17 beta-estradiol modifies nitric oxide-sensitive guanylyl cyclase expression and down-regulates its activity in rat anterior pituitary gland.
Previous studies showed that 17 beta-estradiol (17 beta-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17 beta-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 17 beta-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17 beta-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17 beta-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing alpha1 and decreasing beta1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6-9 h after 17 beta-E2 administration. 17beta-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17 beta-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17 beta-E2, because they were not observed with the administration of other steroids such as progesterone and 17 alpha-estradiol. This inhibitory action of 17beta-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17 beta-E2 action. 17 beta-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17 beta-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC beta 1 subunit and sGC activity in a specific, ER-dependent manner.
Cabilla
Jimena P
JP
Departamento de Química Biológica, Instituto de Química y Fisico Química Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires (C1113AAD), Argentina.
Díaz
María del Carmen
Mdel C
Machiavelli
Leticia I
LI
Poliandri
Ariel H
AH
Quinteros
Fernanda A
FA
Lasaga
Mercedes
M
Duvilanski
Beatriz H
BH
D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D006162:Guanylate Cyclase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology; D012995:Solubility
D007527:Isoenzymes; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D006162:Guanylate Cyclase; D006152:Cyclic GMP