17β-Estradiol Modifies Nitric Oxide-Sensitive Guanylyl Cyclase Expression and Down-Regulates Its Activity in Rat Anterior Pituitary Gland

Abstract

Previous studies showed that 17β-estradiol (17β-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17β-E2 disrupts the inhibitory effect of NO on prolactin release, decreasing sGC activity and affecting the cGMP pathway in anterior pituitary gland of adult ovariectomized and estrogenized rats. To ascertain the mechanisms by which 17β-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17β-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17β-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing α1 and decreasing β1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6–9 h after 17β-E2 administration. 17β-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17β-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17β-E2, because they were not observed with the administration of other steroids such as progesterone and 17α-estradiol. This inhibitory action of 17β-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17β-E2 action. 17β-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17β-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC β1 subunit and sGC activity in a specific, ER-dependent manner.