The endogenous hydrogen sulfide generating system regulates ovulation.

The generation of free-radicals such as nitric oxide has been implicated in the regulation of ovarian function, including ovulation. Tissues that generate nitric oxide typically generate another free-radical gas, hydrogen sulfide (HS), although little is known about the role of HS in ovarian function. The hypothesis of this study was that HS regulates ovulation. Treatment with luteinizing hormone (LH) increased the levels of mRNA and protein of the HS generating enzyme cystathionine γ-lyase (CTH) in granulosa cells of mice and humans in vivo and in vitro. Pharmacological inhibition of HS generating enzymes reduced the number of follicles ovulating in mice in vivo and in vitro, and this inhibitory action was reversed by cotreatment with a HS donor. Addition of a HS donor to cultured mouse granulosa cells increased basal and LH-dependent abundance of mRNA encoding amphiregulin, betacellulin and tumor necrosis alpha induced protein 6, proteins important for cumulus expansion and follicle rupture. Inhibition of CTH activity reduced abundance of mRNA encoding matrix metalloproteinase-2 and -9 and tissue-type plasminogen activator, and cotreatment with the HS donor increased the levels of these mRNA above those stimulated by LH alone. We conclude that the HS generating system plays an important role in the propagation of the preovulatory cascade and rupture of the follicle at ovulation.