Modulatory action of 5-reduced androgens and progestins on the excitability of CNS and smooth muscle.
A hypothesis is proposed for the physiological role of the many 5 alpha and 5 beta-reduced metabolites of both testosterone and progesterone. The effects of 5-reduced steroids are observed mostly in excitable tissues. The outstanding effects are depression of neuronal activity, inhibition of neurotransmitters and smooth muscle relaxation. A clear chemical-structure-biological-activity relationship is observed. Thus, 5 beta-progestins are the most prominent, whereas 5 alpha-3-keto compounds are practically ineffective. An intermediate effect is observed with the delta 4 precursors and compounds with the configuration 3 alpha-hydroxy-5 alpha. Membranal stabilization and a Ca2+ antagonism are proposed as mechanisms of action. The main conclusion is that testosterone and progesterone are pre-hormones in the membranal effects of 5-reduced steroids. Likewise, these compounds participate in the cellular control of calcium influx, thereby modulating excitability in general.
Kubli-Garfias
C
C
Unidad de Investigación Biomédica, Instituto Mexicano del Seguro Social, México, D.F.
D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003864:Depression, Chemical; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011247:Pregnancy; D011278:Pregnanes / Q000494:pharmacology*; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*; D014590:Uterine Contraction / Q000187:drug effects
D000731:Androstanes; D011278:Pregnanes; D002118:Calcium