scholarly journals Gonadal- and Sex-Chromosome-Dependent Sex Differences in the Circadian System

Endocrinology ◽  
2013 ◽  
Vol 154 (4) ◽  
pp. 1501-1512 ◽  
Author(s):  
Dika A. Kuljis ◽  
Dawn H. Loh ◽  
Danny Truong ◽  
Andrew M. Vosko ◽  
Margaret L. Ong ◽  
...  
Keyword(s):  
Sex Differences ◽  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Sex Chromosome ◽  
Gonadal Hormones ◽  
Circadian System ◽  
Receptor Expression ◽  
Male Mice ◽  
Activity Duration ◽  
Wheel Running Activity

Abstract Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system.

scholarly journals Sex Differences in Ischemic Stroke Sensitivity Are Influenced by Gonadal Hormones, Not by Sex Chromosome Complement

2014 ◽  
Vol 35 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Bharti Manwani ◽  
Kathryn Bentivegna ◽  
Sharon E Benashski ◽  
Venugopal Reddy Venna ◽  
Yan Xu ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Sex Hormones ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Serum Testosterone ◽  
Gonadal Hormones ◽  
Epidemiologic Studies ◽  
Artery Occlusion ◽  
Male Mice

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

scholarly journals Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen receptors in mice

2008 ◽  
Vol 53 (3) ◽  
pp. 422-430 ◽  
Author(s):  
Eiko Iwahana ◽  
Ilia Karatsoreos ◽  
Shigenobu Shibata ◽  
Rae Silver
Keyword(s):  
Sex Differences ◽  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Androgen Receptors

Gonadal hormone effects on entrained and free-running circadian activity rhythms in the developing diurnal rodent Octodon degus

2007 ◽  
Vol 292 (1) ◽  
pp. R586-R597 ◽  
Author(s):  
Daniel L. Hummer ◽  
Tammy J. Jechura ◽  
Megan M. Mahoney ◽  
Theresa M. Lee
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Sexual Differentiation ◽  
Gonadal Hormones ◽  
Circadian System ◽  
System Structure ◽  
Octodon Degus ◽  
Activity Rhythms ◽  
Free Running ◽  
The Impact

The slowly maturing, long-lived rodent Octodon degus (degu) provides a unique opportunity to examine the development of the circadian system during adolescence. These studies characterize entrained and free-running activity rhythms in gonadally intact and prepubertally gonadectomized male and female degus across the first year of life to clarify the impact of sex and gonadal hormones on the circadian system during adolescence. Gonadally intact degus exhibited a delay in the phase angle of activity onset (Ψon) during puberty, which reversed as animals became reproductively competent. Gonadectomy before puberty prevented this phase delay. However, the effect of gonadal hormones during puberty on Ψon does not result from changes in the period of the underlying circadian pacemaker. A sex difference in Ψon and free-running period (τ) emerged several months after puberty; these developmental changes are not likely to be related, since the sex difference in Ψon emerged before the sex difference in τ. Changes in the levels of circulating hormones cannot explain the emergence of these sex differences, since there is a rather lengthy delay between the age at which degus reach sexual maturity and the age at which Ψon and τ become sexually dimorphic. However, postnatal exposure to gonadal hormones is required for sexual differentiation of Ψon and τ, since these sex differences were absent in prepubertally gonadectomized degus. These data suggest that gonadal hormones modulate the circadian system during adolescent development and provide a new model for postpubertal sexual differentiation of a central nervous system structure.

scholarly journals Neural Growth Hormone Implicated in Body Weight Sex Differences

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3826-3835 ◽  
Author(s):  
Paul J. Bonthuis ◽  
Emilie F. Rissman
Keyword(s):  
Body Weight ◽  
Sex Differences ◽  
Food Intake ◽  
X Chromosome ◽  
Sex Chromosome ◽  
Gonadal Hormones ◽  
Sexually Dimorphic ◽  
X Chromosomes ◽  
Body Weights ◽  
Neural Growth

