calcaterra V., Nappi R.E., Pelizzo G., De Silvestri A., Albertini R., De Amici M., Tenuta E., Vinci F., Mameli C., Zuccotti G., 2021. Insulin resistance and potential modulators of ovarian reserve in young reproductive-aged women with obesity and type 1 diabetes. Gynecological Endocrinology. 37(9), 823-830.
39. Hussain M.A., Song W.J., Wolfe A., 2015. There is kisspeptin–and then there is kisspeptin. Trends in Endocrinology & Metabolism. 26(10), 564-572.
40. Abbara A., Al-Memar M., Phylactou M., Daniels E., Patel B., Eng P.C., Nadir R., Izzi-Engbeaya C., Clarke S.A., Mills E.G., Hunjan T., 2022.Changes in circulating kisspeptin levels during each trimester in women with antenatal complications. The Journal of Clinical Endocrinology & Metabolism. 107(1), e71-e83.
41. Nappi R.E., Di Ciaccio S., Genazzani A.D., 2021. Prolactin as a neuroendocrine clue in sexual function of women across the reproductive life cycle: an expert point of view. Gynecological Endocrinology. 37(6), 490-496.
42. Triantafyllou G.A., Paschou S.A., Mantzoros C.S., 2016. Leptin and hormones: energy homeostasis. Endocrinology and Metabolism Clinics. 45(3), 633-645.
43. Toor S., Yardley J.E., Momeni Z., 2023. Type 1 Diabetes and the Menstrual Cycle: Where/How Does Exercise Fit in? International Journal of Environmental Research and Public Health. 20(4), 2772.
44. Elnour A.A.A., Javed M., Elkhier M.K.S., 2021. Comparison of prolactin, follicle-stimulating hormone, luteinizing hormone, estradiol, thyroid-stimulating hormone, free thyroxine and body mass index between infertile and fertile Saudi women. Obstetrics & Gynecology International Journal. 12(2), 119-122.
45. Owiredu W.K., Ofori P.N., Turpin C.A., Obirikorang C., Acheampong E., Anto E.O., Owiredu E.W. , Adu E.A., 2019. Weight management merits attention in women with infertility: a cross-sectional study on the association of anthropometric indices with hormonal imbalance in a Ghanaian population. BMC Research Notes. 12, 1-7.
46. Posawetz A.S., Trummer C., Pandis M., Aberer F., Pieber T.R., Obermayer-Pietsch B., Pilz S. , Theiler-Schwetz V., 2021. Adverse body composition and lipid parameters in patients with prolactinoma: a case-control study. BMC Endocrine Disorders. 21(1), 1-9.
47. Al-Ttaie F.K., Aljawadi Z.A., 2021. Hormonal and biochemical study of the effect of obesity on women infertility. Journal of Health and Translational Medicine (JUMMEC). 24(1), 53-57.
48. Giviziez C.R., Sanchez E.G.D.M., Lima Y.A.R.D., Approbato M.S., 2022. Association of overweight and consistent anovulation among infertile women with regular menstrual cycle: a case-control study. Revista Brasileira de Ginecologia e Obstetrícia. 43, 834-839.
49. Ahmed F., Kamble P.G., Hetty S., Fanni G., Vranic M., Sarsenbayeva A., Kristófi R., Almby K., Svensson M.K., Pereira M.J., Eriksson J.W., 2022. Role of estrogen and its receptors in adipose tissue glucose metabolism in pre-and postmenopausal women. The Journal of Clinical Endocrinology & Metabolism. 107(5), e1879-e1889.
50. Rehman R., Hussain Z., Faraz N., 2012. Effect of estradiol levels on pregnancy outcome in obese women. Journal of Ayub Medical College Abbottabad. 24(3-4), 3-5.
51. Stárka L., Martin H.I.L.L., Pospíšilová H., Dušková M., 2020. Estradiol, obesity and hypogonadism. Physiological Research. 69(Suppl 2), S273.
52. Salman S.A., Yser H.T., 2022. Evaluation of some physiological parameters for obese women suffering from pregnant disturbance in Basrah Governorate, Iraq-Case Study. Revista Latinoamericana de Hipertension. 17(1), 53-62.
53. Yi Y., El Khoudary S.R., Buchanich J.M., Miller R.G., Rubinstein D., Matthews K., Orchard T.J. ,d Costacou T., 2021. Women with Type 1 diabetes (T1D) experience a shorter reproductive period compared with nondiabetic women: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study and the Study of Women's Health Across the Nation (SWAN). Menopause (New York, NY). 28(6), 634.
54. Gaete X., Vivanco M., Eyzaguirre F.C., López P., Rhumie H.K., Unanue N., Codner E., 2010. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertility and Sterility. 94(5), 1822-1826.
