Effects of nitric oxide on ovulation and ovarian steroidogenesis and prostaglandin production in the rabbit.
Evidence supports the involvement of nitric oxide (NO) in ovarian physiology. The present study was undertaken to investigate the role of the NO/NO synthase (NOS) systems in ovulation, oocyte maturation, ovarian steroidogenesis, and PG production using in vitro perfused rabbit ovaries. The addition of the NOS inhibitors, aminoguanidine hemisulfate salt (AG) and N-omega-nitro-L-arginine methyl ester (L-NAME), to the perfusate inhibited the ovulation induced by hCG in a dose-dependent manner, whereas D-NAME had no significant effect. Neither AG nor L-NAME affected the hCG-induced meiotic maturation of the ovulated ova. The exogenous administration of the NO generator, sodium nitroprusside (NP), induced follicle rupture in the absence of gonadotropin, but did not induce oocyte maturation. Inhibition of endogenous NOS by AG and L-NAME resulted in a significant elevation in the production of estradiol (E2), but not of progesterone, stimulated by hCG. The concomitant administration of NP significantly reduced the AG-stimulated production of E2 by ovaries perfused in the presence of hCG, which suggests that NO down-regulates ovarian E2 synthesis. Ovarian production of PGE2 and PGF2alpha in response to hCG was significantly blocked by L-NAME, and exogenous administration of NP stimulated the production of PGs in the absence of gonadotropin. Significant correlations were observed between the ovulatory efficiencies and the production of PGs by rabbit ovaries perfused with or without L-NAME. In conclusion, the ovarian NO/NOS system is involved in follicle rupture during the ovulatory process. NO may induce follicle rupture in rabbit ovaries at least in part by the stimulation of PG production.
Yamauchi
J
J
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Miyazaki
T
T
Iwasaki
S
S
Kishi
I
I
Kuroshima
M
M
Tei
C
C
Yoshimura
Y
Y
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism*; D010060:Ovulation / Q000187:drug effects*; D011374:Progesterone / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D013256:Steroids / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D006146:Guanidines; D011453:Prostaglandins; D013256:Steroids; D009599:Nitroprusside; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester