Inhibition of testosterone production by propylthiouracil in rat Leydig cells.
Propylthiouracil (PTU) is a thioamide drug used clinically to inhibit thyroid hormone production. However, PTU is associated with some side effects in different organs. In the present study, the acute and direct effects of PTU on testosterone production in rat Leydig cells were investigated. Leydig cells were isolated from rat testes, and an investigation was performed on the effects of PTU on basal and evoked-testosterone release, the functions of steroidogenic enzymes, including protein expression of cytochrome P450 side-chain cleavage enzyme (P450(scc)) and mRNA expression of the steroidogenic acute regulatory protein (StAR). Rat Leydig cells were challenged with hCG, forskolin, and 8-bromo-cAMP to stimulate testosterone release. PTU inhibited both basal and evoked-testosterone release. To study the effects of PTU on steroidogenesis, steroidogenic precursor-stimulated testosterone release was examined. PTU inhibited pregnenolone production (i.e., it diminished the function of P450(scc) in Leydig cells). In addition to inhibiting hormone secretion, PTU also regulated steroidogenesis by diminishing mRNA expression of StAR. These results suggest that PTU acts directly on rat Leydig cells to diminish testosterone production by inhibiting P450(scc) function and StAR expression.
Department of Physiolog, School of Medicine, National Yang-Ming University, No. 155 Section 2, Li-nung Street, Taipei 11221, Taiwan, Republic of China.
Yu-Chung
YC
Chiao
Wen-Long
WL
Cho
Paulus S
PS
Wang
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D015153:Blotting, Western; D002469:Cell Separation; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis / Q000378:metabolism; D003864:Depression, Chemical; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism; D011284:Pregnenolone / Q000096:biosynthesis; D011441:Propylthiouracil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis; D013739:Testosterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
D000963:Antimetabolites; D006888:Hydroxycholesterols; D010750:Phosphoproteins; D012333:RNA, Messenger; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D013196:Dihydrotestosterone; D013739:Testosterone; D011441:Propylthiouracil; D011284:Pregnenolone; C007997:25-hydroxycholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; C009954:trilostane