|
|
| Search |
|---|
| Vibrance Newsletter | ||
|---|---|---|
|
|
||
| Androgen Receptor Expression in Women and its Relationship to Sexual Function |
|
|
|
| Written by Jennifer Berman, MD | |||||||||||||
Page 10 of 11 Androgens have an important function in regulating bone matrix production and organization. ARs are up-regulated by androgens in bone and also by exposure to glucocorticoids, estrogen and vitamin D. Androgen exposure enhances osteoblast differentiation and the synthesis of extracellular matrix proteins. Androgens also stimulate bone mineralization and influence bone cells’ function through the effect on local and systemic factors that control the bone cells’ microenvironment. The synthesis of transforming growth factor (TGF) β, a potent osteoblast mitogen, as well as insulin-like growth factor (IGF) II and fibroblast growth factor are all influenced by DHT and T. Androgens also decrease osteoclast genesis by inhibiting the production of interleukin-6 (IL-6) in the stromal cells of the bone marrow, resulting in diminished maturation and development of osteoclast precursors and osteoclasts.69 The reduction of IL-6 has been demonstrated for T, DHT, A and DHEA. Furthermore, T and DHT also regulate osteoclast activity, thereby reducing bone turnover by inhibiting both parathyroid hormone and IL-1-stimulated prostaglandin E2 production.69N. Anabolic effects of androgen There are clear associations among muscle mass, muscle strength and bone density in that muscle exerts a greater load on bone than does weight-dependent gravity. Mechanical loading when combined with estrogen, results in a greater osteogenic response than either separately. This is probably the result of estrogen’s antiresorptive effect and of the stimulation of bone formation with exercise.69 Approximately 4% of muscle mass is lost during the first 3 years after menopause, which is associated with a significant decline in muscle strength.70 In men, muscle strength is preserved until age 60 years and reaches levels found in menopausal women at about 75 years of age, which may explain the greater tendency for falls in older women.71 Androgens have direct anabolic effects on skeletal muscle as T increases lean body mass and decreases fat mass in a dose- and concentration-dependent fashion. In addition, the administration of androgens is associated with the up-regulation of androgen receptors and resultant increased responsiveness of skeletal muscle.72 The action of T on muscle involves multiple mechanisms including its effects on inducing protein synthesis, recruiting satellite cells, and modulating the commitment of pluripotent mesenchymal cells to myogenic lineage.52 T supplementation has been shown to increase muscle mass in older men and HIV-infected men with low testosterone, chronic debilitative illnesses and healthy, but hypogonadal men, with the anabolic effects on muscle mass dependent on dose and plasma concentration.52, 73 The T-induced muscle fiber hypertrophy was also associated with a dose-dependent increase in myonuclear number inside the muscle fiber.72 In addition to the stimulation of muscle protein synthesis, T also affected satellite cells, which are quiescent precursors of skeletal muscle. In response to T, satellite cells proliferated and then fused subsequently with the muscle fibers resulting in an increase in myonuclear number and muscle fiber hypertrophy. The observed increase in the number of satellite cells were seen in men who were treated with supraphysiological doses of T.52, 72 Administration of T and DHT have been shown to be associated with increasing muscle mass and decreasing fat mass. Bhasin et al74 demonstrated that testosterone supplementation in older men, young hypogonadal men, and middle-aged men with visceral obesity resulted in a decrease in fat mass which was proportional to the administered testosterone doses. Hence supraphysiologic doses of T may produce a strong anabolic effect and T may also influence additional steps in the myogenic and adipogenic pathways, muscle-protein synthesis, and satellite cell replication.52 O. Androgen effects on the cardiovascular system In recent years, there has been a dramatic increase in research into androgen effects on the cardiovascular system. Whereas previously androgens were considered harmful (and estrogens protective) for the cardiovascular system, current evidence suggests that androgens have beneficial or neutral cardiovascular effects and that they exert different effects at early (plaque formation) and late (rupture, thrombosis, vasospasm) stages of atherosclerosis.75 An increasing number of studies demonstrate protective effects of androgens on cardiovascular function. However these findings derive almost entirely from male patients, and hold undetermined relevance for women’s cardiovascular health. Nonetheless, limited human data does suggest that testosterone exposure does not shorten life span in either gender, and oral estrogen treatment increases the risk of cardiovascular death in men as it does in women. Patterns of age-specific cardiovascular death rates provide little support for the gender gap being due to estrogen protection. Rather, androgen exposure in early life (perinatal androgen imprinting) may predispose males to earlier onset of atherosclerosis, but the subsequent tempo of atherosclerotic progression is similar in men and women.75 Future research on women’s cardiovascular health will promote a better understanding of AR coregulators, nongenomic androgen effects, tissue-specific metabolic activation of androgens, and androgen sensitivity. P. Conclusion The importance of androgens in women is now being recognized as an essential component in maintaining sexual health and overall well-being. Extensive research has documented the physiologic role of androgen receptors throughout the body as well as its involvement in cancers of the reproductive tract. However additional basic science and clinical trials are needed to further assess the role of androgens in premenopausal women as well as during the natural decline that occurs with aging and menopause, and the abrupt losses that occur with surgical menopause. In addition to quality of life and sexual outcomes, the impact of androgens on the pelvic floor and genital tract, muscle, bone, cognitive and cardiovascular function require improved characterization with future studies. |
|||||||||||||
| Last Updated ( Monday, 26 March 2007 ) | |||||||||||||
