Bone loss in ovariectomized rats: dominant role for estrogen but apparently not for FSH.
Estrogen deficiency as the sole factor underlying post-menopausal osteoporosis was challenged, in light of reports that both follicular stimulation hormone (FSH) receptor and FSHβ knockout mice were resistant to bone loss, suggesting a detrimental role for FSH. We assessed whether lowering FSH levels by gonadotropin realizing (GnRH) analog decapeptyl in ovariectomized female rats (OVX) affects bone. Wistar-derived 25 days old OVX female rats were injected for 10 weeks with estradiol-17β (E(2)), with GnRH analog (decapeptyl) or with both. FSH and luteinizing hormone (LH) serum levels were markedly increased in OVX rats, with smaller growth plates with disrupted architecture; heavy infiltration of bone marrow with numerous adipocytes and reduced thickness of cortical bone. In OVX rats treated with E(2), FSH, and LH levels were intermediate, the tibia was similar to that of intact rats, but there was reduced thickness of cortical bone. In decapeptyl treated OVX rats, FSH and LH levels were suppressed, the organization of growth plate and the trabecular bone were disrupted, and there were fewer proliferative and chondroblastic cells and a large adipocytes population in bone marrow, but an increased trabecular bone volume (TBV). In the E(2) + decapeptyl treatment, FSH and LH levels were suppressed, with partially restored growth plate architecture and improved TBV. In conclusion, E(2) deficiency is the dominant factor impairing bone loss in OVX and concomitant changes in FSH/LH levels achieved by decapeptyl have some modulating, though complex role in this setting. The role of high FSH levels in post-menopausal bone loss requires further investigation using combined sub-optimal doses of the different hormones.
Institute of Endocrinology, Metabolism and Hypertension, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel.
V
V
Rouach
S
S
Katzburg
Y
Y
Koch
N
N
Stern
D
D
Somjen
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology*; D010052:Ovariectomy; D051381:Rats; D017329:Triptorelin Pamoate / Q000494:pharmacology
D004967:Estrogens; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone