Effect of finasteride on behavioural arousal and somatosensory evoked potentials in fetal sheep.
This study examines the effect of inhibiting the synthesis of gamma-aminobutyric acid(A) (GABA(A)) agonist steroids on behavioural activity and somatosensory evoked potentials (SEP) in late gestation fetuses. Pregnane steroid production was suppressed by infusion of the 5alpha-reductase inhibitor, finasteride in chronically catheterised fetal sheep, 130-135 days gestation. Finasteride treatment (160 mg in 10 ml of vehicle over 2 h) significantly increased the incidence of fetal arousal during the period 4-10 h after commencing the infusion (P<0.05, n=6), whereas other behavioural parameters were not effected. In three of four animals, finasteride produced an increase in the amplitude of the N22 peak of the SEP during high voltage electrocortical activity. We conclude that suppression of pregnane steroid synthesis, by inhibition of the 5alpha-reductase enzyme, increases arousal activity in the fetus which is consistent with a reduction in GABA(A) receptor mediated inhibition.
Nicol
M B
MB
Department of Physiology, Monash University, Victoria 3168, Clayton, Australia.
Hirst
J J
JJ
Walker
D W
DW
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D018120:Finasteride / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011278:Pregnanes / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012756:Sheep; D013256:Steroids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D011278:Pregnanes; D011963:Receptors, GABA-A; D013256:Steroids; D005680:gamma-Aminobutyric Acid; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase