A remarkable Activity of Steroid Biosynthesis in Captopril Preserved Leydig Cells of Mice Implicated Leukotriene B4 and Gonadotropin Releasing Hormones in vitro
American Journal of BioScience
Volume 2, Issue 6, November 2014, Pages: 203-210
Received: Oct. 30, 2014; Accepted: Nov. 12, 2014; Published: Nov. 17, 2014
Views 3159      Downloads 148
Mohanad A. Al-Bayati, Pharmacology and Toxicology, Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq
Article Tools
Follow on us
In this study, investigated whether captopril inhibited steroidogenesis and components of the Leukotriene B4 pathways are involved in GnRH agonist (GnRH)-induced testis steroidogenesis in mice Leydig cells. Primary cultures of mice Leydig cells were established. Purified Leydig cells from adult albino mice were incubated with gradual various concentrations of GnRH with and without Captopril, Luteinizing hormone (LH); LTB4, steroidogenic (testosterone) activity and LTB4 concentration were measured after various time intervals and Leydig cell viability. The maneuvers of Leydig cells treated media was covered the singular and dual actions of antisteroidogenic of captopril and the reversible activity by GnRH-LTB4 as well as contribution of LTB4 in Leydig cells testosterone production endpoint. The different treatment media are Medium alone; Medium plus captopril 60 μM, 65 μM, 70 μM, 75 μM and 80 μM 100 μM; Medium plus 2.5mU/ml leukotriene B4; Medium plus 0.1 mM LH; Medium plus 0.1 μM GnRH; Medium plus 65 μM captopril plus 2.5 mU/ml leukotriene B4;Medium plus 65 μM captopril plus 0.1 mM LH; Medium plus 65 μM captopril plus 0.1 mM GnRH; Medium plus 0.1 mM GnRH plus 2.5 mU/ml leukotriene B4 and Medium plus 65 μM captopril plus 0.1 mM GnRH plus 2.5 mU/ml leukotriene B4. Basal testosterone levels were maximal at 0.1 μM GnRH concentration and superior testosterone yield in Leydig cells incubated 0.1 μM GnRH media than without GnRH media, and the activity profile LTB4 flow up. That comparable result led to highly correlated approved the contribution of LTB4 in GnRH stimulated Leydig cell steroidogenic end point. Furthermore captopril had an abolishment effect partially of testosterone yield and recovered and improved by GnRH and LTB4. The Leydig cells viability results suggest that the major effect of GnRH is probably beyond the LTB4. The entire key; GnRH induced testosterone production and upregulated LTB4 Levels at both the captopril inhibitory LTB4-testesteron Leydig cells culture media and captopril abolished LTB4 levels; it also activated endogenous LTB4, but not LH motivated testosterone pathway. Our data show that GnRH positively regulates steroidogenesis via LTB4 signaling in mice Leydig cells. LTB4 activation by GnRH may be responsible for the induction of Ca++ signaling indirect. Possibility improve the captopril steroidogenic disruption in Leydig cells via LTB4 and/or GnRH induction of endogenous LTB4, likewise the positive maintenance of Leydig cells viability matched induce testosterone synthesis. The LTB4 production, which may ultimately modulate steroidogenesis in mice Leydig cells, and promise new antidotal and preventative of captopril adverse effects.
Captopril, Leukotriene B4, GnRH, Testosterone, Leydig Cell, LTB4, Steroidogenic
To cite this article
Mohanad A. Al-Bayati, A remarkable Activity of Steroid Biosynthesis in Captopril Preserved Leydig Cells of Mice Implicated Leukotriene B4 and Gonadotropin Releasing Hormones in vitro, American Journal of BioScience. Vol. 2, No. 6, 2014, pp. 203-210. doi: 10.11648/j.ajbio.20140206.13
Zhang L. and Cui S., “Effects of daidzein on testosterone synthesis and secretion in cultured mouse leydig cells,” Asian-Australasian Journal of Animal Sciences, vol. 22, no. 5, pp. 618–625, 2009.
Shuying Huo, Xiuhui Zhong, Xianjun Wu, and Yurong Li, “Effects of Norepinephrine and Acetylcholine on the Development of Cultured Leydig Cells in Mice,” Journal of Biomedicine and Biotechnology, vol. 2012, Article ID 503093, 8 pages, 2012. doi:10.1155/2012/503093
Zhao, M., J. Rohozinski, M. Sharma, J. Ju, R.E. Braun, C.E. Bishop, and M.L. Meistrich. 2007. Utp14b: a unique retrogene within a gene that has acquired multiple promoters and a specific function in spermatogenesis. Dev. Biol. 304:848-859.
