Sex-based differences in gene transmission and gene expression

Ostrer, Harry

doi:10.1177/096120339900800507

Cited by 26 publications

(9 citation statements)

References 49 publications

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“…Sex effects, or sexual dimorphism, refer to differential susceptibility to a disease in both males and females (Ostrer 1999;Seeman 1997). Such differences have traditionally been linked with genetic risk factors on sex chromosomes.…”

Section: Sexual Dimorphismmentioning

confidence: 99%

Understanding Bipolar Disorder: The Epigenetic Perspective

Khare

Pal

Petronis

2010

Behavioral Neurobiology of Bipolar Disorder and Its Treatment

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Bipolar disease (BPD) is a complex major psychiatric disorder that affects between 1% and 2% of the population and exhibits ?85% heritability. This has made BPD an appealing target for genetic studies yet, despite numerous attempts, the genetic basis of this disease remains elusive. Recently, it has come to light that epigenetic factors may also influence the development of BPD. These factors act via stable but reversible modifications of DNA and chromatin structure. In this chapter, we revisit the epidemiological, clinical, and molecular findings in BPD and reanalyze them from the perspective of inherited and acquired epigenetic misregulation. Epigenetic research has great potential to enhance our understanding of the molecular basis of BPD.

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Section: Sexual Dimorphismmentioning

confidence: 99%

Understanding Bipolar Disorder: The Epigenetic Perspective

Khare

Pal

Petronis

2010

Behavioral Neurobiology of Bipolar Disorder and Its Treatment

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“…The percentage of women participating in clinical research has declined since the year 2000 in spite of legislative directives for their inclusion the cells are derived. These influences include the possibility that a single exposure to a sex steroid hormone may influence cellular metabolism through multiple passages of the cells in culture (Antoniucci et al 2001;Avner and Heard 2001;Csaba et al 1990;Hager et al 2008;Isensee and Ruiz Noppinger 2007;Isensee et al 2008;Ivanova and Beyer 2003;McEwen 2001;Ober et al 2008;Ostrer 1999;Pierce et al 2009;Rzewuska-Lech et al 2005;van Nas et al 2010;Wang et al 2006;Waxman et al 1985;Yang et al 2006;Yao et al 2010). However, the sex and hormonal or reproductive status of the cell/tissue donor or experimental animals is not consistently reported (Beery and Zucker 2011;Taylor et al 2011;Zucker and Beery 2010).…”

Section: Cultured Cells and Progenitor (Pluripotent Stem Cells)mentioning

confidence: 99%

Considerations of Sex and Gender Differences in Preclinical and Clinical Trials

Raz

Miller

2012

Handbook of Experimental Pharmacology

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Women continue to be underrepresented in clinical trials, particularly in Phases I and II of experimental drug studies in spite of legislative guidelines in the USA, Canada, the European Union, Australia, and Japan requiring the inclusion of women in clinical trials. As such, women remain a vulnerable population subject to the adverse effects of pharmacological therapies. Thus, women experience higher rates of adverse drug reactions than do men and for women of reproductive age or who may be pregnant, therapeutic options may be limited. This chapter provides a brief history of inclusion of sex and gender as variables in clinical trials, summarizes governmental legislation for consideration of sex and gender in clinical trials and provides specific examples of drugs which have been withdrawn from the market because of side effects in women. Additional information related to sex and gender in preclinical testing, trial design, challenges to recruitment of women for clinical trials and statistical methods for analysis of data also is considered.

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“…2 Future experimental studies should address the specificity of SERMs on activation of NOS isoforms related to estrogen receptor affinity and efficacy in leukocytes from both male and female animals. [35][36][37] In summary, the article by García-Durán et al 10 provides an additional mechanism by which estrogen may affect physiological functions, in particular, function of neutrophils. However, caution is needed in extrapolating findings from studies performed on isolated cells to understanding how a particular action of estrogen may be involved in gender difference in the expression of human disease.…”

Section: ϫ10mentioning

confidence: 99%

Gender, Estrogen, and NOS

Miller

1999

Circulation Research

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Evidence from observational studies as well as prospective randomized trials indicates that the incidence of coronary artery disease is less in premenopausal women compared with age-matched men and in postmenopausal women who are using estrogen replacement therapy. 1,2 The mechanisms by which estrogen reduces development of cardiovascular disease are multifactorial and, in addition to alterations in lipid metabolism, include actions on all components of the vascular wall (endothelial, smooth muscle, and adventitial cells), neurons, and blood elements (platelets and leukocytes). Changes in production of nitric oxide (NO) have been implicated as one of the cellular biochemical-related pathways regulated by estrogen that may contribute to gender and hormonal differences in the progression of cardiovascular disease. [3][4][5][6][7][8][9] NO is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). NOS consists of three isoforms: type I, neuronal; type II, inducible; and type III, endothelial/ constitutive. In this issue of Circulation Research, García-Durán et al 10 add to the accumulating body of evidence suggesting that estrogen directly modulates expression of NOS, in particular the neuronal isoform (type I) in neutrophils. With use of Western blot analysis of protein isolated from neutrophils, levels of neuronal NOS were greater in neutrophils from premenopausal women during the ovulatory phase of the estrus cycle when estrogen is high compared with the follicular phase when circulating levels of estrogen fall. In addition, expression of neuronal NOS increased in neutrophils of postmenopausal women who were using transdermal estrogen replacement (50 mg/d) for 4 months. The range of circulating estrogen over which these changes in neuronal NOS occurred was physiological, between 5ϫ10 Ϫ10and 2ϫ10Ϫ9 mol/L. These observations suggest that changes in circulating levels of oxidized products of nitric oxide in blood of women during different stages of the estrus cycle as well as with estrogen replacement therapy may be derived from cells other than the those of the endothelium. [11][12][13][14] García-Durán et al 10 examined the gender specificity of estrogen on expressional control of neuronal NOS using neutrophils from male subjects. In these cells, there was both a time and dose dependency of induction of neuronal NOS by estrogen. This induction was receptor mediated and showed biphasic stimulation with increases in NOS from 10 Ϫ10 to 10 Ϫ8 mol/L of estrogen and inhibition at higher concentrations. These concentration ranges are similar to those shown to stimulate neuronal NOS isolated from rabbit cerebellum. 15 The observation that estrogen can modulate NOS isoform in male cells is consistent with observations of increases in reactive hyperemia, a vascular response mediated by endothelium-derived NOS, in male to female transsexuals. 16 As provocative as these results might be, much remains to be learned regarding effects of sex steroid hormones on leukocyte function and how these effects relate to g...

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Sex-based differences in gene transmission and gene expression

Cited by 26 publications

References 49 publications

Understanding Bipolar Disorder: The Epigenetic Perspective

Understanding Bipolar Disorder: The Epigenetic Perspective

Considerations of Sex and Gender Differences in Preclinical and Clinical Trials

Gender, Estrogen, and NOS

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