Neuro-steroids: 3 beta-hydroxy-delta 5-derivatives in rat and monkey brain.
The rat brain accumulates pregnenolone (P) as the unconjugated steroid, the sulfate ester (S) and fatty acid esters (L). P + PS do not disappear from rat brain after combined adrenalectomy (adx) and castration (orx). PL does not serve a source of P after adx + orx. P is metabolized by several rat brain regions to progesterone and to PL. Brain microsomes contain the acyl-transferase which converts P to PL using endogenous substrates. Brain P and dehydroepiandrosterone (D) undergo a prominent circadian variation with their acrophases at the beginning of the dark span. The circadian variation of brain D persists after adx + orx. The monkey brain (Macaca fascicularis) also accumulates P and D. Adrenal suppression with dexamethasone for 4 days does not decrease the concentrations of brain P and 3rd ventricle CSFP and D. The concentrations of brain D are decreased to a much smaller extent than plasma D. D inhibits the aggressive behavior of castrated male mice exposed to lactating female intruders. This is not the case for DS or androst-5-ene-3 beta, 17 beta-diol. The D analog 3 beta-methyl-androst-5-en-17-one, which is not estrogenic and cannot be metabolized to testosterone or estradiol, is as active as D in inhibiting the aggressive behavior of castrated mice.
D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D000315:Adrenalectomy; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002369:Castration; D002940:Circadian Rhythm; D003687:Dehydroepiandrosterone / Q000378:metabolism* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004952:Esters; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D011284:Pregnenolone / Q000378:metabolism*; D051381:Rats; D013431:Sulfates / Q000378:metabolism; D014018:Tissue Distribution
D004952:Esters; D005227:Fatty Acids; D005938:Glucocorticoids; D013431:Sulfates; D003687:Dehydroepiandrosterone; D011284:Pregnenolone; D003907:Dexamethasone