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re$valuate the assumption that the changes outlined in Table II are independent of the sex or hormonal status of the patient. The possibility exists
that some of the changes ascribed to chronologic
aging are actually reflections of decreasing levels of
circulating androgens.
TABLEI
Skin ChangesDueto Photoaging
* Winkles and furrows
* Solarlentigines(liverspots)
e Telangiectasias
* Mottledpigmentation
* Senilepurpura
* Actinickeratoses
@Basalcellandsquamouscellcarclnamas
* A subsetof melanomas
INFLUENCEOF ANDROGENS
Whole Skin
TABLEII
Skin ChangesAssociatedwith ChronologicAging
* Dryness
* Increasedfragilfty
* Decreasedepidermalthickness(atrophyI,t
* Decreaseindermalthickness(a$ophy),t
* Fragmentation
of elasticfibers(saggingit
* Decreasedsebumproductton
8 Decreasednumberandfunction of apocrine glands8
* Decreased growth of body hairs
nRuenced by circulatinglevels of estrogens.
lay be Influenced by crrculating levels of androgens.
robably Influenced by circulating levels of estrogens.
robably Influenced by levels of circulahng androgens.
TABLEIll
Localizationof SorReductaseActivity and Androgen
Receptorsin the Skin*,t
5&eductese
Activity
Hair
Androgen
Receptors
Epidermal keratlnocfles
Dermalfibroblasts
Hairfollicles
External root sheath
Matrix epithelrum
+%
+%
+
+I1
+I
t
t
t
t
Sebaceousglands
Apocmeglands
In contrast to their effect on the dermis, the influence of circulating estrogens on the structure
and function of the epidermis is rather confusing
given the opposite effects-atrophy
(thinning) as
well as thickening-that
have been reported in
postmenopausal women receiving estrogen replacement therapy [ll]. In summary, it is necessary to
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January
16,1995
cw.
The possible importance of the papilla cells is
underscored by transplantation
studies in animals
in which the origin of the papilla cells (not the origin
of the hair epithelium) determined the type of hair
produced [ZO]. It has been possible to isolate and
culture dermal papilla cells, and experiments have
shown that the papilla cells isolated from beard hair
have higher 5Lu-reductase activity than those isolated from occipital scalp hair or reticular dermal
fibroblasts [21]. This suggests that dermal papilla
cells may play a role in androgen-dependent
hair
growth.
Fibroblasts
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drogens for treatment of osteoporosis also experienced an increase in total skin collagen content [36].
Keratinocytes
Epidermal
turnover time, as assessed by tritiated thymidine uptake following intradermal
injection, has been shown to decrease by approximately
50% from age 20 to 70 years, and replacement time
for the stratum corneum is nearly doubled in the
elderly [37]. A relationship between androgens and
epidermal function has been known since the 1950s.
In castrated male mice, a decrease in epidermal
mitotic activity was observed when compared with
control animals, and subcutaneous injections of testosterone propionate restored the mitotic activity
to normal [381. Additional studies in castrated male
rats demonstrated an increase in the rate of epiderma1 cell proliferation
following the administration
of testosterone but no associated increase in the
thickness of the epidermis [39].
More recent studies have pointed to the presence
of androgen receptors as well as 5a-reductase activity in the keratinocytes of the epidermis. Immunohistochemical
studies using both polyclonal and
monodonal antibodies directed against the androgen receptor have demonstrated specific staining in
the nuclei of the cells of the epidermis in both genital (male) and nongenital (male and female) skin
[17-191. In one study, the proportion of skin specimens with positive staining was higher in men
(62%) than in women (23%) [19]. Cloning of 5~
reductase cDNAs from adult keratinocyte
cDNA
libraries has shown a predominance of the type I
form of the enzyme 1261. In addition to 5a-reductase
activity, other enzymatic activities found in epiderma1 keratinocytes include 3P-hydroxysteroid
oxidoreductase and 17phydroxysteroid
oxidoreductase,
suggesting that the epidermis represents a site of
synthesis of biologically potent androgens in human
skin [40].
The fact that no investigations into the effects of
testosterone alone on skin aging in women have
been reported points to the obvious need for studies
in this area.
ACKNOWLEDGMENT
I wish to thank Steven R. Kohn, M.D., for his
helpful suggestions.
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