Effects of estrogen receptor alpha- and beta-selective substances in the metaphysis of the tibia and on serum parameters of bone and fat tissue metabolism of ovariectomized rats.

摘要

The functions of estrogen receptors (ER) alpha and beta (ER-alpha and beta) in bone and fat tissue are not precisely described. Therefore we studied the effects of a specific ERalpha and ERbeta agonist in bone and fat of ovariectomized (ovx) rats and compared them with the effects of estradiol (E2). Animals were s.c. injected for 4-weeks with 3 doses of the ERalpha agonist 16alpha-LE2 or the ERbeta agonist 8beta-VE2 or with E2. The intermediate doses were antagonized by an additional daily treatment with ICI (1.53mg). Bone and fat parameters were evaluated by quantitative computer tomography (qCT). Estrogen regulated hormones were also measured. Uterine weights were stimulated; serum LH and leptin levels suppressed E2 and the ERalpha agonist. Density of the cancellous metaphyseal structures of the tibia was reduced in the controls which was prevented by E2 and the ERalpha agonist. Endosteal surface, endosteal, periosteal circumferences and fat depots were largest in the controls and the ERbeta treated animals and lowest in the E2 and the 16alpha-LE2 injected ovx rats. Osteocalcin and the CrossLaps were highest in the ovx controls and reduced by E2 and the ERalpha agonist. Serum osteocalcin was stimulated by the ERbeta agonist. The strain strength index (SSI) in relation to the bodyweight - an indicator of bone elasticity - was lowest in controls and increased dose dependently in the E2 and in the ERalpha treated animals. Most effects in the uterus, serum and bone were antagonized by ICI. Most effects in the bone and fat were exerted by mechanisms involving the ERalpha but the ERbeta agonist appears to stimulate osteoblasts.