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.
[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
[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
@article{"International Journal of Biological, Life and Agricultural Sciences:58274", author = "H. Sadi-Guettaf and F. Hadj Bekkouche", title = "Dexamethasone: Impact on Testicular Activity", 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 ", keywords = "Dexamethasone, FSH, LH, rat, testis, testosterone.", volume = "8", number = "7", pages = "662-4", }
