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Effect of estradiol on hyaluronic acid in the skin of aging mice
EFFECT OF ESTRADIOL ON HTALURONIC ACID IN THE SKIN OF AGING MICE Harry Sobel Aging Research Laboratory, Veterans Administration Hospital, Californla 91343 and Department of Biochemistry,
Sepulveda,
Colorado State
University, Fort Collins, Colorado 80521 and Ronald A. Cohen Aging Research Laboratory, Veterans Administration Hospital, Sepulveda, California 91343
Received:
March 20, 1970 ABSTRACT
Estradiol dipropionate administered to male Swiss mice at a daily dose of I0 ~g for 5 days increased the hyaluronic acid content of the skin. This effect was observed in groups of mice ranging in age from i00 - 750 days and was, thus, not affected by the age of the animals.
A marked decrease occurs in hyaluronic acid (HA) and chondroitin sulfate (CS) contents of the skin of male mice with age (i). in the females is considerably less.
The change
Estradiol dipropionate at a dose
of 5 ~g daily for 5 days produced a ~arked increase in HA in the skins of young male mice (2).
It therefore seemed desirable
~o test the
effect of estradiol on male mice of different ages.
MATERIALS AND METHODS Male Swiss mice were obtained from c o ~ e r c i a l suppliers, and, after 3 weeks quarantine, were aged at this hospital. They were fed commercial rat pellets. T h e conditions of housing were less than desired. Mortality was 40% at one year of age and virtually 1007. by two years. Mice of 5 age catagories were selected for this experiment. A dose of i0 ~g of estradlol dipropionate in 0.I ml of sesame oil was injected daily, subcutaneously, for 5 days. Controls received oil alone. On the 6th day, the pelts were taken and the isolation and measurement of HA and CS were carried out as previously described (3). The results were expressed as hyaluronlc acid hexosamine and chondroitin sulfate hexosamine.
ST ER O I D S
16:1
RESULTS
~e
findings are shown in Table I.
HA wlth age.
Th'e data show a 28Z decrease in
Estradiol induced approximately a twofold increase in each
of the 5 groups ranging from the youngest to the oldest. decrease in CS with age.
Estradlol
There was 30Z
d i d not produce a s i g n i f i c a n t
increase
i n CS.
TABLE i Hyaluronic Acid Hexosamine (HAH) and Chondroltin Sulfate Hexosamlne (CSH) in the Total Skin of Male Swiss Mice of Various Age Following Estradiol Administration.
AGE (Days) i00=250
GROUP
NO, 15 17
WEIGHT START (g) 41.9 ± i.I* 41.7 ± 0.8
WEIGHT FINISH (~) 43.2 ± I.i 44.1 ± 0.7
}IAH (ug) 448 ± 55 1045 ± 76**
CSH (ug) 263 ± 19 314 ± 25
Control Treated
250-350
Control Treated
17 18
45.2 ± I.I 45.7 ± 1.0
45.8 ± 1.0 46.7 ± 1.0
447 ± 23 905 ± 66**
244 ± 15 276 ± 16
350-500
Control Treated
15 18
43.2 ± 1.7 44.4 ± I.i
44.0 ± 1.0 46.7 ± I.i
357 ± 28 769 ± 32**
224 ± 17 242 ± II
500-650
Control Treated
Ii 13
43.4 ± 1.6 46.4 ± 2.5
43.5 ± 1.7 47.5 ± 2.3
346 ± 24 618 ± 45**
223 ± 12 229 ± 18
Control 9 46.8 ± 3.3 47.2 ± 3.1 323 ± 28*** Treated 9 45.5 ± 1.4 45.3 ± 1.6 672 ± 56** Standard error. P < .001 compared wlth controls of same age. P < .02 compared with 250-350 day old group. P • ,01 compared with 2~0-350 day old group~
650-750 w-, ,_,_,_,
183 ± 14;~;4 204 ± 15
DISCUSSION It was earlier observed that a dose of 5 ~g estradiol dipropionate administered
to young mice (22 - 23 gms) resulted in a marked increase
in HA in the skin, a smaller dose and larger dose were less effective. The present daily dose of i0 ~g was used to accommodate weight of the older animals.
the greater
Since the "physiologic dose" of estradiol
for the mouse is usually taken to be less than .01 ~g, the present dose
July 1970
S T ER O I D S
is definitely "unphysiological".
Nevertheless,
3 the data show that t h e
oldest mice are markedly susceptible to the effect of estradiol on HA in the skin, although this effect is somewhat less than in the youngest group.
The increase in HA was about double while CS did not exhibit a
statistically significant effect. preparation,
Whatever the site of action of the
the findings suggest that age does not effect its delivery
to the fibroblasts nor the response of the latter to it.
ACKNOWLEDGMENT S This project was supported in part by Part I funds of the Veterans Administration, by NASA Grant NGR-05-O07-113, NSF Grant GB-662~ and by Navy Contract NOO014-67-A-OII-0008.
REFERENCES i.
Sobel, H., Hewlett, M. J., and Hrubant, H. E., J. GERONTOL., In press.
2.
Sobel, H., Lee, K. D., and Hewlett, M. J., BIOCHIM. BIOPHYS. ACTA, i01, 225 (1965).
3.
