Age-related alterations in estrogen receptor dynamics are independent of cycling status in middle-aged C57BL/6J mice.
The objective of this study was to determine whether changes in estrogen receptor (ER) levels and dynamics that were previously observed in old acyclic mice were present in middle-aged mice and whether the cycling status of the mice influenced those changes. Young (3-6 months) regularly cycling and middle-aged (12-14 months) C57BL/6J mice that were either acyclic or still cycling regularly were injected with a dose of E2 (0.05 microgram/10 g body wt) sufficient to achieve maximal levels of nuclear ER (ERn) in all tissues examined: hypothalamus (HYPO), pituitary (PIT), and uterus (UT). The rise and fall of ERn and the replenishment of cytosolic ER (ERc) were measured 0, 1, 2, 4, 8, 12, and 24 h later. Cycling status did not affect ER binding profiles in middle-aged tissues. Therefore, data from cycling and acyclic subgroups were pooled for comparison with young mice. The increase in ERn following E2 injection, measured as the integrated area under the ERn profile, was reduced 33, 23, and 17%, respectively, in HYPO, PIT, and UT of middle-aged mice. In addition, the duration of elevated ERn was selectively reduced in middle-aged HYPO. ERc levels were reduced in middle-aged HYPO and UT, but replenishment rates were not altered. Reductions in total ER (ERn + ERc) were sufficient to account for the decline in ERn in middle-aged HYPO and UT, but factors in addition to ER loss appear to contribute to reduced ERn in middle-aged PIT. These results indicate that alterations in ER levels and dynamics occur prior to the transition to acyclicity, that these alterations are not secondary to hormonal or other changes associated with acyclicity, and that receptor loss appears to account for most of the age-related reduction in nuclear ER binding.
Bergman
M D
MD
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
Karelus
K
K
Felicio
L S
LS
Nelson
J F
JF
D000375:Aging; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004971:Estrus; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011960:Receptors, Estrogen / Q000097:blood*
D011960:Receptors, Estrogen