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Estradiol 17-β and Progesterone Modulate Inducible Nitric Oxide Synthase and High Mobility Group Box 1 Expression in Human Endometrium

Department of Experimental Medicine, University La Sapienza, Rome, Italy

Chiara Centonze, MD

Department of Surgery, Section of Gynecology and Obstetrics, University Tor Vergata, Rome, Italy

Massimo Realacci, MD

Department of Experimental Medicine, University La Sapienza, Rome, Italy

Barbara Buchetti, PhD

Department of Experimental Medicine, University La Sapienza, Rome, Italy

Adalgisa Pietropolli, MD

Department of Surgery, Section of Gynecology and Obstetrics, University Tor Vergata, Rome, Italy

Carlo Ticconi, MD

Department of Surgery, Section of Gynecology and Obstetrics, University Tor Vergata, Rome, Italy, ticconi{at}med.uniroma2.it

The aim of the present study is to investigate the effects of ovarian sex steroid hormones on the expression and the release of several locally active substances by human endometrium. Specific objectives are (1) to ascertain if estradiol 17-β (E2) and progesterone modulate inducible nitric oxide synthase (iNOS) expression and nitric oxide release; (2) to determine whether human endometrium can express High Mobility Group Box 1 (HMGB1), a multifunctional cytokine, and whether sexual steroid hormones can modulate this expression; and (3) to evaluate whether nitric oxide can influence HMGB1 expression in this tissue. Endometrial tissue was obtained from 40 healthy premenopausal women who underwent hysteroscopy for suspected benign gynecological conditions. Endometrium was incubated with E2, progesterone, or sodium nitroprusside, a nitric oxide donor. Nitrite assay was used to quantify stable nitric oxide metabolites in culture medium, and Western blot analysis was used to detect iNOS and HMGB1. Incubation of endometrium with E2 results in an increase in iNOS expression and nitric oxide metabolite production. The opposite effect is obtained by incubating tissues with progesterone. HMGB1 is expressed by human endometrium, and its expression is increased by E2 and decreased by progesterone. Incubation with sodium nitroprusside results in a reduction in HMGB1 expression. Both E2 and progesterone modulate iNOS expression and nitric oxide production in human endometrium. HMGB1 is expressed in the human endometrium, and its expression is modulated by E2, progesterone, and nitric oxide.

Key Words: Endometrium • nitric oxide synthase • High Mobility Group Box 1 • estradiol • progesterone.

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