Evidence that hydrogen sulphide can modulate hypothalamo-pituitary-adrenalaxis function: In vitro and in vivo studies in the rat

The gas hydrogen sulphide (H2S) is normally produced in large amounts in th e central nervous system during the metabolism of sulphur-containing aminoa cidis. H2S was recently shown to influence long-term potentiation in the ra t hippocampus; this finding suggested that the gas may act as a neuromodula tor in the brain. We therefore tested the effect of the gas on the release of corticotropin-releasing hormone (CRH) from rat hypothalamic explants. CR H immunoreactivity in the incubation media was taken as a marker of peptide release, We found that the addition of NaHS to incubation media was consis tently associated with a concentration-dependent decrease in KCI-stimulated CRH release, whereas basal secretion was unaffected. Increased endogenous H2S production may be also obtained using an indirect precursor of H2S form ation, S-adenosyl-L-methionine (SAMe). The latter mimicked the effects of N aHS, since it reduced potassium-stimulated CRH release, In vivo, SAMe showe d no effect on hypothalamo-pituitary-adrenal (HPA) function under resting c onditions, but inhibited stress-related glucocorticoid increase.