As for many human diseases, the incidence of obesity and its associated health risks are sexually dimorphic: worldwide the rate of obesity is higher in women. Sex differences in metabolism, appetite, body composition, and fat deposition are contributing biological factors. Gonadal hormones regulate the development of many sexually dimorphic traits in humans and animals, and, in addition, studies in mice indicate a role for direct genetic effects of sex chromosome dosage on body weight, deposition of fat, and circadian timing of feeding behavior. Specifically, mice of either sex with 2 X chromosomes, typical of normal females, have heavier body weights, gain more weight, and eat more food during the light portion of the day than mice of either sex with a single X chromosome. Here we test the effects of X chromosome dosage on body weight and report that gonadal females with 2 X chromosomes express higher levels of GH gene (Gh) mRNA in the preoptic area (POA) of the hypothalamus than females with 1 X chromosome and males. Furthermore, Gh expression in the POA of the hypothalamus of mice with 2 X chromosomes correlated with body weight; GH is known to have orexigenic properties. Acute infusion of GH into the POA increased immediate food intake in normal (XY) males. We propose that X inactivation–escaping genes modulate Gh expression and food intake, and this is part of the mechanism by which individuals with 2 X chromosomes are heavier than individuals with a single X chromosome.

scholarly journals Sexual Differentiation and Substance Use: A Mini-Review

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Samuel J Harp ◽  
Mariangela Martini ◽  
Wendy J Lynch ◽  
Emilie F Rissman
Keyword(s):  
Sex Differences ◽  
Sexual Behaviors ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Brain Structures ◽  
Gonadal Hormones ◽  
Future Research ◽  
Sexually Dimorphic ◽  
Self Administration ◽  
Four Core Genotype

Abstract The organizational/activational hypothesis suggests that gonadal steroid hormones like testosterone (T) and estradiol (E2) are important at 2 different times during the lifespan when they perform 2 different functions. First steroids “organize” brain structures early in life and during puberty, and in adults these same hormones “activate” sexually dimorphic behaviors. This hypothesis has been tested and proven valid for a large number of behaviors (learning, memory, social, and sexual behaviors). Sex differences in drug addiction are well established both for humans and animal models. Previous research in this field has focused primarily on cocaine self-administration by rats. Traditionally, observed sex differences have been explained by the sex-specific concentrations of gonadal hormones present at the time of the drug-related behavior. Studies with gonadectomized rodents establishes an activational role for E2 that facilitates vulnerability in females, and when E2 is combined with progesterone, addiction is attenuated. Literature on organizational actions of steroids is sparse but predicts that T, after it is aromatized to E2, changes aspects of the neural reward system. Here we summarize these data and propose that sex chromosome complement also plays a role in determining sex-specific drug-taking behavior. Future research is needed to disentangle the effects of hormones and sex chromosome complement, and we propose the four core genotype mouse model as an effective tool for answering these questions.

scholarly journals Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases

2017 ◽  
Vol 37 (5) ◽  
pp. 746-756 ◽  
Author(s):  
Arthur P. Arnold ◽  
Lisa A. Cassis ◽  
Mansoureh Eghbali ◽  
Karen Reue ◽  
Kathryn Sandberg
Keyword(s):  
Sex Differences ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Sex Chromosome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Gonadal Hormones ◽  
Protective Mechanisms ◽  
Harmful Effects ◽  
Specific Control

This review summarizes recent evidence concerning hormonal and sex chromosome effects in obesity, atherosclerosis, aneurysms, ischemia/reperfusion injury, and hypertension. Cardiovascular diseases occur and progress differently in the 2 sexes, because biological factors differing between the sexes have sex-specific protective and harmful effects. By comparing the 2 sexes directly, and breaking down sex into its component parts, one can discover sex-biasing protective mechanisms that might be targeted in the clinic. Gonadal hormones, especially estrogens and androgens, have long been found to account for some sex differences in cardiovascular diseases, and molecular mechanisms mediating these effects have recently been elucidated. More recently, the inherent sexual inequalities in effects of sex chromosome genes have also been implicated as contributors in animal models of cardiovascular diseases, especially a deleterious effect of the second X chromosome found in females but not in males. Hormonal and sex chromosome mechanisms interact in the sex-specific control of certain diseases, sometimes by opposing the action of the other.

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