Estrogens sensitize anterior pituitary gland to apoptosis

Pisera, Daniel; Candolfi, Marianela; Navarra, S; Ferraris, Jimena; Zaldivar, V.; Jaita, Gabriela; Castro, María G.; Seilicovich, Adriana

doi:10.1152/ajpendo.00052.2004

Cited by 37 publications

(47 citation statements)

References 38 publications

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“…In advanced prostate cancer, sGC␣ 1 levels are highly correlated with proliferation (5). E 2 as a mitogenic factor, as well as a proapoptotic stimulus, drives changes in pituitary cell poblation (11,16,20). sGC␣ 1 levels and timing of pituitary cell proliferation seem to be correlated.…”

Section: Discussionmentioning

confidence: 96%

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

Cabilla¹,

Ronchetti²,

Nudler³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Cabilla JP, Ronchetti SA, Nudler SI, Miler EA, Quinteros FA, Duvilanski BH. Nitric oxide sensitive-guanylyl cyclase subunit expression changes during estrous cycle in anterior pituitary glands. Am J Physiol Endocrinol Metab 296: E731-E737, 2009. First published January 13, 2009 doi:10.1152/ajpendo.90795.2008.-17␤-Estradiol (E 2 ) exerts inhibitory actions on the nitric oxide pathway in rat adult pituitary glands. Previously, we reported that in vivo E 2 acute treatment had opposite effects on soluble guanylyl cyclase (sGC) subunits, increasing ␣ 1-and decreasing ␤1-subunit protein and mRNA expression and decreasing sGC activity in immature rats. Here we studied the E 2 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. E 2 administration causes the same effect on sGC as seen in immature rats, and these effects are estrogen receptor dependent. These results suggest that E 2 is the main effector of these changes. Since the sGC ␣-subunit increases while the sGC activity decreases, we studied if other less active isoforms of the sGC ␣-subunit are expressed. Here we show for the first time that sGC␣ 2 and sGC␣2 inhibitory (␣2i) isoforms are expressed in this gland, but only sGC␣ 2i mRNA increased after E2 acute treatment. Finally, to test whether E 2 effects take place under a physiological condition, sGC subunit expression was monitored over estrous cycle. sGC␣ 1, -␤1, and -␣ 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 THE MAIN ESTROGENIC HORMONE 17␤-estradiol (E 2 ) plays important regulatory roles in a broad variety of biological processes, acting mainly on reproductive tissues, bone, liver, pituitary, and brain (9, 25).Nitric oxide (NO) is a signaling molecule that freely diffuses across cellular membranes where it binds to its main intracellular receptor, soluble guanylyl cyclase (sGC). This enzyme catalyzes the formation of cGMP from GTP. Subsequently, targets of cGMP such as cGMP-dependent protein kinases, cyclic nucleotide phosphodiesterases, and cyclic nucleotidesensitive ion channels are activated to continue the signal transduction (15,18).sGC is an heterodimeric enzyme and is comprised of two subunits, ␣ and ␤, of which four types exist (␣ 1 , ␣ 2, ␤ 1 , and ␤ 2 ). Both ␣-isoforms form a functional enzyme with the ␤ 1 -subunit, although the ␣ 1 ␤ 1 is the most abundant and widely expressed heterodimer, showing the greater activity (12, 13). The ␣ 2 is expressed in a more restricted pattern: in human tissues, it is present mainly in spleen, placenta, brain, ...

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Section: Discussionmentioning

confidence: 96%

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

Cabilla¹,

Ronchetti²,

Nudler³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…In the present study, we show that DA induces apoptosis of anterior pituitary cells and lactotrophs only in the presence of E2, suggesting that estrogens exert a permissive action on the apoptosis induced by DA in these cells. In fact, we previously observed that estrogens increase the sensitivity of anterior pituitary cells to different apoptotic stimuli [19,20,21]. We also showed that lipopolysaccharide-induced apoptosis in the anterior pituitary gland is higher at proestrus than at other stages of the estrous cycle [21].…”

Section: Discussionmentioning

confidence: 98%

“…In fact, we previously observed that estrogens increase the sensitivity of anterior pituitary cells to different apoptotic stimuli [19,20,21]. We also showed that lipopolysaccharide-induced apoptosis in the anterior pituitary gland is higher at proestrus than at other stages of the estrous cycle [21]. Endogenous variations in circulating levels of estrogens may modulate apoptosis in the anterior pituitary gland by modifying its responsiveness to proapoptotic signals.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, in vitro studies from our laboratory showed that the apoptotic effects of TNF-α and FasL on anterior pituitary cells are estrogen-dependent and higher in cells from rats killed at proestrus than at diestrus [19, 20]. Also, in an in vivo model, the administration of estradiol to ovariectomized (OVX) rats induces apoptosis in the anterior pituitary gland and enables the proapoptotic action of endotoxemia [21]. …”

Section: Introductionmentioning

confidence: 99%

“…Considering that estrogens sensitize anterior pituitary cells to different proapoptotic stimuli [19, 20, 21], we investigated the effect of estradiol on the apoptotic actions of DA in anterior pituitary cells, especially lactotrophs. Taking into account that the mechanism by which DA induces apoptosis of anterior pituitary cells has not been clearly defined, we also studied the involvement of the D2 receptor and DAT in DA-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent

Radl

Zárate²,

Jaita³

et al. 2008

Neuroendocrinology

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Background/Aims: Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Methods: Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. Results: DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. Conclusion: These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis.

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The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 1: central nervous system, lung, and heart

Kawasaki

Chaudry

2012

J Anesth

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Although several clinical studies show a gender dimorphism of immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis, there are conflicting reports on the role of gender in outcomes. In contrast, results obtained from experimental studies clearly support the suggestion that gender plays a significant role in post-injury pathogenesis. Studies performed in a rodent model of trauma-hemorrhage have confirmed that alterations in immune and organ functions after trauma-hemorrhage are more markedly depressed in adult males and in ovariectomized and aged females; however, both are maintained in castrated males and in proestrus females. Moreover, the survival rate of proestrus females subjected to sepsis after trauma-hemorrhage is significantly higher than in age-matched males or ovariectomized females. In this respect, organ functions and immune responses are depressed in males with sepsis or trauma, whereas they are unchanged or are enhanced in females. This article reviews studies delineating the mechanism by which estrogen regulates cerebral nervous, lung, and heart systems in an experimental model of sepsis, trauma, or reperfusion injury.

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Estrogens sensitize anterior pituitary gland to apoptosis

Cited by 37 publications

References 38 publications

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

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

Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent

The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 1: central nervous system, lung, and heart

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