Effects of gender and stress on the regulation of steroid receptor coactivator-1 expression in the rat brain and pituitary

Bousios, S; Karandrea, Despoina; Kittas, C; Kitraki, Efthimia

doi:10.1016/s0960-0760(01)00123-6

Cited by 55 publications

(33 citation statements)

References 18 publications

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“…The present data demonstrating a heterogeneous expression of SRC-1 in the brain as well as a significant sex difference in expression in the preoptic area-hypothalamus, along with a few recent papers and abstracts suggest that the latter scenario is the more probable [100, 101, 102]. The Japanese quail, a species that displays dramatic seasonal changes in steroid production and action, should constitute an outstanding model to address this question.…”

Section: Discussionmentioning

confidence: 65%

Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

et al. 2002

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The steroid receptor coactivator SRC-1 modulates ligand-dependent transactivation of several nuclear receptors, including the receptors for sex steroid hormones. Reducing the expression of SRC-1 by injection of specific antisense oligonucleotides markedly inhibits the effects of estrogens of the sexual differentiation of brain and behavior in rats and inhibits the activation of female sexual behavior in adult female rats. SRC-1 thus appears to be involved in both the development and activation of sexual behavior. In the Japanese quail brain, we amplified by RT-PCR a 3,411-bp fragment extending from the HLH domain to the activating domain-2 of the protein. The quail SRC-1 is closely related to the mammalian (m) SRC-1 and contains a high proportion of GC nucleotides (62.5%). Its amino acid sequence presents 70% identity with mammalian SRC-1 and contains the three conserved LXXLL boxes involved in the interaction with nuclear receptors. In both males and females, RT-PCR demonstrates a similarly high level of expression in the telencephalon, diencephalon, optic lobes, brain stem, spinal cord, pituitary, liver, kidney, adrenal gland, heart, lung, gonads and gonoducts. Males express significantly higher levels of SRC-1 in the preoptic area-hypothalamus than females. In both sexes, lower levels of expression are observed in the cerebellum and muscles. In situhybridization utilizing a mixture of four digoxigenin-labeled oligonucleotides confirms at the cellular level the widespread distribution of SRC-1 mRNA in the brain and a particularly dense expression in steroid-sensitive areas that play a key role in the control of male sexual behavior. These data confirm the presence and describe for the first time the SRC-1 distribution in the brain of an avian species. They confirm its broad, nearly ubiquitous, distribution in the entire body including the brain as could be expected for a coactivator that regulates to the action of many nuclear receptors. However this distribution is heterogeneous in the brain and sexually differentiated in at least some areas. The very dense expression of SRC-1 in limbic and mesencephalic nuclei that are associated with the control of male sexual behavior is consistent with the notion that this coactivator plays a significant role in the activation of this behavior.

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Section: Discussionmentioning

confidence: 65%

Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

et al. 2002

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“…Significant gender-and sitespecific differences in the expression of SRC-1 in the brain and pituitary gland under basal conditions and following acute stress have previously been noted in rats by Northern blot analysis [22]. Finally, an additional possibility for the differential effects of loss of SRC-1 on trabecular bone in female vs. male mice could be related to compensation for loss of SRC-1 by SRC-2 in male, but not in female mice.…”

Section: Discussionmentioning

confidence: 80%

The skeletal response to estrogen is impaired in female but not in male steroid receptor coactivator (SRC)-1 knock out mice

Mödder

Sanyal

et al. 2008

Bone

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Estrogen (E) is critical for the maintenance of bone mass in both female and male mice and steroid receptor coactivator (SRC)-1 has been shown to be important for mediating E effects on bone, at least in female mice. In the present study, we defined the skeletal phenotype of male SRC-1 knock out (KO) mice and compared it with their female littermates. Further, to determine the role of SRC-1 in mediating effects of E on bone in male mice, we examined the skeletal effects of gonadectomy (gnx) with or without E replacement in male mice and placed these findings in the context of our previous studies in female SRC-1 KO mice.Analysis of a large group of male (WT, n=67; SRC-1 KO, n=56) and female (WT, n=66; SRC-1 KO, n=70) mice showed a significant decrease in trabecular volumetric bone mineral density (vBMD) in SRC-1 KO mice compared to their WT littermates in both genders (male SRC-1 KO, 275 ± 3 vs WT, 295 ± 3 mg/cm 3 , P<0.001; female SRC-1 KO, 210 ± 2 vs WT, 221 ± 2 mg/cm 3 , P<0.001). Following gnx and E replacement (10 μg/kg/d), we previously demonstrated that SRC-1 KO female mice have a defect in E action in trabecular, but not in cortical bone. In contrast, we now demonstrate that the same dose of E administered to gnx'd male SRC-1 KO mice was sufficient to prevent trabecular bone loss in these mice. For example, in WT female mice, gnx followed by E replacement maintained spine BMD (1.2 ± 3.4% vs baseline) as compared to gnx without E replacement (−12.7 ± 2.6%, P<0.001 vs sham); this effect of E was absent in SRC-1 KO female mice. By contrast, the identical dose of E was equally effective in maintaining spine BMD in E-treated gnx'd male WT (−5.2 ± 5.1% vs baseline) and male SRC-1 KO (−5.4 ± 5.3%) mice, respectively, as compared to gnx'd mice without E treatment (WT, −17.6 ± 2.5%, P=0.02; SRC-1 KO, −28.6 ± 2.6%, P<0.001 vs sham). E treatment was effective in suppressing cancellous bone turnover in both gnx'd WT and SRC-1 KO male mice as determined by significant reductions in osteoblast and osteoclast numbers; however, in female mice, E treatment only suppressed bone turnover in WT but not in SRC-1 KO mice.Collectively, these findings demonstrate that loss of SRC-1 results in trabecular osteopenia in male and female mice, but in contrast to female mice, this is not due to any detectable resistance to E action in trabecular bone in male SRC-1 KO mice.

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“…The findings described in this paper indicate that coactivators such as SRC-1 represent another class of proteins that are important for regulating steroid action in adulthood on brain and behavior. We already know that its expression is not constitutive but rather is regulated by a variety of factors, including sex steroid hormones and stress (Bousios et al, 2001;Charlier et al, 2004). It remains to be seen to what extent natural variation in this protein can explain intra-specific variation in the effects of sex steroids on sexual behavior.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

Charlier¹,

Ball²,

Balthazart³

2005

J. Neurosci.

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Effects of gender and stress on the regulation of steroid receptor coactivator-1 expression in the rat brain and pituitary

Cited by 55 publications

References 18 publications

Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

The skeletal response to estrogen is impaired in female but not in male steroid receptor coactivator (SRC)-1 knock out mice

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

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