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

The expression of arginine-vasopressin (AVP) is regulated by estradiol and testosterone (T) indifferent 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 beta in the regulation of AVP expression exerted by T via its metabolite 5 alpha-dihydrotestosterone (5 alpha-DHT) and its further conversion in the androgen metabolite and ER beta ligand 3 beta-diol. In this study we have explored the role of ERs in the regulation exerted by estradiol and T on AVP expression, using the human neuroblastoma cell line SH-SY5Y. Estradiol treatment increased AVP mRNA levels in SH-SY5Y cells in comparison with cells treated with vehicle. The stimulatory effect of estradiol on AVP expression was imitated by the ER alpha agonist 4,4',4',-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol and blocked by the ER antagonist, ICI 182,780, and the ER alpha antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1hpyrazoledihydrochloride. In contrast, the ER beta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile reduced AVP expression, whereas the ER beta antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol enhanced the action of estradiol on AVP expression. T increased AVP expression in SH-SY5Y cells by a mechanism that was dependent on aromatase but not on 5 alpha-reductase activity. The T effect was not affected by blocking the androgen receptor, was not imitated by the T metabolite 5 alpha-DHT, and was blocked by the ER alpha antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1hpyrazoledihydrochloride. In contrast, 5 alpha-DHT had a similar effect as the ER beta agonists 2,3-bis(4-hydroxyphenyl)-propionitrile and 3 beta-diol, reducing AVP expression. These findings suggest that estradiol and T regulate AVP expression in SH-SY5Y cells through ERs, exerting a stimulatory action via ER alpha and an inhibitory action via ER beta.