Download - Age n Sebaceous Gland
-
7/26/2019 Age n Sebaceous Gland
1/4
0022-202X/79/ 7301-0108$02.00/0
TH E
JOURNAL
OF INVESTIGATIVE DERMATOLOGY, 73:108-111,1979
Copyright 1979 by The Williams Wilkins Co.
Vol.
73
, NO.1
Printed
ill
U S .A
Age related Changes in Sebaceous Gland
Activity
PETER
E.
POCHI, M .D., JOHN S. STRAUSS, M.D. , AND DONALD T DOWNING, PH.D.
Department
of
Dermatology University Hospital Boston Mass. U.S.A.
The sebaceous glands
of man
show age
-
related
differ
ences
in their
activity as determin ed
by
quantitative and
qualitative
examination
of sebum. Sebaceous
secretion
is low
in
children and begins to increase
in
mid
-
to late
childhood
under the
influence
of androgens. This rise
continues until
the late
teens,
after
which
no further
significant change takes place until
late
in
life.
In elderly
men,
sebum levels remain essentially un-
changed from
those of
younger adults until the age of
80. In
women, sebaceous secretion decreases gradually
after
menopause
and
shows no
significant change after
the
7th
decade. The most likely
explanation
for the de -
crease
in
sebaceous gland secretion with age
in
both
men and women is
a
concomitant decrease
in the endog-
enous
prod.uction
of
androgens.
Although surface lipid
levels
fall with
age,
paradoxi
cally
the sebaceous'
glands
become larger,
rather than
smaller, as a
result
of decreased
cellular
turnover.
None-
theless,
as the higher surface lipid
levels
after adminis-
tration
of fluoxymesterone
(a synthetic
testosterone
de -
rivative)
indicate, the glands have the
capacity
to re-
spond
to
androgens.
Sebaceous gland activity decreases with advancing age l l
The principal cause for this attrition appears to be diminished
hormonal
stimulation,
a
reversal
of the increase in glandular
activity that occurs
at
puberty through augmented elaboration
of androgenic steroids. This review is concerned with studies
on
sebaceous
gland
activity
in
the
aged
and the
correlation
of
these findings
with hormonal alterations
that occur in
late
middle age and senescence . Data are also presented
on
the
developmental changes
occurring from
the
time the glands
begin to mature to the time
they
reach
their
adult
state
.
METHODS
In our laboratories, sebaceous gland activity
is
measured
by
a method
[2]
that involves the absorption of surface lipids from a defined area of
the forehead onto absorbent papers for a period of 3 hr. The lipids
collected are extracted
by
ether and measured gravimetrically. The
determination of individuai lipid class components of forehead surface
lipids is made by thin-layer chromatographic separation and photoden
sitometric quantification [3].
SEBACEOUS GLAND
DEVELOPMENT
Human
sebaceous glands develop during fetal life between
weeks 13 and
15
of gestation; they
attain
fair size by the time of
birth
and then mostly
shrink
to comparatively small structures
during childhood [4]. With the onset of puberty and stimulation
by androgens, there is
glandular hyperplasia
and an increase in
the synthesis
and
secretion
of
sebum.
Studies
by Cotterill et al
Reprint requests to : Peter
E.
Pochi, M.D ., Department of Derma
tology, University Hospital , 75 E. Newton Street Boston, Mass. 02118.
This work was supported
by
U.S. Public Health Service grant IROI
HD11632 (National Institute of Child Health and Development).
Drs. Strauss and Downing are currently t the Department of
Dermatology, University of Iowa Hospitals, Iowa City, Iowa.
Abbreviations:
T, = thyroxine
T
=
triiodothyronine
TSH
=
thyroid-stimulating hormone (thyrotropin) .
108
comprising
cross-sectional
analyses
in
children
before
and
after
the age of 10, showed no increase in sebum secretion until
the
mid teens, except in
menarchal
girls, in whom
the
increase
was
evident somewhat earlier [5]. However, sebum production tests
we
performed
twice yearly in each of
9
boys and 6 girls for a
3-
yr period showed
an
earlier increase in
sebum
production .
Figure 1 illustrates our results. A gradual increment
in
the
amount
of
sebum
secreted
occurred; this increment became
somewhat more abrupt at
age 13. No obvious sex difference was
apparent, either in the quantity of sebum produced at any given
age
or
in
the
slope of
the
line
representing
sebum secretion.