Anway, M.D., J. Folmer, W.W. Wright, and B.R. Zirkin. 2003. Isolation of sertoli cells from adult rat testes: an approach to ex vivo studies of Sertoli cell function. Biol. Reprod. 68:996-1002.
O’Shaughnessy, P.J., I.D. Morris, I. Huhtaniemi, P.J. Baker, and M.H. Abel. 2009. Role of androgen and gonadotrophins in the development and function of the Sertoli cells and Leydig cells: data from mutant and genetically modified mice. Mol. Cell. Endocrinol. 306:2-8.
Cheng, C.Y. and D.D. Mruk. 2010. A local autocrine axis in the testes that regulates spermatogenesis. Nat. Rev. Endocrinol. 6:380-395.
Luteinizing Hormone Receptors and Testosterone Synthesis in Two Distinct Populations of Ley dig Cells ANITA H. PAYNE, JAMES R. DOWNING, and KAR-LIT WONG Endocrinology 1980 106:5, 1424-1429
Guoxin Wang, Dawei Chen, Haoshu Luo, Jiali Liu, Xiaowen Ji, Jingjing Fan, Sheng Cui 2010., “Low-dose ethanol suppresses17β-estradiol activity in GH4C1 pituitary tumor cells,” Cell Biology and Toxicology, Vol. 26, no. 3, pp. 265-277, 2010.
Huamin J, Ci Z, Hui S, Yong L, Huijun Q, Bingyan Z (2002). Determination of pretransplant viability of Leydig cells by MTT colorimetric assay. Transplant Proc. 34(8):3419-21
Wang N. G, Sundaram K, Pavlou S, Rivier J, Vale W, Bardin CW. (1983) Mice are insensitive to the antitesticular effects of luteinizing hormone-releasing hormone agonists. Endocrinology; 112: 331–5.
K Shindo, J R Baker, D A Munafo, and T D Bigby (1994) Captopril inhibits neutrophil synthesis of leukotriene B4 in vitro and in vivo. J Immunol ; 153:5750-9
Chen Barbara B, Helen Chen, Malecha James W, Miyashiro Julie M, Penning Thomas D, Russell Mark A. (1998) LTB4 hydrolase inhibitors; invention WO 1998040364 A1
Ludwig K., Andrzej F., Andreas J., Maria S. Przylipiak, and Benno R. (1991) Production of leukotrienes in gonadotropin-releasing hormone-stimulated pituitary cells: Potential role in luteinizing hormone release Proc. Nati. Acad. Sci. USA Vol. 88, pp. 8801-8805,
Lin, Yung-Ming Lin, Ming-Yie Liu, Song-Ling Poon, Sew-Fen Leu, Bu-Miin Huang (2008) Gonadotrophin-releasing hormone-I and -II stimulate steroidogenesis in prepubertal murine Leydig cells in vitro. Asian J Androl; 10 (6): 929–936
Sullivan, M. and Brian A. (1985) Control and production of leukotriene B4 in rat tumour and testicular Leydig cells Biochem. J. 230, 821-824
PJ Baker, H Johnston, M Abel, HM Charlton and PJ O'Shaughnessy (2003) Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice Reproductive Biology and Endocrinology, 1:4
Shapiro, R. and Riordan, J.F. (1984) Biochemistry. 23: 5225-5233.
Antonino M., Anna G., Massimo Z., Luna Q., Ennio M., Oretta M., Domenico A., and Massimo B. (1999) the American Physiological Society R1261-R1267
Tu Un (1984) Mechanism of Action of Gonadotropin-releasing Hormone-stimulated Leydig Cell Steroidogenesis, I. The Stimulatory Effect is Calcium Dependent and Not Mediated by Cyclic Nucleotides J. Androl., 5:193-200.
