Age dependency of estrogen responsiveness in the uterus and adipose tissue of aromatase-knockout (ArKO) mice.
Aging is often associated with weight gain caused by metabolic changes including an increase of body fat. In this study we assessed the impact of age on estrogen responsiveness in the uterus and adipose tissue (AT) in aromatase-knockout (ArKO) mice. ArKO mice at the age of three or twelve months respectively were treated s.c. with vehicle, E(2) (10 μg/kg BW/d) or genistein (15 mg/kg BW/d) for three days. In the ArKO mouse model we were able to demonstrate that estrogen treatment resulted in an age specific response pattern both on a physiological and molecular level. Assessment of basal gene expression levels revealed significant age dependent differences only for elevated Esr1 levels in the uterus and leptin levels in infrarenal fat as well as lower levels of Pparg in the gonadal fat tissue. Investigating age dependency of estrogen responsiveness we were able to show that the E(2) and genistein resulted in age related pattern of regulation of expression of Esr1 and Lep in infrarenal and gonadal AT as well as the uterine expression of Pgr, Ltf and Pparg. In conclusion, evidence is provided that aging has an impact on the effectiveness of estrogen regulated processes in uterus and AT of ArKO mice. It remains to be elucidated whether or not this is associated with weight gain caused by an increase in body fat mass.
Institute for Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
Manuela I
MI
Bader
Christine
C
Reitmayer
Claudia
C
Arndt
Jannette
J
Wober
Georg
G
Kretzschmar
Oliver
O
Zierau
Günter
G
Vollmer
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001141:Aromatase / Q000235:genetics*; D001786:Blood Glucose; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D019833:Genistein / Q000494:pharmacology; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D011897:Random Allocation; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D004967:Estrogens; D020738:Leptin; D011987:Receptors, Steroid; D019833:Genistein; D001141:Aromatase