In actuality, one can observe
an
even earlier increase in
sebaceous gland activity, before the age of 9 by determining
the
relative
composition of skin surface lipids, which are mix-
tures of sebaceous and epidermal lipids [6]. As sebum secretion
begins
to increase
in
late
childhood,
the
amount
of
wax
esters
,
which are of
sebaceous origin, increases relative to
the amounts
of
cholesterol and cholesterol esters, which are epidermal lipids.
One can show
that
the wax esters/[ cholesterol+cholesterol
esters] ratio increases
at
approximately 7
or
8
yr of
age and
these lipids approach an adult composition by age 10 or
[7,8].
Published
results of studies based on examinations
of
individ-
uals of different ages suggest
that
full sebaceous gland matu-
ration is not attained until either late in
the
2nd decade or early
in the
3rd
decade [4,5,9,10]. Figure 2 shows
data obtained
in a
13-yr longitudinal study
of
sebum secretion in 2 children, a bo y
and a girl. Sebum
production
was
measured
in each of the
children 4 times yearly. Secretion clearly increased
at
age 12
or
13,
continued
to
increase gradually
and
steadily until
age 17 or
18
and then appeared to
enter
a stable phase. Our
lack
of
evidence for an earlier sebum increase in the girl was in contrast
to
another
report [5] which indicated greater production in 11-
to 15-yr-old girls, especially menarchal ones.
SEBUM STUDIES
IN THE
AGED
Once
maturity
has been achieved, little change in sebaceous
gland
activity
takes place until
middle
age
and
thereafter . Table
I shows sebum production values in women and men 40 y or
older. Average sebum
production
levels in the women fell by
approximately
40% in the 6th decade, declined
additionally
in
the 7th decade, and
remained
constant thereafter. In the me n,
no change was observed until the 8th
decade
. At any age range
examined,
mean sebum
values
in
the men
exceeded
those
in
the women.
This
finding of a drop in surface
sebum
levels with
advancing age and of a greater decrease in women is in general
agreement
with
reports
of
other
studies [5,10-15]'
Reduced
sebaceous gland activity, as evidenced by lower surface lipid
levels, has also
been
demonstrated in vitro by diminished
formation
of squalene,
and to
a lesser extent of wax esters, from
glucose in skin biopsy samples from the backs
of
elderly men
[16]. .
Study
of
the
forehead surface lipid composition in 15 children ,
18 young
adult
women, and 10 postmenopausal women revealed
wax esters/[
cholesterol+cholesterol
esters]
ratios that
were low
in the children, high in the young adults, and low in the age d
women (Table II). These changes reflect the differences in
sebaceous
gland
activity occurring
at
these
various times
of
life.
The most probable explanation for the decrease in sebaceous
gland
synthesis
and secretion in the
aged
is a
concomitan
t
decrease in the production of androgens. In men, testosterone
-
7/26/2019 Age n Sebaceous Gland
2/4
July 1979
:J
o
r::
M
E
u
cr
fJJ
o
0
'is.
::;
Ol
1 .5
1 0
0 .5
I
9 10 11
AGE (years)
12
13
FIG 1.
Seb
um
production
in
15 children tested
tw
ice yea rly over a
-yr period. Height of each co lumn represents the mean sebum va
lu
e
he results obta
in
ed
at
the age when tested.
0
=
6 g
irl
s;
=
9
bo
ys.
3 .5
3 .0
;
2 .5
2 .0
1 .5
1 .0
0 .5
I
I
- l e I \
I
Female / \ _ - ,
I
/
I
- '
I
I
...
I
/
/ menarche )
7 8 9
10
11
12 13
14
15 16 17 18 19
2 0 21
22
AGE
FIG
2. Longi tudinal study of se bum production
111
th e skin of 2
human beings. - - - = male; - - = femal
e.
I.
Se bum production values
in
normal men and women 40 yr
of
ag
e and older
W
ome
n Men
Age
No
.
M
n
Range
No .
Mean
Range
40-49
3
1 1.86
0.12-4.80
50
2.39
0.54-5.14
50
-
59
21
1.08
0.07-2.38 14
2.43
1.05-4.36
60-69
18 0.88
0.22-1.62 14
2.42
0.83-4.95
70-79
12 0.85
0.33-2.19
13
1.
69
0.63-3.
