| Background Sex steroids appear to influence the metabolism of bone. Estrogens, in particular, are crucial for maintenance of bone mass in females as is evident from the rapid loss of trabecular bone and development of osteoporosis that occurs after ovariectomy or at menopause. Although the average age of women has increased from 50 to nearly 85 years, the average age at menopause still remained essentially constant at 50 years. Thus, women now spend nearly one third of their lives in an estrogen deficient state. This normal aging process in women is associated with some increasing health problems such as postmenopausal osteoporosis. The mechanism by which estrogen replacement therapy (ERT) maintain bone mass in women is still unclear. From the traditional point of view, estrogens play an important role in bone metabolism through indirect pass-ways of calcium-modulating hormones such as parathyroid hormone, Vitamin D, Calcitonin and so on. But in recent 20 years, the discovery of ERα and ERβ in osteoblast and osteoclast has madeus clear that bone is also the direct target organ of estrogens just like uterus and breast.ER is a kind of transcription factor and is a large molecule that mediates estrogens making the biological effect. ERa and ERβ belong to the steroid/thyroid hormone super family of nuclear receptors, member of which have a common structural architecture. ERa and ERβ are the products of two genes located on different chromosomes but both proteins are encoded by eight exons. Their biological activities are similar, but the distributions in tissues and cells are very distinctive. Binding to an ER ligand triggers conformational change in the receptor and this leads, via a number of events, to the change in the rate of transcription of estrogen-regulated genes. The order in which ehese events occur in the overall process, are not completely understood. It includes receptor dimerization, receptor-DN A interaction, recruitment of and interaction with co-activators and other transcription factors, and formation of a pre initiation complex. Estrogens interact with ERa and ERβ to activate or repress gene transcription. A recent study has demonstrated that most genes regulated by ERβ are distinct from those regulated by ERa in response to E2. These results indicate that estrogens exert tissue-specific effects by regulating unique sets of targets genes through ERα and ERβ. We speculate ERα and ERβ have different functions in bone metabolism and their expression vary with the growth status of bone.In bone tissue, both ERα and ERβ express abundantly in trabecular bone, and little has been detected in cortical bone. The degree of bone loss in trabecular bone is much greater than it is in cortical bone after menopause. It's still a matter of controversy about which ER subtype expresses predominantly in trabecular bone. In addition, how estrogens modulate the expression of ERα and ERβ and affect the trabecular bone metabolism is not very clear. Previous studies involving ERa and ERβ mostly focused on uterus and mamma, but few on bone tissue. Besides, mostreports about ERs in bone have paid more attention to ERa than ERp and also more to mRNA than to protein level, lacking of comparison between them.ERT has shown to play an important beneficial role in the health and well being of postmenopausal women. Several estrogen preparations are available, among which conjugated equine estrogens (CEE) and estradiol valerate (EV) are most widely used. But whether the bone protections of CEE and EV are similarly is still not proven, especially from the viewpoint of the mechanisms of ERa and ERβ modulation in bone metabolism. So we need to understand the function of estrogens in bone growth clearly. Besides to study the special relationship between ERa and ERβ mediating estrogens action, we still have to compare the effects of estrogen preparations with different components on bone protection.Objective We made rat models of osteoporosis through ovariectomy (OVX), and two different estrogens preparations were given res...
|
PDF Full Text Request