Upregulation of peripubertal rat Leydig cell steroidogenesis following 24 h in vitro and in vivo exposure to atrazine.
Atrazine is currently one of the most widely used herbicides in the United States and elsewhere. Here we examined 24 h in vitro and in vivo effects of atrazine on androgen production and on expression and activity of steroidogenic enzymes and regulatory proteins involved in cyclic adenosine monophosphate (cAMP)-signaling pathway in peripubertal rat Leydig cells. When in vitro added, 1-50 μM atrazine increased basal and human chorion gonadotropin-stimulated testosterone production and accumulation of cAMP in the medium of treated cells. The stimulatory action of atrazine on androgen production but not on cAMP accumulation was abolished in cells with inhibited protein kinase A. Atrazine also stimulated the expression of mRNA transcripts for steroidogenic factor-1, steroidogenic acute regulatory protein, cytochrome P450 (CYP)17A1, and 17β-hydroxysteroid dehydrogenase (HSD), as well as the activity of CYP17A1 and 17βHSD. The stimulatory effects of atrazine on cAMP accumulation and androgen production were also observed during the first 3 days of in vivo treatment (200 mg/kg body weight, by gavage) followed by a decline during further treatment. These results indicate that atrazine has a transient stimulatory action on cAMP signaling pathway in Leydig cells, leading to facilitated androgenesis.
Pogrmic-Majkic
Kristina
K
Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia.
Fa
Svetlana
S
Dakic
Vanja
V
Kaisarevic
Sonja
S
Kovacevic
Radmila
R
D000728:Androgens / Q000378:metabolism; D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000235:genetics / Q000378:metabolism*; D006540:Herbicides / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000098682:Steroidogenic Acute Regulatory Protein
D000728:Androgens; D012739:Gonadal Steroid Hormones; D006540:Herbicides; D010750:Phosphoproteins; D054339:Steroidogenic Factor 1; D013778:Tetrazolium Salts; D013844:Thiazoles; D000098682:Steroidogenic Acute Regulatory Protein; C515060:steroidogenic factor 1, rat; D013739:Testosterone; D011374:Progesterone; D000242:Cyclic AMP; D013254:Steroid 17-alpha-Hydroxylase; C022616:thiazolyl blue; D001280:Atrazine