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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estradiol impairs hypothalamic molecular responses to hypoglycemia.
Hui Cheng1, Fumiko Isoda, Charles V Mobbs
1Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Brain Research
|May 19, 2009
Summary
Estradiol reduces the brain
Area of Science:
- Neuroendocrinology
- Metabolism
- Molecular Biology
Background:
- Estradiol is known to attenuate neuroendocrine responses to hypoglycemia in rats and humans.
- Hypoglycemia-induced neuroendocrine responses are mediated by hypothalamic neurons.
Purpose of the Study:
- To investigate if estradiol attenuates hypoglycemia-induced gene expression in the hypothalamus of female ovariectomized mice.
- To explore the hypothalamic mechanisms underlying estradiol's effects on counterregulatory responses to hypoglycemia.
Main Methods:
- Estradiol implantation in ovariectomized mice.
- Assessment of plasma hormone levels (insulin, glucagon).
- Measurement of gene expression (Glut1, IkappaB, POMC, c-fos, CPT1a, CPT1c, PDK4) in the hypothalamus and liver.
- Evaluation of body weight, visceral adiposity, and glucose tolerance.
Main Results:
- Estradiol treatment led to expected physiological changes including increased plasma estradiol, increased uterine weight, decreased body weight, decreased visceral adiposity, and enhanced glucose tolerance with decreased plasma insulin.
- Estradiol significantly attenuated hypoglycemia-induced gene expression of glucose transporter 1 (Glut1) and inhibitor of kappa beta signaling (IkappaB) in the hypothalamus, but not in the liver.
- Estradiol also attenuated hypoglycemia-induced plasma glucagon, pituitary proopiomelanocortin (POMC), and adrenal c-fos expression, indicating impaired counterregulatory responses.
- Hypothalamic expression of carnitine palmitoyltransferase (CPT1a and CPT1c) and pyruvate dehydrogenase kinase 4 (PDK4) was inhibited by estradiol, suggesting enhanced fatty acid accumulation and glycolysis.
Conclusions:
- Estradiol attenuates hypoglycemia-induced gene expression in the hypothalamus.
- These findings suggest that hypothalamic mechanisms mediate estradiol's attenuation of neuroendocrine responses to hypoglycemia.
- Estradiol's effects on hypothalamic gene expression may involve alterations in glucose and lipid metabolism.
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