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.
Andersson
Niklas
N
Center for Bone Research at the Sahlgrenska Academy, Division of Endocrinology, Department of Internal Medicine, Göteborg University, Gröna stråket 8 SE-413 45 Göteborg, Sweden. niklas.andersson@medic.gu.se
Islander
Ulrika
U
Egecioglu
Emil
E
Löf
Elin
E
Swanson
Charlotte
C
Movérare-Skrtic
Sofia
S
Sjögren
Klara
K
Lindberg
Marie K
MK
Carlsten
Hans
H
Ohlsson
Claes
C
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D000077267:Fulvestrant; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism* / Q000503:physiopathology; D010052:Ovariectomy; D013977:Tibia / Q000187:drug effects / Q000503:physiopathology; D014057:Tomography, X-Ray Computed
D004343:Drug Implants; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D004958:Estradiol