This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mancina, R. Articles by Maggi, M. Search for Related Content PubMed PubMed Citation Articles by Mancina, R. Articles by Maggi, M.

Identification, Characterization, and Biological Activity of Endothelin Receptors in Human Ovary¹

Department of Clinical Physiopathology, Andrology Unit (M.M., R.M., G.Fo.) and Endocrinology Unit (A.P.), Department of Human Anatomy and Histology (T.B., G.B.V.), Department of Pharmacology (S.A., S.F.), Department of Obstetrics and Gynecology (T.S.), University of Florence, 50139 Florence; and the First Department of Internal Medicine, Division of Andrology, University of Catania (A.C., N.B.), Catania 95123, Italy

Address all correspondence and requests for reprints to: Mario Maggi, M.D., Andrology Unit, Viale Pieraccini 6, 50139 Florence, Italy.

We previously reported the expression of endothelin-1 (ET-1) in granulosa cells (GCs) of the human ovary and the presence of ET-1-like immunoreactivity in human follicular fluid obtained from women in an in vitro fertilization program. In follicular fluid, but not in plasma, the levels of ET-1-like immunoreactivity were higher in gonadotropin-stimulated vs. spontaneous cycles, suggesting hormonal regulation of follicular ET-1. To identify and characterize ET receptors in human ovary, we performed autoradiography, radioligand binding, and functional studies. Mathematical analysis of families of self- and cross-competition curves among [¹²⁵I]ET-1, [¹²⁵I]ET-3, and selective analogs indicates that human ovary expresses both subtypes of ET receptors, i.e. ET_A and ET_B receptors. However, the concentration of the ET_B site was 100-fold lower than that of the ET_A one. By using [¹²⁵I]ET-1, we demonstrated that the density of binding sites in human ovary is not affected by the hormonal milieu (similar concentrations in normal cycling, postmenopausal, and combined oral contraceptive-treated women). In situ binding studies indicate that the majority of ET_A and ET_B receptors are expressed in the blood vessels of the ovary. In particular, ET_A receptors are abundant in the ovulatory follicles and localized in the theca interna, in close proximity to the granulosa layer. Few GCs of the ovulatory follicle were specifically labeled. Conversely, in the rat ovary, used as a control, ET_B receptors were predominantly expressed and localized in GCs. Accordingly, ET_B receptors negatively regulated estrogen accumulation in rat GCs. In human granulosa-luteal cells, neither ET-1 (unselective ligand) nor ET-3 or sarafotoxin 6c (ET_B ligands) affected estrogen or progesterone secretion. ET-1 was 2.5-fold more potent than noradrenaline in eliciting contraction of ovarian artery, acting through the ET_A receptor. Our results indicate that in human ovary, at variance with rat ovary, the endothelin system is primarily involved in the regulation of ovarian blood flow and not steroidogenesis.

This article has been cited by other articles:

				C. Boiti, G. Guelfi, G. Brecchia, C. Dall'Aglio, P. Ceccarelli, M. Maranesi, C. Mariottini, D. Zampini, A. Gobbetti, and M. Zerani Role of the Endothelin-1 System in the Luteolytic Process of Pseudopregnant Rabbits Endocrinology, March 1, 2005; 146(3): 1293 - 1300. [Abstract] [Full Text] [PDF]

				C. M. Komar and T. E. Curry Jr Localization and Expression of Messenger RNAs for the Peroxisome Proliferator-Activated Receptors in Ovarian Tissue from Naturally Cycling and Pseudopregnant Rats Biol Reprod, May 1, 2002; 66(5): 1531 - 1539. [Abstract] [Full Text]

				F. Miceli, F. Minici, M. G. Pardo, P. Navarra, C. Proto, S. Mancuso, A. Lanzone, and R. Apa Endothelins Enhance Prostaglandin (PGE2 and PGF2{{alpha}}) Biosynthesis and Release by Human Luteal Cells: Evidence of a New Paracrine/Autocrine Regulation of Luteal Function J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 811 - 817. [Abstract] [Full Text]

				J. A. Flores Gene Expression of Endothelin-1 in the Porcine Ovary: Follicular Development Biol Reprod, November 1, 2000; 63(5): 1377 - 1382. [Abstract] [Full Text]

				M. Maggi, T. Barni, G. Fantoni, R. Mancina, C. Pupilli, M. Luconi, C. Crescioli, M. Serio, and G. B. Vannelli Expression and Biological Effects of Endothelin-1 in Human Gonadotropin-Releasing Hormone-Secreting Neurons J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1658 - 1665. [Abstract] [Full Text]

				A. Plonowski, A. K.Kaplinski, M. Radzikowska, M. Borowiec, and B. Baranowska Correlation between 21 amino acid endothelin, intrafollicular steroids and follicle size in stimulated cycles Hum. Reprod., September 1, 1999; 14(9): 2323 - 2327. [Abstract] [Full Text] [PDF]

				P. Korth, R. M. Bohle, P. Corvol, and F. Pinet Cellular Distribution of Endothelin-converting Enzyme-1 in Human Tissues J. Histochem. Cytochem., April 1, 1999; 47(4): 447 - 462. [Abstract] [Full Text]

				A. Bagnato, D. Salani, V. Di Castro, J. R. Wu-Wong, R. Tecce, M. R. Nicotra, A. Venuti, and P. G. Natali Expression of Endothelin 1 and Endothelin A Receptor in Ovarian Carcinoma: Evidence for an Autocrine Role in Tumor Growth Cancer Res., February 1, 1999; 59(3): 720 - 727. [Abstract] [Full Text] [PDF]

				S. Yoshioka, H. Fujiwara, S. Yamada, K. Tatsumi, T. Nakayama, T. Higuchi, T. Inoue, M. Maeda, and S. Fujii Endothelin-Converting Enzyme-1 Is Expressed on Human Ovarian Follicles and Corpora Lutea of Menstrual Cycle and Early Pregnancy J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3943 - 3950. [Abstract] [Full Text]