Bing Yao, Hai-Yan Liu, Yu-Chun Gu, Shan-Shan Shi, Xiao-Qian Tao, Xiao-Jun Li, Yi-Feng Ge, Ying-Xia Cui and Guo-Bin Yang (2011) Gonadotropin-releasing hormone positively regulates steroidogenesis via extracellular signal-regulated kinase in rat Leydig cells. Asian Journal of Andrology, 13, 438–445
Tobin V. A. and Canny B. J. (1998) The Regulation of Gonadotropin-Releasing Hormone- Induced Calcium Signals in Male Rat Gonadotrophs by Testosterone Is Mediated by Dihydrotestosterone. Endocrinology Vol. 139, No. 3 1038-1045
WANG Ju—Feng, XIAO W en—Bin (1993) Effects of lisinopril and captopril on calcium in rat heart. Acta Pharma~ologica Sinica ; 14(3):197—200
Soichi Yamashita, Ping Tai, Jean Charron, CheMyong Ko, and Mario Ascoli (2011) The Leydig Cell MEK/ERK Pathway Is Critical for Maintaining a Functional Population of Adult Leydig Cells and for Fertility, Mol Endocrinol. Jul 2011; 25(7): 1211–1222
Nan Hu, Yu Li, Yu Zhao, Qi Wang, Jia-cong You, Xiao-dong Zhang and Li-hong Ye (2011) A novel positive feedback loop involving FASN/p-ERK1/2/5-LOX/LTB4/FASN sustains high growth of breast cancer cells, Acta Pharmacologica Sinica (2011) 32: 921–929; 40.
Shindo K, Baker JR, Munafo DA, Bigby TD. (1994) Captopril inhibits neutrophil synthesis of leukotriene B4 in vitro and in vivo. J. Immunol. 15; 153(12):5750-9.
Schilsky R. L., Lewis B. J., Sherins R. J., and Young R. C., “Gonadal dysfunction in patients receiving chemotherapy for cancer,” Annals of Internal Medicine, vol. 93, no. 1, pp. 109–114, 1980.
Molcho J, Zakut H, Naor Z. (1984) Stimulation of prostaglandin E and testosterone production in rat interstitial cells by a gonadotropin-releasing hormone agonist. Endocrinology; 114: 2382–7.
Browning JY, D’Agata R, Steinberger A, Grotjan Jr. HE, Steinberger E. (1983) Biphasic effect of gonadotropin-releasing hormone and its agonist analog (HOE766) on in vitro testosterone production by purified rat Leydig cells. Endocrinology; 113: 985–91.
Kerr JB, Sharpe RW. (1986) Effects and interactions of LH and LHRH agonists on testicular morphology and function in hypophysectomized rats; J Reprod Fertil; 76: 175–92.
Habert R. (1992) Effect of decapitation and chronic in-vivo treatment with a gonadotrophin-releasing hormone agonist on testicular steroidogenesis in the rat fetus. J Endocrinol, 133: 245– 51.
Romanelli F, Valenca M, Conte D, Isidori A, and Negro-Vilar A. (1995) Arachidonic acid and its metabolites effects on testosterone production by rat Leydig cells. J Endocrinol. Invest; 18(3):186-93.
Mi Kyung Park, Youngran Park, Jaegal Shim, Hye Ja Lee, Sanghee Kim, Chang Hoon Lee (2012) Novel involvement of leukotriene B4 receptor 2 through ERK activation by PP2A down-regulation in leukotriene B4-induced keratin phosphorylation and reorganization of pancreatic cancer cells Biochimica et Biophysica Acta 1823 (2012) 2120–2129.
Meztli Arguello, Suzanne Paz, Eduardo Hernandez, Catherine Corriveau-Bourque, Lama M. Fawaz, John Hiscott2, and Rongtuan Lin (2006) Leukotriene A4 Hydrolase Expression in PEL Cells Is Regulated at the Transcriptional Level and Leads to Increased Leukotriene B4 Production J Immunol 2006; 176:7051-7061.
Wang Ju-Feng,Xiao W en-Bin (1993) Effects of lisinopril and captopril on calcium in rat heart, Acta Pharmacologica Sinica 14 (3)
Verjans, H.L., Cooke, B.A., de Jong, F.H., de Jong, CM.M. & van der Molen, H.J. (1973) Evaluation of a radioimmunoassay for testosterone estimation. Steroid Biochem. 4, 665-676.
Salmon, J.A., Simmons, P.M. and Moncada, S. (1983). The effects of BW 755C and other anti-inflammatory drugs on eicosanoid concentrations and leukocyte accumulation in experimentally induced acute inflammation. J. Pharm. Pharmacol., 35, 808-813.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186