23
Milligrams of lipid per 10 cm' of skin per 3 hI .
lood levels gradually decline after the 6th decade bu t do not
ignifica ntly
until
approximat ely the age
of
70 [1
7-20
].
hormone data corr ela te we ll
with
the finding of no
in se bum product ion l
eve
ls
until
after the age
of
70
,
On
other hand , studies have indicated that the fraction of free
osterone,
the pr
es
um
ed form in
which
testo
st e
ron
e
enters
e target ce ll , de creases at an earlier age, usually between 50
nd 60 yr [18- 20]. That
sebaceous
gland activity does
not
until
a de cade or 2 lat e r attests to the ma
rk
ed sensi
ty of t he gland to e
ndog
enous androgen stimulation ,
SEBACEOUS GLANDS IN THE AGED
109
TABLE II. Com
parison
at different oges ofwax esters/
[cholesterol clwlesterol ester
s
ratios in forehead s
ur f
ace lipids
No . subjects
Ratio
Children
15
0.
35
Young adul t
18
7.47
wom en
Postmenopau
sa
l 10 1.46
women
In
women, androgen so
ur
ces for sebaceous gla nd stimulation
are the
ovary
and
adr
ena
l cortex. We had ass
um
ed previously
that
the postmena
pausa
l
decrease
in
sebum
production h
ad
been the result
of
ovarian involu tion and that the failure
of
many
subjects to reach prepubertal se
bum
l
eve
ls had been du e
to
persistent
adrenocort ical and rogen secretion [4].
However,
subseq
uent
st
udies demon
strated
th
at postmenopausal
ovari
es
r
et a
in a considerab le
androgen
synthet ic
capac
ity,
In
postmen
opausal
women,
plasma testostero
ne l
eve
ls fall
after
bilateral
oophorectomy [
21
] and are lower in postmenopausal
oop
horec
tomized wom en than in no
rmal
con tro ls [22 ]. Mo reover, the
concent ration
of testosterone
in the
ovaria
n vein exceeds that
in
the per
ipheral
blood [23,24] and increases significantly after
administration
of
human chorionic gonadotropin [24]. However,
a
dr
enocortical a
ndrog
en
secretion mu
st also decr
ease
in women
(and me
n
with age since there is a gradual decr
ease
in urinary
17-ketosteroid excretion and plasma concen trations of
dehy
droepia
ncb
'osterone (the
prin
cipal adl'enal andl 'ogen) [25-27].
Valu
es
for
these
acb'enal andl'ogens are gr
eate
r in men than in
women, and this differential persists
un
t il a
very
late age,
after
which they
closely
approach
one
anot
her [25,28,29].
Alt hough it is probable that the diminished se baceous gland
secretory ac tivity occurring in the aged ca n largely be expla
in
ed
by
concomitant
changes in an drogen levels, th e possible role
of
such
ot
her hormones as glucocorticoids a nd thyroid hor mones,
mer its consideration, There is ev idence th
at
human sebaceous
glands req uire cor tisol for their
optimal
response to ancb 'ogenic
st
imul
at
ion [30].
Thu
s, if
imp
a
ir
ed end ogenous co
rt i
coid activ
ity
were
to occur
with
ag ing, this defect might l
ead
to a
blunted
sebaceo
us gland
response
to androgens,
Studies
have shown a
dec reased clearance
rat
e of cortisol in the aged [31,32] and less
urin
ary excretion
of
17-ketogenic st eroids [27,33] a nd cortisol
metabo li tes [32], but
thes
e changes
are
n
ot marked
and
are
the
sa me for bo th sexes [33 ]. Moreover, other indicators of adre
nocort ical function, such
as
pl
as
ma cor tisol l
eve
ls, urinary free
cor tisol excretion ,
diurn
a l
va
riation, a
nd
r
espo
nse
to
ACTH
stimulation , ar e essentially the sa me in the elde
rl
y and the
yo un
ger
ad ul t [33]. Because t he se baceous glands would not be
aff
ecte
d by a less
than seve
re a
dr
en
ocort
ical insufficiency, it is
unlikely t
hat
the
mod
est a lte ration s in acb'enocortical fun ction
in the aged can accoun t fo r
or
even co
ntribu
te to the
compa
r
at
