HORMONE REPLACEMENT THERAPY INCREASES TYPE I COLLAGEN IN DERMAL FIBROBLASTS BY STIMULATING TRANSFORMING GROWTH FACTOR-BETA
Neena Philips* and Jan Devaney
Natural Sciences, Mathematics and Computer Science Department, Georgian Court College, 900 Lakewood Ave, Lakewood, NJ 08701.
A consequence of aging is the reduced secretion of most hormones and the altered responsiveness of tissues to hormones. Decreases in the levels of estrogen and progesterone are associated with many changes in the body, one of which is skin aging that manifests as fine/coarse wrinkling and impaired wound healing. The alteration in skin are in addition due to exposure to ultraviolet radiation and the collective changes in skin are referred to as "photoaging". Photoaging is largely due to the alterations in the extracellular matrix proteins (synthesized largely by dermal fibroblasts), reduction in collagen and increases in the expressions of elastin and collagenase. Associated with aging is the reduced activation of TGF-b. TGF-b is a major modulator of the extracellular matrix. Photoaging and replicative senescence is associated with extracellular matrix degradation and reduced levels of active TGF-b. Synthetic estrogen and progesterone have been used as hormone replacement therapy (HRT) in postmenopausal women to compensate for the decrease in these hormone levels. HRT has been reported to improve skin quality and wound healing. Estrogen has been reported to induce TGF-b. However, there are no reports on the effects of estrogen, progesterone and the combination (HRT) on the alterations of the skin extracellular matrix or on TGF-b activation/expression.
The purpose of this study was to determine whether hormone replacement therapy (HRT) can improve skin aging by increasing expressions of type I collagen and active TGF-b. To this end, the effects of estrogen, progesterone, and the combination of estrogen and progesterone on human dermal fibroblasts, with regards to cell proliferation and expressions of type I collagen, TGF-b and latency associated peptide (LAP) were examined. Initially, fibroblasts were untreated or exposed to estrogen (1, 10, 100, or 1000nM), progesterone (0.1, 1, 10, or 100 mM), or a combination of estrogen and progesterone concentrations for 24 or 48 hours. Relative to untreated fibroblasts, all doses of estrogen, progesterone and the combination inhibited cell proliferation similarly after 24 and 48 hours of treatment. The hormones did not alter type I collagen in 24 hours. However, after 48 hours of treatment, estrogen and progesterone, independently caused significant dose responsive increases in collagen secretion and the combinations of estrogen and progesterone enhanced collagen secretions further, in dose dependent manner. Fibroblasts exposed to 100nM estrogen, 1mM progesterone or a combination of these hormones for 48 hours demonstrated increased release of TGF-b, but not LAP. It can be inferred that estrogen and progesterone can independently increase type I collagen expression and can act synergistically in combination to enhance collagen expression further in dermal fibroblasts. HRT may be mediating the increase in collagen expression, and thereby skin quality, by increasing the release of active TGF-b.
The delineation of effects of HRT in the skin will permit better intervention in the management of photoaging and wound healing, particularly in the elderly. An understanding of the mechanisms of action of HRT can form a basis for the replacement of HRT with treatments with antioxidants or/and stimulators of TGF-b.
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