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ToxSci Advance Access published online on March 14, 2006

Toxicological Sciences, doi:10.1093/toxsci/kfj156
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received November 28, 2005
Accepted February 20, 2006

Environmental Toxicology

Effects of Neonatal Exposure to 4-tert-octylphenol, Diethylstilbestrol, and Flutamide on Steroidogenesis in Infantile Rat Testis

Tiina F. M. Mikkilä 1, Jorma Toppari 2, and Jorma Paranko 3 *

1 Department of Biology, Laboratory of Animal Physiology, University of Turku, 20520 Turku, Finland
2 Departments of Physiology and Pediatrics, University of Turku, 20520 Turku, Finland
3 Department of Anatomy, University of Turku, 20520 Turku, Finland

* To whom correspondence should be addressed.
Jorma Paranko, E-mail: paranko{at}utu.fi


   Abstract

Exposure of neonatal testis, populated by fetal-type Leydig cells, to endocrine active compounds may have far-reaching consequences. Our aim was to resolve the sensitivity of testosterone synthesis of infant rat (Sprague Dawley) testis to diethylstilbestrol (DES; 0.1-1.0 mg/kg), 4-tert-octylphenol (OP; 10-100 mg/kg), and Flutamide (FLU; 2.0-25 mg/kg) given by daily subcutaneous injections from birth to postnatal day 4. Testes and serum were collected on day 14 when body and testis weight, testicular histology, circulating testosterone, LH and FSH levels, StAR and 3{beta}-HSD protein levels were determined. DES at each dose and FLU at 25 mg/kg dose reduced testis weight and the diameter of seminiferous cords. FLU caused some Leydig cell hyperplasia. Plasma testosterone was reduced in all DES animals, LH elevated in DES 0.5 mg/kg and FLU 25 mg/kg animals, FSH reduced in the DES 1.0 mg/kg group. Basal testicular ex vivo progesterone and hCG-stimulated testosterone production were decreased in DES animals. Despite a decrease in hCG-induced cAMP production, intratesticular testosterone was increased in the FLU 10 and 25 mg/kg groups. OP 100 mg/kg elevated hCG-induced progesterone production only. No changes were seen in 3{beta}-HSD protein levels in any treatment group. StAR levels were reduced in DES animals. The results indicate the sensitivity of postnatal fetal-type Leydig cells to endocrine active compounds. Suppression of StAR expression level was an early sign of the DES-induced steroidogenic lesion. FLU-induced changes suggest the importance of androgen receptor-mediated regulation of testosterone synthesis in the postnatal rat testis. Octylphenol appeared less effective in bringing about acute steroidogenic changes.

Keywords: diethylstilbestrol; octylphenol; Flutamide; testosterone; rat; testis; endocrine disruption.
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