Background matters: the effects of estrogen receptor α gene disruption on male sexual behavior are modified by background strain

Domı́nguez-Salazar, Emilio; Bateman, Heather L.; Rissman, Emilie F.

doi:10.1016/j.yhbeh.2004.05.006

Cited by 49 publications

(35 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the reason for the discrepancy is not clear, it may be partially due to differences in genetic backgrounds of the mice that were used in these two studies (75 versus 99% C57BL6), given that strain-dependent phenotypic variation has been recognized in the gene-targeted mice (54,55).…”

Section: Discussionmentioning

confidence: 99%

Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition

Zhang

Kernan

Collins

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Plasminogen (Plg) activator inhibitor-1 (PAI-1) is an important fibrosis-promoting molecule. Whether this effect can be attributed to PAI-1's activity as an inhibitor of plasmin generation is debated. This study was designed to investigate the role of Plg in renal fibrosis using in vivo and in vitro approaches. Plg-deficient (Plg؊/؊) and wild-type (Plg؉/؉) C57BL/6 mice were subjected to unilateral ureteral obstruction or sham surgery (n ‫؍‬ 8/group; sham, days 3, 7, 14, and 21). Plg deficiency was confirmed by the absence of Plg mRNA, protein, and plasmin activity. After 21 d of unilateral ureteral obstruction, total kidney collagen was significantly reduced by 35% in the Plg؊/؊ mice. Epithelial-to-mesenchymal transition (EMT), as typified by tubular loss of E-cadherin and acquisition of ␣-smooth muscle actin, was also significantly reduced in Plg؊/؊ mice, 76% and 50%, respectively. Attenuation of EMT and fibrosis severity in the Plg؊/؊ mice was associated with significantly lower levels of phosphorylated extracellular signal-regulated kinase (ERK) and active TGF-␤. In vitro, addition of plasmin (20 g/ml) to cultures of murine tubular epithelial cells initiated ERK phosphorylation within minutes, followed by phenotypic transition to fibroblast-specific protein-1؉, ␣-smooth muscle actin؉, fibronectin-producing fibroblast-like cells. Both plasmin-induced ERK activation and EMT were significantly blocked in vitro by the protease-activated receptor-1 (PAR-1) silencing RNA; by pepducin, a specific anti-PAR-1 signaling peptide; and by the ERK kinase inhibitor UO126. Plasmin-induced ERK phosphorylation was enhanced in PAR-1-overexpressing tubular cells. These findings support important profibrotic roles for plasmin that include PAR-1-dependent ERK signaling and EMT induction.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition

Zhang

Kernan

Collins

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Regarding the social recognition, female αERKO and βERKO mice have also been shown to differ in the extent of their attenuation of social memory . In addition, αERKO males displayed reduced aggressive behavior towards other males while βERKO males displayed enhanced inter-male aggressiveness relative to their WTs (Ogawa et al, 1998(Ogawa et al, , 2000Imwalle et al, 2002;Nomura et al, 2002;Rissman et al, 1999;Scordalakes and Rissman, 2003;Dominguez-Salazar et al, 2004). In this regard, it has been suggested that ERβ activation may exert an attenuating effect on male aggression induced by estrogen through ERα-mediated mechanisms (Nomura et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

Kavaliers

Devidze

Choleris

et al. 2008

Psychoneuroendocrinology

View full text Add to dashboard Cite

SummaryMale risk taking and decision making are affected by sex-related cues, with men making poorer and riskier decisions in the presence of females and, or their cues. In non-human species, female cues can also increase male risk taking, reducing their responses to predator threat. As estrogen receptors α and β (ERα and ERβ) are involved in the mediation of social and sexual responses, we investigated their roles in determining the effects of female-associated cues on male risk taking. We examined the effects of brief pre-exposure to the odors of either a novel or familiar estrous female on the avoidance of, and aversive responses to, predator threat (cat odor) in ERα and ERβ wild type (αERWT, βERWT) and gene-deleted (knockout, αERKO, βERKO) male mice. Exposure of αERWT and βERWT males to the odors of a novel, but not a familiar, estrous female mouse resulted in enhanced risk taking with the males displaying reduced avoidance of, and analgesic responses to, cat odor. In contrast, αERKO male mice failed to show any changes in risk taking, while βERKO males, although displaying greater risk taking, did not distinguish between novel and familiar females, displaying similarly reduced avoidance responses to cat odor after exposure to either a novel or familiar female odor. These findings indicate that the gene for ERα is associated with the sexual mechanisms (response to estrous female) and the genes for ERβ and ERα with the social (recognition of novel female) mechanisms underlying the effects of female cues on male risk taking. *Corresponding author. kavalier@uwo.ca (M. Kavaliers).

show abstract

“…First, we assessed their preferences for olfactory cues deriving from male and female C57BL/6J mice presented in soiled bedding. This is a sexually dimorphic behavior and these procedures have been published (Dominguez-Salazar et al, 2004). During the 10 min test, we recorded the time the subject spent investigating clean, male-soiled, or female-soiled bedding.…”

Section: Methodsmentioning

confidence: 99%

Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Gatewood¹,

Wills²,

Shetty³

et al. 2006

J. Neurosci.

220

227

View full text Add to dashboard Cite

Across human cultures and mammalian species, sex differences can be found in the expression of aggression and parental nurturing behaviors: males are typically more aggressive and less parental than females. These sex differences are primarily attributed to steroid hormone differences during development and/or adulthood, especially the higher levels of androgens experienced by males, which are caused ultimately by the presence of the testis-determining gene Sry on the Y chromosome. The potential for sex differences arising from the different complements of sex-linked genes in male and female cells has received little research attention. To directly test the hypothesis that social behaviors are influenced by differences in sex chromosome complement other than Sry, we used a transgenic mouse model in which gonadal sex and sex chromosome complement are uncoupled. We find that latency to exhibit aggression and one form of parental behavior, pup retrieval, can be influenced by both gonadal sex and sex chromosome complement. For both behaviors, females but not males with XX sex chromosomes differ from XY. We also measured vasopressin immunoreactivity in the lateral septum, which was higher in gonadal males than females, but also differed according to sex chromosome complement. These results imply that a gene(s) on the sex chromosomes (other than Sry) affects sex differences in brain and behavior. Identifying the specific X and/or Y genes involved will increase our understanding of normal and abnormal aggression and parental behavior, including behavioral abnormalities associated with mental illness.

show abstract

Background matters: the effects of estrogen receptor α gene disruption on male sexual behavior are modified by background strain

Cited by 49 publications

References 43 publications

Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition

Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition

Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Contact Info

Product

Resources

About