Dexamethasone: Impact on Testicular Activity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 33122
Dexamethasone: Impact on Testicular Activity

Authors: H. Sadi-Guettaf, F. Hadj Bekkouche

Abstract:

Dexamethasone (Dex) is a synthetic glucocorticoid that is used in therapy. However prolonged treatments with high doses are often required. This causes side effects that interfere with the activity of several endocrine systems, including the gonadotropic axis. The aim of our study is to determine the effect of Dex on testicular function in prepubertal Wistar rats. Newborn Wistar rats are submitted to intraperitoneal injection of Dex (1μg of Dex dissolved in NaCl 0.9% / 5g bw) for 20 days and then sacrificed at the age of 40days. A control group received NaCl 0.9%. The rat is weighed daily. The plasmatic levels of testosterone, LH and FSH were measured by radioimmunoassay. A histomorphometric study was performed on sections of testis. Treated groups showed a significant decrease in body weight (p < 0.05), testis weight (p < 0.05) and plasma levels of testosterone (p < 0.05), of LH (P < .05) and FSH (p> 0.05). There is a reduction of seminiferous tubules average diameter and also of the seminiferous epithelium thickness with an increasing of lumen tubular. The diameter of the Leydig cells and Sertoli cell nucleus is also significantly reduced. Spermatogenesis is blocked at the stage round spermatid unlike witnesses or elongated spermatid stage is found. These results suggest that Dex administered during neonatal life influences testicular activity in the long term.

Keywords: Dexamethasone, FSH, LH, rat, testis, testosterone.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1094501

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References:


