Endocrinology, Vol 137, 3101-3110, Copyright © 1996 by Endocrine Society

ARTICLES

Diabetes-mediated decreases in ovarian superoxide dismutase activity are related to blood-follicle barrier and ovulation defects

RW Powers, C Chambers and WJ Larsen
Developmental Biology, University of Cincinnati College of Medicine, Ohio 45267, USA.

The activity of nitric oxide (NO) has been implicated as an important mediator in ovarian function, including the regulation of the blood- follicle barrier and ovulation. Both clinical and experimental diabetes have been found to impair endothelial-dependent vascular activity through the inactivation of NO. It has also been shown that diabetes- induced inactivation of NO can be rescued with administration of insulin as well as with free radical scavengers such as superoxide dismutase (SOD). In this study, we report decreases in both ovulation and the activity of the blood-follicle barrier in insulin-dependent diabetic prepubertal mice treated with exogenous gonadotropic hormones. Moreover, these ovarian defects are rescued with administration of insulin, nitroprusside, L-arginine, and the free radical scavengers citiolone and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron). We found that the activity of Cu/Zn SOD in the ovaries of diabetic mice used in this study is decreased by 48% compared to that in nondiabetic mice. In contrast, inhibition of SOD activity in nondiabetic mice induces defects in the blood-follicle barrier and ovulation similar to those observed in diabetic mice. Lastly, we report the localization of endothelial nitric oxide synthase, inducible NOS, Cu/Zn SOD, and the LH receptor to the same population of endothelial cells surrounding the preovulatory follicle, supporting our hypothesis that the signaling of ovarian NO within the ovarian microvasculature at the time of ovulation may be compromised in these diabetic mice as a consequence of the loss of the protective activity of Cu/Zn SOD.

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