Estradiol and Testosterone Regulate Arginine-Vasopressin Expression in SH-SY5Y Human Female Neuroblastoma Cells Through Estrogen Receptors-α and -β

Abstract

The expression of arginine-vasopressin (AVP) is regulated by estradiol and testosterone in different neuronal populations by mechanisms that are not yet fully understood. Estrogen receptors (ERs)have been shown to participate in the regulation of AVP neurons by estradiol. In addition, there is evidence of the participation of ER in the regulation of AVP expression exerted by testosterone via its metabolite 5- alpha-dihyihydrotestosterone (5-alpha DHT) and its further conversion in the androgen metabolite and ER ligand 3-diol. In this study we have explored the role of ERs in the regulation exerted by estradiol and testosterone on AVP expression, using the human neuroblastoma cell line SH-SY5Y. Estradiol treatment increased AVP mRNA levels in SH-SY5Y cells in comparison to cells treated with vehicle. The stimulatory effect of estradiol on AVP expression was imitated by the ER agonist PPT and blocked by the ER antagonist, ICI 182,780 and the ER antagonist MPP. In contrast, the ER beta agonist DPN reduced AVP expression, while the ER antagonist PHTPP enhanced the action of estradiol on AVP expression. Testosterone increased AVP expression in SH-SY5Y cells by a mechanism that was dependent on aromatase, but not on 5-reducatse activity. testosterone effect was not affected by blocking androgen receptor, was not imitated by the testosterone metabolite 5-DHT, and was blocked by the ER alpha antagonist MPP. In contrast, 5-alpha-DHT had a similar effect than the ER beta agonists DPN and 3-beta-diol, reducing AVP expression. These findings suggest that estradiol and testosterone regulate AVP expression in SH-SY5Y cells through ERs, exerting a stimulatory action via ER alpha and an inhibitory action via ER beta