The effect of l-arginine on estrogen level and ovarian cyst in aged rats with polycystic ovaries

Document Type : Research Paper

Authors

1 Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran

2 Department of Pathology, Faculty of Medicine, Shahed University, Tehran, Iran

Abstract

Background and Objective: Menopause in women is associated with many complications that most of them are related to the decrease of estrogen levels in this period. Treatment with high doses of estrogen is common but has side effects. In this study, the effect of l-arginine administration on the level of this hormone in elderly rats was investigated.
Materials and Methods: Elderly Wistar rats were first studied with the help of Papanicolaou test to identify the stage of female sexual cycle. If confirmed to have diestrus phase, the rats were randomly classified into the following groups: control (saline 1 ml/kg, i.p.) and l-arginine group (5, 25, and 50 mg/kg). They were injected saline or l-arginine over a period of three to nine days. At the end, the rats were anesthetized by an i.p. injection of ketamine 100 mg/kg and xylazine 20 mg/kg and the blood samples were collected and the estrogen levels were measured with ELISA kit. The rats’ ovaries and uteri were also biometrically examined and fixed in the formalin. They were stained by H&E method and the number of cysts in the ovaries were counted. Data were analyzed by the ANOVA.
Results: L-arginine at all doses (5-50 mg/kg) during all injection periods from three to nine days significantly increased the estrogen levels, but prominently reduced the ovarian cysts at the lowest dose (5 mg/kg).
Conclusion: Low doses of l-arginine over short periods of time can relieve menopausal problems including estrogen levels and ovarian status, probably by the modulator nitric oxide.

