A single dose of enterolactone activates estrogen signaling and regulates expression of circadian clock genes in mice.

Enterolactone (EL) is an enterolignan produced by gut microbiota from dietary plant lignans. Epidemiological and experimental studies suggest that EL and plant lignans may reduce the risk of breast and prostate cancer as well as cardiovascular disease. These effects are thought to at least in part involve modulation of estrogen receptor activity. Surprisingly little is known about the in vivo estrogenicity of EL. In the present study, we investigated the target tissues of EL, the genes affected by EL treatment, and the response kinetics. Following a single dose of EL, luciferase was significantly induced in reproductive and nonreproductive tissues of male and female 3xERE-luciferase mice, indicating estrogen-like activity. Microarray analysis revealed that EL regulated the expression of only 1% of 17β-estradiol target genes in the uterus. The majority of these genes were traditional estrogen target genes, but also members of the circadian signaling pathway were affected. Kinetic analyses showed that EL undergoes rapid phase II metabolism and is efficiently excreted. In vivo imaging demonstrated that the estrogen response followed similar, fast kinetics. We conclude that EL activates estrogen signaling in both male and female mice and that the transient responses may be due to the fast metabolism of the compound. Lastly, EL may represent a link among diet, gut microbiota, and circadian signaling.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
4-Butyrolactone
analogs & derivatives
blood
pharmacology
Animals
CLOCK Proteins
genetics
metabolism
Circadian Clocks
drug effects
genetics
Estradiol
pharmacology
Estrogens
metabolism
Female
Gene Expression Regulation
drug effects
Lignans
blood
pharmacology
Liver
metabolism
Luciferases
metabolism
Male
Mice
Mice
Inbred C57BL
Orchiectomy
Ovariectomy
Phytoestrogens
pharmacology
Protein Array Analysis
Random Allocation
Signal Transduction
drug effects
Uterus
metabolism

Nurmi, Tarja (författare)
Salminen, Anu (författare)
Damdimopoulos, Anastasios EKarolinska Institutet (författare)
Kotka, Maria (författare)
van der Saag, Paul (författare)
Strauss, Leena (författare)
Poutanen, MattiGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xpouma (författare)
Pongratz, IngemarKarolinska Institutet (författare)
Mäkelä, Sari (författare)
Karolinska InstitutetCentre for Bone and Arthritis Research (creator_code:org_t)

Av författaren/redakt...: Damdimopoulou, P ...; Nurmi, Tarja; Salminen, Anu; Damdimopoulos, A ...; Kotka, Maria; van der Saag, Pa ...; visa fler...; Strauss, Leena; Poutanen, Matti; Pongratz, Ingema ...; Mäkelä, Sari; visa färre...

Om ämnet

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

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