The production of hydrogen sulfide is regulated by testosterone and S -adenosyl-l-methionine in mouse brain.

Hydrogen sulfide (H[sub 2]S) is endogenously produced in the brain from L-cysteine by the enzyme cystathionine β-synthase (CBS) and functions as a neuromodulator in the brain. H[sub 2]S selectively enhances NMDA receptor-mediated responses and alters hippocampal long-term potentiation (LTP). The production of H[sub 2]S is regulated by Ca[sup 2+]/calmodulin-mediated pathways and is enhanced in response to neuronal excitation. In addition to this fast regulation, we describe here a slower form of the regulation of H[sub 2]S production by testosterone and S-adenosyl-L-methionine (SAM), a CBS activator. Endogenous H[sub 2]S in the mouse brain increases after birth, reaches a maximum level at 8 weeks and then decreases. Female brain contains less H[sub 2]S than male brain at each age. A single administration of testosterone to female mice increases the endogenous H[sub 2]S and SAM, which reach levels similar to those of male mice. In contrast, castration of male mice decreases the levels of testosterone, SAM and H[sub 2]S in the brain. Administration of SAM once a day for 3 days increases the brain H[sub 2]S without significantly changing the testosterone level. These observations suggest that testosterone can regulate the brain H[sub 2]S level via changing the level of SAM. [ABSTRACT FROM AUTHOR]