Keywords

References

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2.        Shifren JI, Schiff I. Berek & Novak’s gynecology, 14th ed. Lippincott Williams & Wilkins 2007; 324-338.
3.        Gibbs R, Karlan B, Heny A. Danforth obstetrics and gynecology.10th ed. Lippincott Williams & Wilkins 2008; 725-740.
4.        Rabiee M, Dawati A, Zafarqandi N. Comparison of follicle-stimulating hormone sensitivity and vaginal acidity in the diagnosis of menopause, serum estradiol levels and related symptoms. Journal of Shahid Sadoughi University of Medical Sciences and Health Services, Yazd. 2011; 19(2):72-165.doi:10.5001/omj.2010.4
5.        Kim S-M, Kim S-E, Lee D-Y, Choi D. Serum estradiol level according to dose and formulation of oral estrogens in postmenopausal women. Scientific Reports. 2021;11(1):3585. doi: 10.1038/s41598-021-81201-y.
6.        Burger HG. Physiology and endocrinology of the menopause. Medicine. 2006;1(34):27-30
7.        Burger HG, Dudley EC, Robertson DM, Dennerstein L. Hormonal changes in the menopause transition. Recent Progress in Hormone Research. 2002;57:257-75. doi: 10.1210/rp.57.1.257.
8.        Kazemzadeh R, Nikjou R, Rostamnegad M, Norouzi H. Effect of lavender aromatherapy on menopause hot flushing: a crossover randomized clinical trial. Journal of the Chinese Medical Association. 2016;79(9):489-92. doi: 10.1016/j.jcma.2016.01.020.
9.        Lindsay R. The menopause and osteoporosis. Obstetrics & Gynecology. 1996;87(2 Suppl):16S-19S. doi: 10.1016/0029-7844(95)00430-0.
10.     Sarkar M, Wolf MG. Simple ovarian cysts in postmenopausal women: scope of conservative management. European Journal of Obstetrics & Gynecology and Reproductive Biology 2012;162(1):75-8. doi: 10.1016/j.ejogrb.2011.12.034.
11.     Park J, Kim TH, Lee HH, Lee W, Chung SH. Ovarian rete cyst in a post-menopausal woman: a case report. The Journal of Korean Society of Menopause. 2012;18(1):67-69.https://doi.org/10.6118/jksm.2012.18.1.67
12.     Darblade B, Pendaries C, Krust A, Dupont S, Fouque MJ, Rami J,et al. Estradiol alters nitric oxide production in the mouse aorta through the α-, but not β-, estrogen receptor. Circulation Research. 2002;90(4):413-9. doi: 10.1161/hh0402.105096.
13.     Tsuda K, Kinoshita Y, Nishio I. Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation. American Journal of Hypertension. 2002;15(8):702-8. doi: 10.1016/s0895-7061(02)02965-5.
14.     Tousoulis D, Kampoli AM, Tentolouris Nikolaos Papageorgiou C, Stefanadis C. The role of nitric oxide on endothelial function. Current Vascular Pharmacology. 2012;10(1):4-18. doi: 10.2174/157016112798829760.
15.     Yallampalli C, Byam-Smith M, Nelson SO, Garfield RE. Steroid hormones modulate the production of nitric oxide and cGMP in the rat uterus. Endocrinology. 1994134(4):1971-4 doi: 10.1210/endo.134.4.8137765.
16.     Gol A, Sofiabadi M, Abbasnejad M, Parvizi MR. The Regulatory Effect of Female Sex Steroid Hormones on Nitric Oxid Production. Journal of Rafsanjan University of Medical Sciences 2003;2(3):124-30.
17.     Gol A, Sofiabadi M, Abbasnejad M, Parvizi MR. The Regulatory Effect of Female Sex Steroid Hormones on Nitric Oxid Production. Journal of Rafsanjan University of Medical Sciences 2003;2(3):124-30.
18.     Gore AC, Yeung G, Morrison JH, Oung T. Neuroendocrine aging in the female rat: the changing relationship of hypothalamic gonadotropin-releasing hormone neurons and N-methyl-D-aspartate receptors. Endocrinology 2000;141(12):4757-67. doi: 10.1210/endo.141.12.7841.
19.     Martin CJ, Watson RR, Preedy VR, editors. Nutrition and diet in menopause. Edition: 1stPublisher: Humana PressEditor: Hollins Martin, C.J., Watson, R.R., Preedy, V.R. (Eds.).ISBN: ISBN 978-1-62703-372-5.
