In vivo and in vitro effects of flutamide and diethylstilbestrol on fetal testicular steroidogenesis in the rat.
Prenatal testosterone surge is considered crucial for physiological masculinization of male progeny. Disorders in sex steroid hormone balance during the fetal development may interfere with male reproductive health later in life. In this study, we have investigated in utero and in vitro effects of flutamide (FLU) and diethylstilbestrol (DES) on fetal rat testicular steroidogenesis. In utero exposure to FLU 25mg/kg or DES 0.02mg/kg had no obvious effects on ED 19.5 rat testicular testosterone and progesterone production, StAR protein or AR protein expression. However, when ED 19.5 rat testis were cultured for 180min in the presence of 0.1, 1, 10 and 100mg/l of FLU or DES, the highest doses of both compounds were capable of disturbing steroidogenesis. To study the rate of the changes seen in testicular steroidogenesis after 180min, time-series experiments, in which intact testes were cultured with FLU 100mg/l or DES 100mg/l for 30, 60 or 120min, were performed. In vitro time-series experiments revealed that changes in steroidogenesis occur very fast. Experiments with FLU brought further evidence to the hypothesis that ARs have negative autocrine role in developing Leydig cells.
Adamsson
N Annika
NA
Department of Physiology, University of Turku, 20520 Turku, Finland.
Brokken
Leon J S
LJ
Paranko
Jorma
J
Toppari
Jorma
J
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D004054:Diethylstilbestrol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005485:Flutamide / Q000633:toxicity*; D005865:Gestational Age; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D000098682:Steroidogenic Acute Regulatory Protein
D000726:Androgen Antagonists; D004968:Estrogens, Non-Steroidal; D012739:Gonadal Steroid Hormones; D010750:Phosphoproteins; D011944:Receptors, Androgen; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D011374:Progesterone; D004054:Diethylstilbestrol; D005485:Flutamide