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Cyclic Expression of Endothelial Nitric Oxide Synthase mRNA in the Epithelial Glands of Human Endometrium

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Abstract

Objectives

Nitric oxide synthase (NOS), responsible for the synthesis of nitric oxide (NO), is the key enzyme that regulates the NO-mediated biologic functions in various types of tissue. We believed that NO may be involved in regulating the development of the microvascular system and vascular tone in human endometrium. However, the biology of NOS in this system remains poorly understood. To determine the paracrine action of NOS derived from endometrial cells on vascular blood flow, the first task is to identify NOS in endometrial cells. This study was undertaken to examine whether human endometrial cells would express endothelial or inducible NOS (eNOS or iNOS). In addition, we examined the cell-specific expression of eNOS.

Methods

Beta nicotinamide adenine dinucleotide reduced form (NADPH)-diaphorase histochemistry assay was carried out in human endometrial specimens (n = 4). Nitric oxide synthase mRNA expression was studied in intact tissue (n = 4), isolated epithelial glands (n = 25), and stromal cells (n = 10). Northern blot and solution hybridization/ribonudease protection assay with specific RNA probes transcribed from human eNOS and iNOS cDNA were used to identify NOS mRNAs.

Results

NADPH-diaphorase histochemistry selectively labeled epithelial glands in the late secretory phase. Northern blot analysis revealed that glandular cells expressed a single size of eNOS mRNA (4.5 kb) but no detectable iNOS. Endothelial NOS mRNA was expressed in epithelial glands, but it was not detectable in stromal cells. The relative amount of eNOS in epithelial glands isolated from specimens (n = 23) at various stages of menstrual cycle were analyzed using a solution hybridization assay. The levels of eNOS mRNA varied among specimens. Epithelial glands from early secretory endometrium showed greater expression of eNOS mRNA. The highest eNOS expression was found in the glands of late secretory endometrium. In contrast, iNOS was detected only in the epithelial glands of a menstrual endometrium.

Conclusion

This study demonstrated that NADPH-diaphorase activity is highly concentrated in the epithelial glands if late secretory endometrium. Expression of eNOS mRNA is enhanced in the glands of early secretory endometrium. The strongest expression resides in the epithelial glands of late secretory endometrium. This observation suggests that regulation of eNOS may be a physiologic response to steroid hormones and locally produced peptide hormones in the endometrial environment. It also suggests that NO may play a role in the onset of menses.

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Authors and Affiliations

  1. Departments of Obstetrics, Gynecology, and Reproductive Medicine, State University of New York at Stony Brook, Stony Brook, New York, 11794-809, USA

    Linda Tseng PhD, Jianhua Zhang MD, Tatyana Yu Peresleni PhD & Michael S. Goligorsky MD

Authors
  1. Linda Tseng PhD
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  2. Jianhua Zhang MD
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  3. Tatyana Yu Peresleni PhD
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  4. Michael S. Goligorsky MD
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Additional information

The investigation received financial support from the Special Programme of Research Development and Research Training in Human Reproduction, World Health Organization, no. 90116, and National Institutes of Health, USPHS grant HD-19247 to LT.

We thank the clinical staffs of the Departments of Obstetrics and Gynecology and Pathology at the State University of New York at Stony Brook, New York, and the physicians and pathologists at St. Charles Hospital, Port Jefferson, New York, for providing us with viable endometrial specimens and histologic diagnosis: Dr. Bloch and Dr Geller for providing eNOS and iNOS cDNA; Mr. J. Mazella for isolating and culturing endometrial cells; and Ms. Angela Sintchak for editing the manuscript.

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Tseng, L., Zhang, J., Peresleni, T.Y. et al. Cyclic Expression of Endothelial Nitric Oxide Synthase mRNA in the Epithelial Glands of Human Endometrium. Reprod. Sci. 3, 33–38 (1996). https://doi.org/10.1016/1071-5576(95)00039-9

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  • DOI: https://doi.org/10.1016/1071-5576(95)00039-9

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