Antiproliferative effects of inducible nitric oxide synthase inhibition on decidualization in pseudopregnant rats
| Autor: | Fitzgerald Spencer, Limen Chi, Ming-Xia Zhu |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Time Factors Blotting Western Nitric Oxide Synthase Type II Endogeny Endometrium Arginine Nitric Oxide General Biochemistry Genetics and Molecular Biology Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Decidua Animals Decidual cells Enzyme Inhibitors Pseudopregnancy Progesterone biology Estradiol Decidualization Metalloendopeptidases Metabolism Alkaline Phosphatase Rats Nitric oxide synthase Endocrinology medicine.anatomical_structure NG-Nitroarginine Methyl Ester chemistry biology.protein Myometrium Alkaline phosphatase Female Nitric Oxide Synthase Cell Division |
| Zdroj: | Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.). 218(1) |
| ISSN: | 0037-9727 |
| Popis: | The aim of this study was to assess the involvement in decidual proliferation of nitric oxide (NO), a regulator of many cellular processes, that is synthesized from L-arginine by NO synthase. The investigation was conducted on pseudopregnant (PG) rats in which the decidual cell reaction, the basis for the decidualization process, was surgically induced by uterine trauma on PG Day 4. Groups of animals (n = 5) were pretreated with either 2 doses/day of N(G)-nitro-L-arginine methyl ester (L-NAME) that inhibits NO synthase, or twice daily doses of L-NAME plus L-arginine combined. Drug application times coincided with 3 hr after lights on or 3 hr before lights off. The two treatment regimens (PG Days 1-4 or 5-8) respectively preceded or followed decidual induction. Animals were sacrificed at mid-light on PG Day 9, the day of maximal growth response to the deciduogenic stimulus. Parallel, time-dependent increases in both NO synthase activity and decidual growth occurred mainly in the endometrium. L-NAME produced reductions in endometrial and myometrial growth that were reversed by the combined L-NAME plus L-arginine treatments. These inhibitory effects by L-NAME were caused by only the pretraumal (PG Days 1-4) administration. Hormonally, circulating progesterone levels were similarly affected by this early treatment and may also contribute to the reduced decidual sensitivity. In contrast, serum estradiol, along with the zinc metalloenzymes, alkaline phosphatase and the matrix metalloproteinases--prominent decidualization biomarkers--were all unaffected by either the pre- or post-decidual induction dosings. The study demonstrates that inducible NO synthase/endogenous NO may physiologically participate in uterine metabolism during the decidual cell reaction. Moreover, by virtue of L-NAME inhibition of the decidual response, it appears that NO synthase/NO may influence decidual growth either by directly increasing uterine sensitivity to the deciduogenic stimulus or by indirectly affecting endometrial vascularity and subsequent availability of decidual metabolites. |
| Databáze: | OpenAIRE |
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