Investigation of central versus peripheral effects of estradiol in ovariectomized mice

• It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.

Nyckelord

Animals

Bone Density

Bone and Bones/*drug effects

Brain/*drug effects

Dose-Response Relationship

Drug

Drug Implants

Estradiol/*administration & dosage/analogs & derivatives/pharmacology

Estrogen Antagonists/pharmacology

Female

Femur/drug effects/physiopathology

Humans

Mice

Mice

Inbred C57BL

Middle Aged

Models

Animal

Osteoporosis

Postmenopausal/*metabolism/physiopathology

Ovariectomy

Tibia/drug effects/physiopathology

Tomography

X-Ray Computed

Femur/drug effects/physiopathology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)