Transient inhibitory effect of methoxychlor on testicular steroidogenesis in rat: an in vivo study.
Methoxychlor, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male reproductive tract. To get more insight into the mechanism(s) of gonadal toxicity provoked by methoxychlor, we investigated whether treatment with methoxychlor at low observed adverse effect level (LOAEL) would alter the activities of steroidogenic enzymes such as Delta(5)3beta-hydroxysteroid dehydrogenase (3beta-HSD) and Delta(5)17beta-hydroxysteroid dehydrogenase (17beta-HSD), the expression levels of steroidogenic acute regulatory (StAR) protein and androgen binding protein (ABP) in the testis of adult male rats. The experimental rats were exposed to a single dose of methoxychlor (50 mg/kg body weight) orally. The rats were killed at 0, 3, 6, 12, 24 and 72 h following treatment using anesthetic ether and testes were collected, processed and used to measure the activities of 3beta-HSD, 17beta-HSD, levels of hydrogen peroxide produced and the expression levels of StAR protein, and ABP. Methoxychlor administration resulted in a sequential reduction in the expression of StAR protein and activities of 3beta-HSD, 17beta-HSD with concomitant increase in the levels of hydrogen peroxide in the testis. These changes were significant between 6-12 h following treatment. The levels of ABP declined at 6-12 h following exposure to methoxychlor. The present study demonstrates transient effect of methoxychlor at LOAEL on testicular steroidogenesis and the possible role of hydrogen peroxide in mediating these effects.
Vaithinathan
S
S
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
Saradha
B
B
Mathur
P P
PP
D015067:17-Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000727:Androgen-Binding Protein / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008731:Methoxychlor / Q000008:administration & dosage / Q000633:toxicity*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
D000727:Androgen-Binding Protein; D007306:Insecticides; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D006861:Hydrogen Peroxide; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D008731:Methoxychlor