Estrogen and Glucocorticoid Metabolism

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Andersson, Therése,1978-Umeå universitet,Medicin,Tommy Olsson (författare)

Estrogen and Glucocorticoid Metabolism

BokEngelska2010

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Umeå :Institutionen för Folkhälsa och Klinisk Medicin,2010
62 s.
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:umu-33165
ISBN:9789172649736
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33165URI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:vet swepub-contenttype
Ämneskategori:dok swepub-publicationtype

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Umeå University medical dissertations,0346-6612 ;1345

Anmärkningar

Background: Cardiovascular disease (CVD) is the leading cause of death among women in Sweden. The risk of CVD increases rapidly after the menopause. A major contributing factor may be the redistribution of adipose tissue, from the peripheral to central depots, associated with menopause. This change in body composition is commonly attributed to declining estrogen levels but may also be affected by tissue-specific alterations in exposure to other steroid hormones, notably glucocorticoids – mainly cortisol in humans. Indeed, adipose tissue-specific overexpression of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) induces central obesity, insulin resistance and hypertension in mice. Interestingly, estrogen may regulate this enzyme. The aim of this thesis was to investigate putative links between estrogen and glucocorticoid activation by 11βHSD1. Materials and Methods: 11βHSD1 expression and/or activity in adipose tissue and liver, and adipose estrogen receptor α and β (ERα and ERβ) gene expression, were investigated in lean pre- and postmenopausal women and ovariectomized rodents with and without estrogen supplementation. In lean women measures of 11βHSD1 were correlated to risk markers for CVD. The association between adipose 11βHSD1 and ER mRNA expression was investigated in both lean women and rats and in an additional cohort of obese premenopausal women. In vitro experiments with adipocyte cell lines were used to explore possible pathways for estrogen regulation of 11βHSD1. Results: Subcutaneous adipose tissue transcript levels and hepatic activity of 11βHSD1 were higher in postmenopausal vs. premenopausal women. In rodents, estrogen treatment to ovariectomized rats decreased visceral adipose tissue 11βHSD1, resulting in a shift towards higher subcutaneous (vs. visceral) 11βHSD1 mRNA expression/activity. Increased adipose and hepatic 11βHSD1 were associated with increased blood pressure and a disadvantageous blood lipid profile in humans. We found significant positive associations between 11βHSD1 and ERβ transcript levels in adipose tissue. The in vitro experiments showed upregulation of 11βHSD1 mRNA expression and activity with estrogen or ERβ-agonist treatment at low (corresponding to physiological) concentrations. Conclusions: Our studies show for the first time increased local tissue glucocorticoid activation with menopause/age in women. This may contribute to an increased risk of CVD. Estrogen treatment in rodents induces a shift in 11βHSD1 activity towards the subcutaneous adipose tissue depots, which may direct fat accumulation to this metabolically “safer” depot. The in vitro studies suggest that low-dose estrogen treatment upregulates 11βHSD1 via ERβ. In summary, estrogen - glucocorticoid metabolism interactions may be key in the development of menopause-related metabolic dysfunction and in part mediate the beneficial effects of postmenopausal estrogen treatment on body fat distribution.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
11β-Hydroxysteroid Dehydrogenase Type 1
Estrogen
Cortisol
Adipose tissue
Liver
Menopause
Ovariectomy
Adipocyte
Estrogen Receptor β
Endocrinology
Endokrinologi
medicin
Medicine

Biuppslag (personer, institutioner, konferenser, titlar ...)

Olsson, Tommy,ProfessorUmeå universitet,Medicin (preses)
Mattsson, Cecilia,Med Dr, DocentUmeå universitet,Medicin (preses)
Söderström, Ingegerd,Med DrUmeå universitet,Medicin (preses)
Burén, Jonas,Fil DrUmeå universitet,Medicin (preses)
Holmäng, Agneta,ProfessorGöteborgs Universitet, Institutionen för Neurovetenskap och fysiologi (opponent)
Umeå universitetMedicin (creator_code:org_t)

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Av författaren/redakt...: Andersson, Theré ...; Olsson, Tommy, P ...; Mattsson, Cecili ...; Söderström, Inge ...; Burén, Jonas, Fi ...; Holmäng, Agneta, ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

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Av lärosätet: Umeå universitet

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