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

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.

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Nitric Oxide-Sensitive Guanylyl Cyclase α1- and β1-Subunits Are Differentially Regulated by Classical and Non-Classical Estrogen Pathways in Anterior Pituitary Gland

10.1210/endo-meetings.2011.part3.p17.p3-22 ◽

2011 ◽

pp. P3-22-P3-22

Author(s):

Jimena Paula Cabilla ◽

Sonia Alejandra Ronchetti ◽

Silvana Iris Nudler ◽

Fernanda Alnilan Quinteros ◽

Beatriz Haydee Duvilanski

Keyword(s):

Nitric Oxide ◽

Pituitary Gland ◽

Guanylyl Cyclase ◽

Anterior Pituitary ◽

Anterior Pituitary Gland

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Nitric oxide sensitive-guanylyl cyclase subunit expression changes during estrous cycle in anterior pituitary glands

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90795.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. E731-E737 ◽

Cited By ~ 13

Author(s):

Jimena P. Cabilla ◽

Sonia A. Ronchetti ◽

Silvana I. Nudler ◽

Eliana A. Miler ◽

Fernanda A. Quinteros ◽

...

Keyword(s):

Nitric Oxide ◽

Pituitary Gland ◽

Estrous Cycle ◽

Guanylyl Cyclase ◽

Anterior Pituitary ◽

Acute Treatment ◽

Α Subunit ◽

Immature Rats ◽

Subunit Expression ◽

Pituitary Glands

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 α1- 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 α-subunit increases while the sGC activity decreases, we studied if other less active isoforms of the sGC α-subunit are expressed. Here we show for the first time that sGCα2 and sGCα2 inhibitory (α2i) isoforms are expressed in this gland, but only sGCα2i 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. sGCα1, -β1, and -α2i 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.

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Nitric Oxide-Sensitive Guanylyl Cyclase Is Differentially Regulated by Nuclear and Non-Nuclear Estrogen Pathways in Anterior Pituitary Gland

PLoS ONE ◽

10.1371/journal.pone.0029402 ◽

2011 ◽

Vol 6 (12) ◽

pp. e29402 ◽

Cited By ~ 8

Author(s):

Jimena P. Cabilla ◽

Silvana I. Nudler ◽

Sonia A. Ronchetti ◽

Fernanda A. Quinteros ◽

Mercedes Lasaga ◽

...

Keyword(s):

Nitric Oxide ◽

Pituitary Gland ◽

Guanylyl Cyclase ◽

Anterior Pituitary ◽

Anterior Pituitary Gland

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Estrogens sensitize anterior pituitary gland to apoptosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00052.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. E767-E771 ◽

Cited By ~ 22

Author(s):

D. Pisera ◽

M. Candolfi ◽

S. Navarra ◽

J. Ferraris ◽

V. Zaldivar ◽

...

Keyword(s):

Pituitary Gland ◽

Estrous Cycle ◽

Anterior Pituitary ◽

Anterior Pituitary Gland ◽

Female Rats ◽

Cell Renewal ◽

Apoptotic Response ◽

Ovx Rats ◽

17Β Estradiol ◽

Induced Apoptosis

Tissue homeostasis results from a balance between cell proliferation and cell death by apoptosis. Estradiol affects proliferation as well as apoptosis in hormone-dependent tissues. In the present study, we investigated the apoptotic response of the anterior pituitary gland to lipopolysaccharide (LPS) in cycling female rats, and the influence of estradiol in this response in ovariectomized (OVX) rats. The OVX rats were chronically estrogenized with implanted Silastic capsules containing 1 mg of 17β-estradiol (E2). Cycling or OVX and E2-treated rats were injected with LPS (250 μg/rat ip). Apoptosis was determined by the terminal deoxynucleotidyl-mediated dUTP nick-end labeling (TUNEL) method in sections of the anterior pituitary gland and spleen. Chronic estrogenization induced apoptosis in the anterior pituitary gland. Acute endotoxemia triggered apoptosis of cells in the anterior pituitary gland of E2-treated rats but not of OVX rats. No differences were observed in the apoptotic response to LPS in spleen between OVX and E2-treated rats. The apoptotic response of the anterior pituitary to LPS was variable along the estrous cycle, being higher at proestrus than at estrus or diestrus I. Approximately 75% of the apoptotic cells were identified as lactotropes by immunofluorescence. In conclusion, our results indicate that estradiol induces apoptosis and enables the proapoptotic action of LPS in the anterior pituitary gland. Also, our study suggests that estrogens may be involved in anterior pituitary cell renewal during the estrous cycle, sensitizing lactotropes to proapoptotic stimuli.

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