The effects of cytochalasin B on testosterone synthesis by interstitial cells of rat testis.
The present study examined the effects of cytochalasin B on various steps in the luteinizing hormone (LH)-stimulated increase in testosterone synthesis by collagenase-dispersed interstitial cells of adult rat testis. Cytochalasin B at a concentration range of 0.1--50 microM inhibited the LH-stimulated increase in testosterone synthesis in a dose-dependent manner. Both intracellular and medium (released) testosterone levels were reduced, thus indicating that the decrease was not due to the accumulation of testosterone inside the cell as a result of cytochalasin B treatment. Cytochalasin B also inhibited the 8-bromocyclic AMP and pregnenolone-stimulated testosterone synthesis in a similar dose-dependent manner. Cytochalasin B at the two higher doses (10 and 50 microM) also inhibited the LH-stimulated generation of cyclic AMP by interstitial cells. However, this drug had no effect on basal testosterone synthesis except at the highest concentration added. Previous studies on adrenocorticotropic hormone (ACTH)- and LH-stimulated increase in glucocorticoid and testosterone synthesis in adrenal and Leydig cells, respectively, demonstrated that cytochalasin B or anti-actin inhibited the transport of cholesterol into mitochondria. The present studies suggest that cytochalasin B inhibits at least two additional steps in the LH-stimulated increase in testosterone synthesis: (1) the generation of cyclic AMP at the level of the plasma membrane, and (2) the conversion of pregnenolone to testosterone at the level of the smooth endoplasmic reticulum. It remains to be established whether these are direct effects of cytochalasin B, or whether they are mediated by disruption of microfilaments by cytochalasin B.
D015124:8-Bromo Cyclic Adenosine Monophosphate; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D013739:Testosterone / Q000096:biosynthesis*
D015124:8-Bromo Cyclic Adenosine Monophosphate; D003571:Cytochalasin B; D013739:Testosterone; D011284:Pregnenolone; D007986:Luteinizing Hormone; D000242:Cyclic AMP