GONADOTROPIN-STIMULATED REGULATION OF BLOOD FOLLICLE BARRIER IS MEDIATED BY NITRIC-OXIDE

Although initially described over 30 years ago, the blood-follicle bar rier has remained a biological enigma. In this study, we characterize the blood-follicle barrier with respect to its regulation of intrafoll icular inter-alpha-trypsin inhibitor protein (I alpha I) influx after an ovulatory stimulus. We have found that I alpha I is localized withi n the ovarian vasculature but is excluded from the follicular compartm ent until an ovulatory stimulus is given. Within minutes after an ovul atory dose of human chorionic gonadotropin, I alpha I is localized wit hin the follicular fluid of responding follicles where this protein be comes associated with and stabilizes the newly synthesized hyaluronic acid-rich cumulus extracellular matrix. Analysis of this process has s hown that intravenous injection of sodium nitroprusside or excess subs trate for nitric oxide synthase, L-arginine, mimics the effect of gona dotropic hormones on the influx of I alpha I into the follicular compa rtment of preovulatory follicles. Moreover, intravenous injection of s pecific nitric oxide synthase inhibitors, N-G-nitro-L-arginine methyl ester and N-G-nitro-L-arginine, inhibits gonadotropin-mediated intrafo llicular influx of I alpha I and also inhibits ovulation in the mouse.