20.     Borrow AP, Cameron NM. Estrogenic mediation of serotonergic and neurotrophic systems: implications for female mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;54:13-25. doi: 10.1016/j.pnpbp.2014.05.009.
21.     Horst GJT. Estrogen in the limbic system. Vitamins & Hormones 2010;82:319-38. doi: 10.1016/S0083-6729(10)82017-5.
22.     Veerus P, Hovi SL, Sevón T, Hunter M, Hemminki E. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial. BMC Research Notes 2012;5:176. doi: 10.1186/1756-0500-5-176.
23.     Khan A, Fortier M. Menopause and osteoporosis. Journal of Obstetrics and Gynaecology Canada 2014; 36(9):839-840. doi: 10.1016/S1701-2163(15)30489-8.
24.     Menati L, Khaleghinezhad K, Tadayon M, Siahpoosh A. Evaluation of contextual and demographic factors on licorice effects on reducing hot flashes in postmenopause women. Health Care for Women International 2014;35(1):87-99. doi: 10.1080/07399332.2013.770001.
25.     Panay N, Hamoda H, Arya R, Savvas M. The 2013 British menopause society & women’s health concern recommendations on hormone replacement therapy. Menopause International 2013;19(2):59-68. doi: 10.1177/1754045313489645.
26.     Salvemini D, Ischiropoulos H, Cuzzocrea S. Roles of nitric oxide and superoxide in inflammation. Methods in molecular biology 2003:225:291-303. doi: 10.1385/1-59259-374-7:291.
27.     Cella M, Farina MG, Dominguez Rubio AP, Di Girolamo G, Ribeiro ML, Franchi AM. Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour. British Journal of Pharmacology 2010;161(4):844-55. doi: 10.1111/j.1476-5381.2010.00911.x.
28.     Tamanini C, Basini G, Grasselli F, Tirelli M. Nitric oxide and the ovary. Journal of Animal Science 2003;81(14_suppl_2):E1-7.
29.     Van Voorhis BJ, Dunn MS, Snyder GD, Weiner CP. Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis. Endocrinology 1994;135(5):1799-806. doi: 10.1210/endo.135.5.7525252.
30.     Olson LM, Jones-Burton CM, Jablonka-Shariff AL. Nitric oxide decreases estradiol synthesis of rat luteinized ovarian cells: possible role for nitric oxide in functional luteal regression. Endocrinology 1996;137(8):3531-9. doi: 10.1210/endo.137.8.8754783.
31.     Fatemeh Lakzaei, Manizheh Karami, Mohammadreza Jalali Nadoushan, Fatemeh Hassani. Opposite effect of naloxone on infertility induced by nitric oxide system in an animal model of polycystic ovary. Daneshvar Medicine 2014; 21(110):85-94.
1.        Speroff L, Fritz M. Clinical Gynecology endocrinology and infertility. 2nd ed. Williams & Wilkins 2005; 21-24.
2.        Shifren JI, Schiff I. Berek & Novak’s gynecology, 14th ed. Lippincott Williams & Wilkins 2007; 324-338.
3.        Gibbs R, Karlan B, Heny A. Danforth obstetrics and gynecology.10th ed. Lippincott Williams & Wilkins 2008; 725-740.
4.        Rabiee M, Dawati A, Zafarqandi N. Comparison of follicle-stimulating hormone sensitivity and vaginal acidity in the diagnosis of menopause, serum estradiol levels and related symptoms. Journal of Shahid Sadoughi University of Medical Sciences and Health Services, Yazd. 2011; 19(2):72-165.doi:10.5001/omj.2010.4
5.       
45
Kim S-M, Kim S-E, Lee D-Y, Choi D. Serum estradiol level according to dose and formulation of oral estrogens in postmenopausal women. Scientific Reports. 2021;11(1):3585. doi: 10.1038/s41598-021-81201-y.
6.        Burger HG. Physiology and endocrinology of the menopause. Medicine. 2006;1(34):27-30
7.        Burger HG, Dudley EC, Robertson DM, Dennerstein L. Hormonal changes in the menopause transition. Recent Progress in Hormone Research. 2002;57:257-75. doi: 10.1210/rp.57.1.257.
8.        Kazemzadeh R, Nikjou R, Rostamnegad M, Norouzi H. Effect of lavender aromatherapy on menopause hot flushing: a crossover randomized clinical trial. Journal of the Chinese Medical Association. 2016;79(9):489-92. doi: 10.1016/j.jcma.2016.01.020.
 
9.        Lindsay R. The menopause and osteoporosis. Obstetrics & Gynecology. 1996;87(2 Suppl):16S-19S. doi: 10.1016/0029-7844(95)00430-0.
10.     Sarkar M, Wolf MG. Simple ovarian cysts in postmenopausal women: scope of conservative management. European Journal of Obstetrics & Gynecology and Reproductive Biology 2012;162(1):75-8. doi: 10.1016/j.ejogrb.2011.12.034.
11.     Park J, Kim TH, Lee HH, Lee W, Chung SH. Ovarian rete cyst in a post-menopausal woman: a case report. The Journal of Korean Society of Menopause. 2012;18(1):67-69.https://doi.org/10.6118/jksm.2012.18.1.67
12.     Darblade B, Pendaries C, Krust A, Dupont S, Fouque MJ, Rami J,et al. Estradiol alters nitric oxide production in the mouse aorta through the α-, but not β-, estrogen receptor. Circulation Research. 2002;90(4):413-9. doi: 10.1161/hh0402.105096.
13.     Tsuda K, Kinoshita Y, Nishio I. Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation. American Journal of Hypertension. 2002;15(8):702-8. doi: 10.1016/s0895-7061(02)02965-5.
14.     Tousoulis D, Kampoli AM, Tentolouris Nikolaos Papageorgiou C, Stefanadis C. The role of nitric oxide on endothelial function. Current Vascular Pharmacology. 2012;10(1):4-18. doi: 10.2174/157016112798829760.
15.     Yallampalli C, Byam-Smith M, Nelson SO, Garfield RE. Steroid hormones modulate the production of nitric oxide and cGMP in the rat uterus. Endocrinology. 1994134(4):1971-4 doi: 10.1210/endo.134.4.8137765.
16.     Gol A, Sofiabadi M, Abbasnejad M, Parvizi MR. The Regulatory Effect of Female Sex Steroid Hormones on Nitric Oxid Production. Journal of Rafsanjan University of Medical Sciences 2003;2(3):124-30.
17.     Gol A, Sofiabadi M, Abbasnejad M, Parvizi MR. The Regulatory Effect of Female Sex Steroid Hormones on Nitric Oxid Production. Journal of Rafsanjan University of Medical Sciences 2003;2(3):124-30.
18.     Gore AC, Yeung G, Morrison JH, Oung T. Neuroendocrine aging in the female rat: the changing relationship of hypothalamic gonadotropin-releasing hormone neurons and N-methyl-D-aspartate receptors. Endocrinology 2000;141(12):4757-67. doi: 10.1210/endo.141.12.7841.
19.     Martin CJ, Watson RR, Preedy VR, editors. Nutrition and diet in menopause. Edition: 1stPublisher: Humana PressEditor: Hollins Martin, C.J., Watson, R.R., Preedy, V.R. (Eds.).ISBN: ISBN 978-1-62703-372-5.
20.     Borrow AP, Cameron NM. Estrogenic mediation of serotonergic and neurotrophic systems: implications for female mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;54:13-25. doi: 10.1016/j.pnpbp.2014.05.009.
21.     Horst GJT. Estrogen in the limbic system. Vitamins & Hormones 2010;82:319-38. doi: 10.1016/S0083-6729(10)82017-5.
22.    
46
Veerus P, Hovi SL, Sevón T, Hunter M, Hemminki E. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial. BMC Research Notes 2012;5:176. doi: 10.1186/1756-0500-5-176.
23.     Khan A, Fortier M. Menopause and osteoporosis. Journal of Obstetrics and Gynaecology Canada 2014; 36(9):839-840. doi: 10.1016/S1701-2163(15)30489-8.
24.     Menati L, Khaleghinezhad K, Tadayon M, Siahpoosh A. Evaluation of contextual and demographic factors on licorice effects on reducing hot flashes in postmenopause women. Health Care for Women International 2014;35(1):87-99. doi: 10.1080/07399332.2013.770001.
25.     Panay N, Hamoda H, Arya R, Savvas M. The 2013 British menopause society & women’s health concern recommendations on hormone replacement therapy. Menopause International 2013;19(2):59-68. doi: 10.1177/1754045313489645.
26.     Salvemini D, Ischiropoulos H, Cuzzocrea S. Roles of nitric oxide and superoxide in inflammation. Methods in molecular biology 2003:225:291-303. doi: 10.1385/1-59259-374-7:291.
27.     Cella M, Farina MG, Dominguez Rubio AP, Di Girolamo G, Ribeiro ML, Franchi AM. Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour. British Journal of Pharmacology 2010;161(4):844-55. doi: 10.1111/j.1476-5381.2010.00911.x.
28.     Tamanini C, Basini G, Grasselli F, Tirelli M. Nitric oxide and the ovary. Journal of Animal Science 2003;81(14_suppl_2):E1-7.
 
29.     Van Voorhis BJ, Dunn MS, Snyder GD, Weiner CP. Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis. Endocrinology 1994;135(5):1799-806. doi: 10.1210/endo.135.5.7525252.
30.     Olson LM, Jones-Burton CM, Jablonka-Shariff AL. Nitric oxide decreases estradiol synthesis of rat luteinized ovarian cells: possible role for nitric oxide in functional luteal regression. Endocrinology 1996;137(8):3531-9. doi: 10.1210/endo.137.8.8754783.
31.     Fatemeh Lakzaei, Manizheh Karami, Mohammadreza Jalali Nadoushan, Fatemeh Hassani. Opposite effect of naloxone on infertility induced by nitric oxide system in an animal model of
 
Journal of Basic and Clinical Pathophysiology
Volume 9, Issue 1
May 2021
Pages 41-46

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