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

Abstract The functions of estrogen receptors (ER) alpha and beta (ER-α and β) in bone and fat tissue are not precisely described. Therefore we studied the effects of a specific ERα and ERβ 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 ERα agonist 16α-LE2 or the ERβ agonist 8β-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 ERα agonist. Density of the cancellous metaphyseal structures of the tibia was reduced in the controls which was prevented by E2 and the ERα agonist. Endosteal surface, endosteal, periosteal circumferences and fat depots were largest in the controls and the ERβ treated animals and lowest in the E2 and the 16α-LE2 injected ovx rats. Osteocalcin and the CrossLaps were highest in the ovx controls and reduced by E2 and the ERα agonist. Serum osteocalcin was stimulated by the ERβ 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 ERα 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 ERα but the ERβ agonist appears to stimulate osteoblasts.