Sobel, H., Hewlett, M. J., Hoshek, S., and Sacker, I. Mo, AMXR, J. PHYSIOL., 212, 773 (1967).
Sepulveda,
Colorado State
University, Fort Collins, Colorado 80521 and Ronald A. Cohen Aging Research Laboratory, Veterans Administration Hospital, Sepulveda, California 91343
Received:
March 20, 1970 ABSTRACT
Estradiol dipropionate administered to male Swiss mice at a daily dose of I0 ~g for 5 days increased the hyaluronic acid content of the skin. This effect was observed in groups of mice ranging in age from i00 - 750 days and was, thus, not affected by the age of the animals.
A marked decrease occurs in hyaluronic acid (HA) and chondroitin sulfate (CS) contents of the skin of male mice with age (i). in the females is considerably less.
The change
Estradiol dipropionate at a dose
of 5 ~g daily for 5 days produced a ~arked increase in HA in the skins of young male mice (2).
It therefore seemed desirable
~o test the
effect of estradiol on male mice of different ages.
MATERIALS AND METHODS Male Swiss mice were obtained from c o ~ e r c i a l suppliers, and, after 3 weeks quarantine, were aged at this hospital. They were fed commercial rat pellets. T h e conditions of housing were less than desired. Mortality was 40% at one year of age and virtually 1007. by two years. Mice of 5 age catagories were selected for this experiment. A dose of i0 ~g of estradlol dipropionate in 0.I ml of sesame oil was injected daily, subcutaneously, for 5 days. Controls received oil alone. On the 6th day, the pelts were taken and the isolation and measurement of HA and CS were carried out as previously described (3). The results were expressed as hyaluronlc acid hexosamine and chondroitin sulfate hexosamine.
ST ER O I D S
16:1
RESULTS
~e
findings are shown in Table I.
HA wlth age.
Th'e data show a 28Z decrease in
Estradiol induced approximately a twofold increase in each
of the 5 groups ranging from the youngest to the oldest. decrease in CS with age.
Estradlol
There was 30Z
d i d not produce a s i g n i f i c a n t
increase
i n CS.
TABLE i Hyaluronic Acid Hexosamine (HAH) and Chondroltin Sulfate Hexosamlne (CSH) in the Total Skin of Male Swiss Mice of Various Age Following Estradiol Administration.
AGE (Days) i00=250
GROUP
NO, 15 17
WEIGHT START (g) 41.9 ± i.I* 41.7 ± 0.8
WEIGHT FINISH (~) 43.2 ± I.i 44.1 ± 0.7
}IAH (ug) 448 ± 55 1045 ± 76**
CSH (ug) 263 ± 19 314 ± 25
Control Treated
250-350
Control Treated
17 18
45.2 ± I.I 45.7 ± 1.0
45.8 ± 1.0 46.7 ± 1.0
447 ± 23 905 ± 66**
244 ± 15 276 ± 16
350-500
Control Treated
15 18
43.2 ± 1.7 44.4 ± I.i
44.0 ± 1.0 46.7 ± I.i
357 ± 28 769 ± 32**
224 ± 17 242 ± II
500-650
Control Treated
Ii 13
43.4 ± 1.6 46.4 ± 2.5
43.5 ± 1.7 47.5 ± 2.3
346 ± 24 618 ± 45**
223 ± 12 229 ± 18
Control 9 46.8 ± 3.3 47.2 ± 3.1 323 ± 28*** Treated 9 45.5 ± 1.4 45.3 ± 1.6 672 ± 56** Standard error. P < .001 compared wlth controls of same age. P < .02 compared with 250-350 day old group. P • ,01 compared with 2~0-350 day old group~
650-750 w-, ,_,_,_,
183 ± 14;~;4 204 ± 15
DISCUSSION It was earlier observed that a dose of 5 ~g estradiol dipropionate administered
to young mice (22 - 23 gms) resulted in a marked increase
in HA in the skin, a smaller dose and larger dose were less effective. The present daily dose of i0 ~g was used to accommodate weight of the older animals.
the greater
Since the "physiologic dose" of estradiol
for the mouse is usually taken to be less than .01 ~g, the present dose
July 1970
S T ER O I D S
is definitely "unphysiological".
Nevertheless,
3 the data show that t h e
oldest mice are markedly susceptible to the effect of estradiol on HA in the skin, although this effect is somewhat less than in the youngest group.
The increase in HA was about double while CS did not exhibit a
statistically significant effect. preparation,
Whatever the site of action of the
the findings suggest that age does not effect its delivery
to the fibroblasts nor the response of the latter to it.
ACKNOWLEDGMENT S This project was supported in part by Part I funds of the Veterans Administration, by NASA Grant NGR-05-O07-113, NSF Grant GB-662~ and by Navy Contract NOO014-67-A-OII-0008.
REFERENCES i.
Sobel, H., Hewlett, M. J., and Hrubant, H. E., J. GERONTOL., In press.
2.
Sobel, H., Lee, K. D., and Hewlett, M. J., BIOCHIM. BIOPHYS. ACTA, i01, 225 (1965).
3.
Sobel, H., Hewlett, M. J., Hoshek, S., and Sacker, I. Mo, AMXR, J. PHYSIOL., 212, 773 (1967).