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Am J Physiol Endocrinol Metab 296: E731-E737, 2009. First published January 13, 2009; doi:10.1152/ajpendo.90795.2008
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Nitric oxide sensitive-guanylyl cyclase subunit expression changes during estrous cycle in anterior pituitary glands

Jimena P. Cabilla, Sonia A. Ronchetti, Silvana I. Nudler, Eliana A. Miler, Fernanda A. Quinteros, and Beatriz H. Duvilanski

Departamento de Química Biológica, Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

Submitted 6 September 2008 ; accepted in final form 7 January 2009

17β-Estradiol (E2) exerts inhibitory actions on the nitric oxide pathway in rat adult pituitary glands. Previously, we reported that in vivo E2 acute treatment had opposite effects on soluble guanylyl cyclase (sGC) subunits, increasing {alpha}1- and decreasing β1-subunit protein and mRNA expression and decreasing sGC activity in immature rats. Here we studied the E2 effect on sGC protein and mRNA expression in anterior pituitary gland from adult female rats to address whether the maturation of the hypothalamus-pituitary axis influences its effects and to corroborate whether these effects occur in physiological conditions such as during estrous cycle. E2 administration causes the same effect on sGC as seen in immature rats, and these effects are estrogen receptor dependent. These results suggest that E2 is the main effector of these changes. Since the sGC {alpha}-subunit increases while the sGC activity decreases, we studied if other less active isoforms of the sGC {alpha}-subunit are expressed. Here we show for the first time that sGC{alpha}2 and sGC{alpha}2 inhibitory ({alpha}2i) isoforms are expressed in this gland, but only sGC{alpha}2i mRNA increased after E2 acute treatment. Finally, to test whether E2 effects take place under a physiological condition, sGC subunit expression was monitored over estrous cycle. sGC{alpha}1, -β1, and -{alpha}2i fluctuate along estrous cycle, and these changes are directly related with E2 level fluctuations rather than to NO level variations. These findings show that E2 physiologically regulates sGC expression and highlight a novel mechanism by which E2 downregulates sGC activity in rat anterior pituitary gland.

estrogen; soluble guanylyl cyclase; inhibitory subunit


Address for reprint requests and other correspondence: B. H. Duvilanski, Departamento de Química Biológica, IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires (C1113AAD), Argentina (e-mail: neuroend{at}ffyb.uba.ar)






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