[1] S.K. Guthrie, M. Heidt, A. Pande, "A longitudinal evaluation of dexamethasone pharmacokinetics in depressed patients and normal controls,” J Clin Psychopharmacol, vol.12, pp.191–196, 1992.
[2] C. Queckenberg, B. Wachall, V. Erlinghagen, P. Paola Di Gion, D. Tomalik-Scharte, M. Mona Tawab, K. Gerbeth, and U. Fuhr, "Pharmacokinetics, Pharmacodynamics, and Comparative Bioavailability of Single, Oral 2-mg Doses of Dexamethasone Liquid and Tablet Formulations: A Randomized, Controlled, Crossover Study in Healthy Adult Volunteers,” Clinical Therapeutics, vol.33, pp.183- 1841, 2011.
[3] J.W. Findling, H. Raff, D.C. Aron, "The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing’s syndrome,” J Clin Endocrinol Metab, vol.89, pp.1222–1226, 2004 .G. O. Young, "Synthetic structure of industrial plastics (Book style with paper title and editor),” in Plastics, 2nd ed. vol. 3, J. Peters, Ed. New York: McGraw- Hill, 1964, pp. 15–64.
[4] K.. O'Brien, H. Sekimoto, C. Boney, M. Malee, "Effect of fetal dexamethasone exposure on the development of adult insulin sensitivity in a rat model”, J. Matern. Fetal Neonatal Med., vol.21, pp. 623–628, 2008.W.-K. Chen, Linear Networks and Systems (Book style). Belmont, CA: Wadsworth, 1993, pp. 123–135.
[5] J.R. Seck, "Glucocorticoid programming of the fetus: adult phenotypes and molecular mechanisms”, Mol Cell Endocrinol, vol 185, pp. 61–71, 2001.
[6] American Academy of Pediatrics, "Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia.Committee on Fetus and Newborn,” Pediatrics, vol.126, pp.800, 2010.
[7] S.G. Matthews, D. Owen, S. Banjanin, M.H. Andrews, "Glucocorticoids, hypothalamo-pituitary-adrenal (HPA) development, and life after birth” Endocr Res,vol. 28,pp.709–718, 2002.
[8] A.E. Calogero, T.C. Kamillaris, E.O. Johnson, M.E. Tartagila and G. Chrousos, "Recovery of the rat hypothalamic- pituitary –adrenal axix after discontinuation of prolonged treatment with the synthetic glucocorticoid agonist dexamethasone”, Endocrinol., vol. 127, pp. 1574- 1579, 1990.
[9] F.M. Tomas, "The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone,” Journal of endocrinology, vol. 157, 89-97, 1998.
[10] D.L. Tempel, S.F. Leidowitz, "Adrenal steroid receptors: interactions with brain neuropeptide systems in relation to nutrient intake and metabolism,”,J Neuroendocrinol., vol.6,pp. 479-501, 1994.
[11] S. Wetzter, V. Dumaz, M. Goubern, D. Tomé, and C. Larue-Achagiotis, "Intraperitoneal leptin RL modifies macronutrient choice in selfselecting rats,” Physiol Behav., vol. 83, pp. 65-72, 2004.
[12] K.E. Orwig , B.Y. Ryu, M.R.. Avarbock, and Brinster, "Male germ-line stem cell potential is predicted by morphology of cells in neonatal rat testes” PNAS.,vol. 93, pp.11706-11711 , 2002.
[13] S.M.L. Chamindrani Mendis-Handagama and H.B. Siril Ariyaratne, "Differentiation of the adult Leydig cell population in the postnatal testis”, Biology of reproduction, vol.65, pp. 660-667, 2001.
[14] Q. Dong, A. Salva, C.M. Sottas , E. Niu, M. Holmes , M.P. Hardy, "Rapid glucocorticoid mediation of suppressed testosterone biosynthesis in male mice subjected to immobilization stress”. Journal of andrology , vol. 25,pp. 973-981, 2004
[15] M.P. Hardy, H.B. Gao, Q. Dong , R. Ge , Q. Wang, W.R. Chai, X. Feng, and C. Sottas "Stress hormone and male reproductive function” Cell and Tissu Research, vol. 322, pp. 147-153, 2005.
[16] G. Biagini, E. Merlo Pich, A. Frasoldati, L.F. Agnati and P. Marrama, "Changes in glucocorticoid receptor immunoreactivity after adrenalectomy and corticosterone treatment in the rat testis,” J Endocrinol Invest, vol.18, pp. 384-390, 1995.
[17] M.A. Weber , S. Groos, U. Hὅpfl, M. Spielmann, G. Aumüller, L. Konrad, "Glucocorticoid receptor distribution in testis during postnatal development and effects of dexamethasone on immature peritubular cells in vitro,” Andrologia, vol.32, pp. 23-30, 2000.
[18] F.O. Levy, A.H. Ree, L. Eikvar, M.V. Govindan, T. Jahnsen, V. Hansson, "Glucocorticoid receptors and glucocorticoid effects in rat Sertoli cells,” Endocrinol, vol.124, pp. 430-436, 1988.
[19] S. Banjanin, A. Kapoor and S.G. Matthews "Prenatal glucocorticoid exposure alters hypothalamic–pituitary–adrenal function and blood pressure in mature male guinea pigs,” J Physiol, vol., 558, pp. 305–318, 2004.
[20] D.M. Sloboda, T.J. Moss, S. Li, D. Doherty, I. Nitsos, J.R. Challis, "Prenatal betamethasone exposure results inpituitary-adrenal hyporesponsiveness in adult sheep,” Am J Physiol Endocrinol Meta.,vol 292, pp. 61–70, 2007.
[21] R. Badrinarayanan, S. Rengarjan, P. Nthya, K. Balasubramanian . "Corticosterone impairs the mRNA expression and activity of 3β and 17β hydroxysteroid dehydrogenases in adult rat Leydig cells,” Biochemestry and cell biology, vol. 84, pp.745-754, 2006.
[22] L.D.B. Hales and A.H. Payne, "Glucocorticoid-mediated repression of P450scc Mrna and de novo synthesis in cultured Leydig cells,” Endocrinology, vol, 124, pp.2099-2104, 1989.
[23] A.H. Payne and L.L. Sha, " Multiple mechanisms for regulation of 3β- hydroxy steroid dehydrogenase /delta5 delta4 isomerase, 17 alpha hydroxylase/C17-20lyase cytochrome P450, P450 messenger ribonucleic acid levels in primary cultures of mouse Leydig cells,” Endocrinology, vol. 129, pp.1429-1435,1991.
[24] A.M. Leal, A.L. Blount, C.J. Donaldson , M. Bilezikjian, W.W. Vale, " Regulation of follicle stimulating hormone secretion by the interaction of activinA, dexamethasone and testosterone in anterior pituitary cell cultures of male rats” Neuro. Endocrinol. , vol. 77, pp. 298-305, 2003.
[25] Ristic, Natasa Nestorovic, Milica Manojlovic-Stojanoski, Ivana Medigovic,Svetlana Trifunovic, BrankaSosic-Jurjevic, Verica Milosevic, "Exposure to dexamethasone reduces pituitary volume