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Nitric Oxide-Sensitive Guanylyl Cyclase Is Differentially Regulated by Nuclear and Non-Nuclear Estrogen Pathways in Anterior Pituitary Gland
BibTeX
@MISC{Cabilla_nitricoxide-sensitive,
author = {Jimena P. Cabilla and Silvana I. Nudler and Sonia A. Ronchetti and A A. Quinteros and Mercedes Lasaga and Beatriz H. Duvilanski},
title = {Nitric Oxide-Sensitive Guanylyl Cyclase Is Differentially Regulated by Nuclear and Non-Nuclear Estrogen Pathways in Anterior Pituitary Gland},
year = {}
}
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Abstract
17b-estradiol (E2) regulates hormonal release as well as proliferation and cell death in the pituitary. The main nitric oxide receptor, nitric oxide sensitive- or soluble guanylyl cyclase (sGC), is a heterodimer composed of two subunits, a and b, that catalyses cGMP formation. a1b1 is the most abundant and widely expressed heterodimer, showing the greater activity. Previously we have shown that E2 decreased sGC activity but exerts opposite effects on sGC subunits increasing a1 and decreasing b1 mRNA and protein levels. In the present work we investigate the mechanisms by which E2 differentially regulates sGC subunits ’ expression on rat anterior pituitary gland. Experiments were performed on primary cultures of anterior pituitary cells from adult female Wistar rats at random stages of estrous cycle. After 6 h of E2 treatment, a1 mRNA and protein expression is increased while b1 levels are down-regulated. E2 effects on sGC expression are partially dependent on de novo transcription while de novo translation is fully required. E2 treatment decreased HuR mRNA stabilization factor and increased AUF1 p37 mRNA destabilization factor. E2-elicited b1 mRNA decrease correlates with a mRNA destabilization environment in the anterior pituitary gland. On the other hand, after 6 h of treatment, E2-BSA (1 nM) and E2-dendrimer conjugate (EDC, 1 nM) were unable to modify a1 orb1 mRNA levels, showing that nuclear receptor is involved in E2 actions. However, at earlier times (3 h), 1 nM EDC causes a transient decrease of a1 in a PI3k-dependent fashion. Our results show for the first time that E2 is able to exert opposite actions in the anterior pituitary gland, depending
Keyphrases
anterior pituitary gland non-nuclear estrogen pathway nitric oxide-sensitive guanylyl cyclase differentially e2 treatment e2 effect mrna destabilization environment opposite action transient decrease sgc expression present work nm edc e2 action e2-elicited b1 mrna decrease protein level sgc subunit expression rat anterior pituitary gland hur mrna stabilization factor b1 mrna main nitric oxide receptor random stage nuclear receptor soluble guanylyl cyclase adult female wistar rat novo transcription primary culture pi3k-dependent fashion a1 mrna sgc subunit cell death opposite effect auf1 p37 mrna destabilization factor protein expression sgc activity anterior pituitary cell first time e2-dendrimer conjugate estrous cycle hormonal release a1 orb1 mrna level b1 level
