Browsing by Subject "Hormones"

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    Effects of dietary fat and omega-3 fatty acids on eicosanoids, endogenous sex hormones and the insulin-like growth factor pathway
    (2010-06) Orr, Lindsay Rae
    This dissertation details a clinical trial that investigated the effects of three controlled, 8-week duration test diets: a high fat diet (HF; 40% of energy from fat), a low fat diet (LF; 20% of energy from fat), and a low fat diet high in omega-3 (n-3) fatty acids (LFn3; 23% energy from fat including 3% of energy from n-3 fatty acids) on breast cancer risk markers including plasma and urinary sex hormones, urinary eicosanoids, and insulin-like growth factor (IGF) pathway endpoints in postmenopausal women. Chapter 1 contains a review of the literature providing context for the clinical trial. Chapter 2 describes the effects of the three test diets on plasma phospholipid fatty acids (PLFA), urinary eicosanoids, and plasma sex hormones. The LFn3 diet significantly increased plasma n-3 PLFA and the HF diet significantly increased estradiol and urinary eicosanoids. These results indicate that high fat diet increases breast cancer risk markers, but are inconclusive with respect to n-3 fatty acids. Chapter 3 describes the effect of the three test diets on urinary sex hormones and metabolites. Urinary excretion of estrone was significantly greater after the LF and LFn3 compared to the HF; however in the context of all the urinary hormones and metabolites measured, this indicates that no clinically significant alterations were observed following the test diets. Chapter 4 details the effects of the test diets on IGF pathway endpoints. LFn3 increased IGF-I and IGF binding protein-3 (IGFBP-3) and the LF increased IGFBP-3. These results indicate that low fat diet may reduce free IGF-I while the addition of n-3 fatty acids to the low fat diet may increase free IGF-I concentrations. The impact on breast cancer risk mediated by the increase in IGF-I with the LFn3 is unknown, but an increase in circulating IGF-I may have an impact on reducing the effects of aging. In conclusion, the test diets had pronounced effects on PLFA but modest effects on plasma and urinary sex hormones. The LFn3 unexpectedly increased IGF-I concentrations, which may demonstrate a role of n-3 in preventing the effects of aging.
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    mGluR5 Structural Plasticity in the Nucleus Accumbens: Characterization, Mechanism, and Sex Differences
    (2017-10) Gross, Kellie S
    The group I metabotropic glutamate receptors, mGluR1 and mGluR5, are important modulators of neuronal signaling and plasticity. One specific way that group I mGluRs appear to influence excitatory neurotransmission is through the remodeling of neuronal structure by inducing changes to dendritic spines. However, group I mGluR spine remodeling has only been studied in an extremely limited number of regions and cell types, leaving the contribution of this mechanism to plasticity in many systems unknown. Group I mGluRs, especially mGluR5, have been associated with the synaptic plasticity in the reward circuitry of the brain that is believed to underlie addiction. Structural changes in this circuitry, particularly in the nucleus accumbens (NAc) are strongly correlated with the development and maintenance of addiction. Yet a potential relationship between mGluR5 signaling and spine plasticity in the NAc has not been directly studied. Here, the effects of mGluR5 signaling on spine plasticity in medium spiny neurons of the NAc are characterized, with particular attention on the sex differences and hormonal regulation of these effects. Activation of mGluR5 signaling is found to decrease spine density in the NAc with sex differences in subregion specificity. Additionally, primary gonadal hormones are found to trigger mGluR5 signaling to produce structural modulation in the NAc, with previous evidence implicating mGluR5 in estradiol-induced spine changes in this region in females, and research here finding a similar, novel role for androgen signaling in males. The mechanisms of mGluR5-mediated spine plasticity are also explored. Endocannabinoid signaling was found to be required for mGluR5-induced spine decreases in the male NAc, and spine changes were found to be correlated with a change in NAc F-actin content. Collectively, these results indicate that mGluR5 signaling results in structural plasticity in a region that is critical to reward in a sex-dependent manner, suggesting that the activity of this receptor might contribute differently to both natural and pathological motivated behavior in males and females.