17 β-estradiol (E2) modifies soluble guanylyl cyclase (sGC) expression in anterior pituitary gland from adult female rats under different physiological conditions

CABILLA, JP; DÍAZ, MC; MACHIAVELLI, LI; QUINTEROS, AF; DUVILANSKI, BH.

Toronto, Canada

Congreso; The Endocrine Society´s 89th annual meeting; 2007

Evidence from our laboratory indicates that E2 disrupts the inhibitory effect of NO onprolactin release, decreasing sGC activity and affecting the cGMP pathway in anteriorpituitary gland of adult ovariectomized (OVX) rats. Further, E2 acute treatment onimmature rats exerted opposite effects on the mRNA and protein expression of the twosGC subunits, increasing α1 and decreasing β1 levels (Cabilla JP et al., Endocrinology147:4311, 2006). To ascertain whether E2 affects sGC under physiological conditions,we investigated the changes on sGC expression in estrous cycle and OVX rats, and thein vivo effects of E2 administration in intact rats.During estrous cycle, α1 protein expression decreased on proestrus (relative units, P:0.65*) vs. levels in estrous (E: 0.97) and diestrus (D: 1.16, p<0.05) and β1 levelsincreased in P and E vs. D (P: 1.03**, E: 1.03**, D: 0.72, p<0.01 vs. D). Similar resultswere observed at the mRNA level of both subunits. In OVX rats, protein levels of sGCshowed no changes respect to control.Acute E2 treatment (40 μg E2/kg bw sc injection) in intact rats raised α1 levels at 4 h(21% of control) and 8 h (50%) and diminished β1 protein levels (4 h: 20% of control, 8h: 32%). Both subunits levels tended to return to control values after 12-16 h post-E2injection. The presence of one isoform with lower activity (α2) and the inhibitorysubunit α2i were detected for the first time in anterior pituitary. The augment in the αsubunit is not due to an increase in α2 or α2i expression. sGC activity was significantlyreduced at 8 h post-injection (50% vs. control) when the differences between subunits´expression were maximal. Chronic E2 administration for different times (byimplantation of silastic capsules containing E2) in intact rats resulted in a significantaugment in α1 protein levels (4 d: 60% of control, 7 d: 65%, 14 d: 54%), whereas β1levels were unaffected.These findings show that sGC expression fluctuates during estrous cycle, in parallelwith the changes in E2 levels. Acute and chronic E2 treatments raise α1 levels but notsGC activity. The lower production of cGMP reported under these conditions could bedue to a decrease in β1 expression or to the formation of α1/α1 inactive homodimers.Chronic removal of E2 seems not to affect sGC expression; therefore, the higherproduction of cGMP in OVX rats may be due to a higher activity of the enzyme.