ECE2007 Oral Communications Reproductive endocrinology I (7 abstracts)
Estrogens regulate epididymal contractility through RhoA/Rho-kinase signaling
Sandra Filippi 3 , Annamaria Morelli 1 , Linda Vignozzi 1 , Rosa Mancina 1 , Sara Mungai 1 , Stefano Ambrosini 4 , Gabriella Barbara Vannelli 4 , Gianni Forti 2 & Mario Maggi 1
1University of Florence, Department of Clinical Physiopathology, Andrology Unit, Florence, Italy; 2University of Florence, Department of Clinical Physiopathology, Endocrinology Unit, Florence, Italy; 3University of Florence, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Dept. of Pharmacology and Clinical Physiopathology, Florence, Italy; 4University of Florence, Department of Anatomy, Histology and Forensic Medicine, Florence, Italy.
Epididymis (epi) is a sex steroid-sensitive duct provided with spontaneous motility, allowing sperm transport. We previously demonstrated that human epi expresses a high abundance of mRNA for ER-alpha and ER-beta. We demonstrated that in epi estrogens up-regulate either oxytocin (OT) responsiveness, acting at the receptor level, and responsiveness to endothelin-1 (ET-1), another well-known stimulator of epididymal motility. However, we did not find any significant change either at gene or protein level in ET-1 and its receptors. Hence, other molecular effectors should mediate the increased sensitivity to ET-1. In particular we hypothesized that estrogens up-regulate some contractile effectors, such as RhoA/Rho-kinase pathway, downstream to the ET-1 receptors. To investigate the effect of changing endocrine milieu on RhoA/Rho-kinase pathway, we induced hypogonadism (hypo) in rabbits with a single administration of a long-acting GnRH analog, triptorelin, and we replaced weekly hypo rabbits with different sex steroids (Testosterone, T or estradiol valerate, E2). After 8 weeks from GnRH analog administration, T plasma levels were decreased and the relaxant effect of the Rho-kinase inhibitor, Y-27632 on ET-1 pre-contracted epididymal strips, was significantly decreased. T administration restored T plasma levels, but not Y-27632 sensitivity in the epididymal strips. E2 not only completely restored Y-27632 responsiveness but even amplified it, as indicating that the RhoA/Rho-kinase calcium sensitizing pathway is up-regulated by E2. Accordinly, real time RT-PCR studies, western blot and immunohistochemistry analysis indicate that Rho kinase gene and protein was induced by E2 but not by T. To verify whether endogenous estradiol is involved in the regulation of Y-27632 responsiveness, we treated intact rabbits with an aromatase inhibitor, letrozole. Blocking aromatase activity abolished Y-27632 responsiveness in epi. In conclusion, our results support the hypothesis that epi is a male target for E2, which regulates its motility tuning up contractile hormones and local peptides responsiveness by increasing RhoA/Rho-kinase signalling and therefore calcium sensitivity.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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