Nitric oxide modulates human chorionic gonadotropin-induced ovulation in the rabbit.
OBJECTIVE
To examine the potential role of the L-arginine:nitric oxide pathway in hCG-induced ovulation in the rabbit.


METHODS
Randomized, controlled animal study.


METHODS
University research laboratory.


METHODS
Nitric oxide synthase, the enzyme that produces nitric oxide (NO), was immunohistochemically localized in the ovary. NG-nitro-L-arginine methyl ester (L-NAME), an analogue of L-arginine, which inhibits the enzyme NO synthase, and the inactive D-enantiomer were administered in vivo and/or in vitro via an isolated, perfused ovary preparation during the periovulatory period.


METHODS
Rate of follicular rupture (ovulatory efficiency).


RESULTS
Immunohistochemical staining for NO synthase was localized specifically to the granulosa cell layer of the follicle and the endothelium and adventitia of ovarian blood vessels. In vivo administration of L-NAME significantly reduced the percentage of large follicles that ovulated in response to hCG (treated 24.6%, control 68.1%). Similarly, exposure of the in vitro-perfused ovary to L-NAME significantly reduced follicular rupture (treated 32.8%, control 64.2%). In contrast, addition of an equimolar concentration of D-NAME to the perfusion medium had no significant effect on the rate of ovulation (treated 83.3%, control 61.3%).


CONCLUSIONS
The stereospecific inhibition of follicular rupture by the arginine analogue suggests that NO production by the ovary is an important feature of the normal physiologic processes of the periovulatory period.
Hesla
J S
JS
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Preutthipan
S
S
Maguire
M P
MP
Chang
T S
TS
Wallach
E E
EE
Dharmarajan
A M
AM
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects*; D011817:Rabbits; D011897:Random Allocation; D013237:Stereoisomerism; D013997:Time Factors
D006063:Chorionic Gonadotropin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester