5 alpha-dihydrotestosterone has nonspecific effects on membrane channels and possible genomic effects on ACh-activated channels.
1. Myotubes cultured from adult male Xenopus laevis laryngeal muscle have been found to express androgen receptors. 2. Using patch-clamp techniques, it was found that 5 alpha-dihydrotestosterone (5 alpha-DHT) can act directly at membranes of these myotubes to alter the kinetic properties of acetylcholine- (ACh) activated single channels. 3. When the culture medium contains 5 alpha-DHT for greater than 6 days, the androgen acts through its receptors to markedly increase ACh-activated, single-channel conductances and alter single-channel kinetics. These effects do not occur if the antiandrogen, flutamide, which prevents the androgen from combining with its receptor, is added to the medium before the addition of the 5 alpha-DHT. These effects also do not occur in myotubes cultured from quadriceps femoris muscles that have much lower levels of specific androgen receptor. 4. When alpha-bungarotoxin (alpha-BTX) is added to the medium for 3 h before recording, no ACh channels can be recorded from myotubes in control medium within 5 h after washout of the alpha-BTX. However, when the culture medium contains 5 alpha-DHT for greater than or equal to 6 days, ACh channels can be recorded within 8 min of the washout of the alpha-BTX. 5. The results suggest that 5 alpha-DHT may act to alter the properties of ACh-activated ion channels at multiple sites in excitable cells.
Erulkar
S D
SD
Department of Pharmacology, University of Pennsylvania Medical School, Philadelphia 19104.
Wetzel
D M
DM
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002038:Bungarotoxins / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000378:metabolism; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology*; D005485:Flutamide / Q000494:pharmacology; D006651:Histocytochemistry; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000502:physiology; D009928:Organ Specificity; D011944:Receptors, Androgen / Q000378:metabolism*; D014316:Tritium; D014982:Xenopus laevis
D002038:Bungarotoxins; D007473:Ion Channels; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D014316:Tritium; D005485:Flutamide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000109:Acetylcholine