Estrogen modulates Bcl-2 family protein expression in the sexually dimorphic nucleus of the preoptic area of postnatal rats

Tsukahara, Shinji; Hojo, Rieko; Kuroda, Yoshiko; Fujimaki, Hidekazu

doi:10.1016/j.neulet.2007.12.006

Cited by 40 publications

(31 citation statements)

References 25 publications

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“…This idea is consistent with evidence that developmental exposure to E 2 upregulates bax (proapoptotic molecule) and downregulates bcl2 (anti-apoptotic molecule) to defeminize the male AVPV (Tsukahara et al, 2008;Forger, 2009). Consequently, the male AVPV is significantly smaller than that of the female (Forger et al, 2004) and cannot support the cyclic surge pattern of LH release necessary for ovulation (Petersen et al, 2012).…”

Section: Introductionsupporting

confidence: 88%

“…Of those targets, Cugbp2 (also known as Bruno-like protein 3, Celf-2, Napor and ELAV-type RNAbinding protein 3) emerged as an especially interesting candidate because it encodes a proapoptotic protein (Choi et al, 1999;Mukhopadhyay et al, 2003b;Ramalingam et al, 2008). In addition, it is upregulated in the AVPV of males and E 2 -treated females wherein apoptosis is also elevated (Arai et al, 1996;Tsukahara et al, 2008). Furthermore, previous work shows that Cugbp2 regulates RNA stabilization, translation and splicing of genes previously associated with glutamate signaling and sexual differentiation of the POA.…”

Section: Discussionmentioning

confidence: 99%

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Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol

et al. 2015

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Section: Introductionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol

et al. 2015

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“…Bax is a pro-apoptotic member of the Bcl-2 family, and in Bax-deficient mice, there is no significant sex difference in number of neurons in BNSTp in adult mice [3] or in number of apoptotic cells in BNSTp in postnatal mice [41]. Postnatal EB treatment in female rats can reduce the degree of sex difference in the size of SDN-POA by decreasing the number of apoptotic cells [43], and this decrease is due to the up-regulation of anti-apoptotic Bcl-2 expression and the down-regulation of pro-apoptotic Bax expression in the SDN-POA of these females [44]. Therefore, estrogen may modulate the expression of the Bcl-2 family members in the BNSTp of postnatal mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of Aromatase or Estrogen Receptor Gene Deletion on Masculinization of the Principal Nucleus of the Bed Nucleus of the Stria Terminalis of Mice

et al. 2011

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The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is a sexually dimorphic nucleus, and the male BNSTp is larger and has more neurons than the female BNSTp. To assess the roles of neuroestrogen synthesized from testicular androgen by brain aromatase in masculinization of the BNSTp, we performed morphometrical analyses of the adult BNSTp in aromatase knockout (ArKO), estrogen receptor-α knockout (αERKO), and estrogen receptor-β knockout (βERKO) mice and their respective wild-type littermates. In wild-type littermates, the BNSTp of males had a larger volume and greater numbers of neuronal and glial cells than did that of females. The volume and neuron number of the BNSTp in ArKO and αERKO males and glial cell number of the BNSTp in αERKO males were significantly smaller than those of wild-type male littermates, and they were not significantly different from those in female mice with either gene knockout. In contrast, there was no significant morphological difference in the BNSTp between βERKO and wild-type mice. Next, we examined the BNSTp of ArKO males subcutaneously injected with estradiol benzoate (EB) on postnatal days 1, 2, and 3 (1.5 µg/day). EB-treated ArKO males had a significantly greater number of BNSTp neurons than did oil-treated ArKO males. The number of BNSTp neurons in EB-treated ArKO males was comparable to that in wild-type males. These findings suggested that masculinization of the BNSTp in mice involves the actions of neuroestrogen that was synthesized by aromatase and that this estrogen mostly binds to ERα during the postnatal period.

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“…This pathway is activated by severe injury such as ischemia or neurotoxic agents (Roof and Hall, 2000). In another model that does not involve insult, estrogen decreases apoptosis in the sexually dimorphic nucleus of the preoptic hypothalamus in postnatal rats by increasing Bcl-2 and decreasing Bax (Tsukahara et al, 2008) although downstream effectors have not been elucidated. In this study, we show that HT may increase DRN neuronal resilience in the absence of injury through actions on JNK1 and downstream by actions on AIF, a pivotal protein in the caspase -independent pathway.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective actions of ovarian hormones without insult in the raphe region of rhesus macaques

2008

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Using a nonhuman primate model of surgical menopause, our laboratory has shown that ovarian hormone treatment (HT) improves serotonin neural function in the dorsal raphe nucleus (DRN). We further hypothesize that HT may increase serotonin neuronal resilience. Recent data from microarray analysis indicated that HT regulates gene expression in pathways that lead to apoptosis. In this study, we questioned whether HT alters protein expression in caspase-dependent and independent pathways. Ovariectomized monkeys received Silastic implants containing placebo (empty), estrogen (E) or E+ progesterone (P). A small block of the midbrain containing the DRN was dissected and subjected to subcellular fractionation, yielding cytosolic, nuclear and mitochondrial fractions( (n=4/ group). The pro-apoptotic protein, JNK1 and its phosphorylation were decreased by E+P treatment in the cytosolic fraction. Downstream of JNK are proteins in the caspase-dependent and independent pathways. First, in the caspase-dependent pathway, cytoplasmic and mitochondrial fractions were immunoblotted for Bcl-2 family members, cytochrome c, Apaf1 and XIAP. However, the expression of these proteins did not differ among treatments. Pro-caspase 3 was decreased by E+P, but there was no evidence of active caspase in any group. Then, we examined the involvement of a protein in the caspase-independent pathway, called apoptosis-inducing factor (AIF). AIF mRNA (n=3/group) and AIF mitochondrial protein tended to decrease with hormone treatment. However, AIF protein in the nuclear fractions in E+P treated monkeys was significantly reduced. This indicates that HT is reducing the translocation of AIF from mitochondria to nucleus, thus inhibiting AIF-mediated apoptosis. AIF was immunocytochemically localized to large serotonin-like neurons of the dorsal raphe. This data suggests that in the absence of global trauma or ischemia, HT may act through the caspase-independent pathway to promote neuroprotection in the serotonin system.

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Estrogen modulates Bcl-2 family protein expression in the sexually dimorphic nucleus of the preoptic area of postnatal rats

Cited by 40 publications

References 25 publications

Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol

Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol

Effects of Aromatase or Estrogen Receptor Gene Deletion on Masculinization of the Principal Nucleus of the Bed Nucleus of the Stria Terminalis of Mice

Neuroprotective actions of ovarian hormones without insult in the raphe region of rhesus macaques

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