ively low
sebum
l
eve
ls
of se
nescence,
Studies have suggested a role for t hyroid h
or
mones in the
ma in tenance of se baceo us gland fun ct ion,
Th
yroidectomy in
rats
pro
du
ced significa nt re
du
ct ions in
sebum
secretion, a
nd
thyroxine (T.) administrat ion restored secretion [34]. Seb
um
produ
ct ion levels were found to be lower in p
eop
le with hypo
thyroidism
than
in
norm
a l co
ntrol
s, and treatment
with
L
thyroxine was followed by an increase in sebum produ ct i
on
in
the hypothyroid patients [35]. Alt
hou
gh in elderly men
plasma
total and free T . conce
nt r
at
ion
s are normal, as is the concen
tration of
protein-bound iodine, the metabolic
cl
earance rate
of
T is re
du
ced, pr es
um
ably a reflection
of
a decreased T., pro
duction r
ate,
Also, pla sma tr iiodothyronine T ,) levels are
lower, probably b
eca
use
of dimini
shed p er
iph
eral conve rsion of
T.,
to
Tl'
No
major sex diff
ere
nces in
thyroid abnormalities
have been no te d, a lthough iso lated studies have reported in
men a lessened t h
yrotro
pin
(TSH)
r
espo
nse to
TSH-releasing
hormone administration and low
er
plasma T , level
s,
As to the
relationship between
thes
e thyroid a lte r
at
ions in aging and the
-
7/26/2019 Age n Sebaceous Gland
3/4
110
POCH
I , S
TR AUSS,
A
ND DOWN
I N G
sebaceous gla
nd
s, it is ent irely possible that the decreased
thyroid fun ction t h
at
occm s with aging has a depressive influ
ence
on
sebaceous lipid synthesis.
Howeve
r, the cha nges de
scr
ibed above are
n
ot
part
ic
ul
ruly ma rked, a
nd
there are con
trad
ictory data conce rning them [36].
I t
is
un l
ike
ly th
at
any
signifi
ca
nt effect is
exerted
since men
are
m
or
e apt to have
d
ecrease
d th
yro
id
ac t
ivi
ty
in
se
nescence a
nd yet they
ma inta in
un
changing seb
um
l
eve
ls
un
t il
at
least the age
of
7U.
SEBACEOUS GLANDS IN T HE AGED
Alt hough, as described in the preceding
sect
ion, t he quantity
of surface Li pids in skin areas where sebaceous gla nds are
nor ma lly ab
und
ant
decreases
with age, P lewig.
and
Kligman
have recently demonstrated by pla nim etric
stu
dy that the
gl
ands
ac tua lly become larger ra th
er
than sma
er
[37]. T hi s
effect
is t he opposite
of
what one migh t
expect
to occm in a
holocrine-secret ing gla
nd
. Actually, Lee had ea rlie r
obse
rved
striki ng hypertro
ph
y and hyperpl
as
ia of the sebaceous glands
in t he foreh
eads of
9
me
n over t he age
of
40 [38]. Ho wever , in
a s ubsequent in
vest
igation, Ka Llapravi t, wh o st udied fewe r sub
jects,
fo
und
th
at
gla nds in age d
me
n we re the
sa
me s ize as t hose
in yo un g
adu
lt
me
n [39].
Tab le
II
I shows data from the study by P lew ig a nd Kligma n
in which t he s ize
of
the se baceous gla
nd
s
in
me
n
in
cr
ease
d wit h
age. I n 3 groups
of
men
of
differe nt ages, ad di tiona l com
pa
r
at
ive
measurements were made of the re l
at
ive volu
me
of skin occu
pi
ed
by the glands in the rem
oved
t i
ssue
spec i
me
n and of the
l
argest
gland
obse
rved in
eac
h
spec
imen. T h
ese
2 indices were
al
so
greater in the elder ly t ha n in t he
yo un
g. T hese investigators
injected t rit iated thym idine a
nd
hi
stid
ine in
trac
uta neo usly in
order
to st udy se baceous gland
ce
llular kin
et
ics. T h
ey
obse rved
reduced cell tmn
over
in the aged gla
nd
s a nd slowe d m ovemen t
of
t he radiolabeled sebaceous ce lls. P r
es
uma bly, t he large size
of
the gla nds w
as
the resul t
of
prolonged ce ll tr ansit t
im
e, in
t he face of continu ed sebaceous lipid synth
es
is. Th is assum
pt
ion
would be consistent wi th the obse rv
at
ions, desc
rib
ed a bove, of
no m
ea
n decrease in surf
ace
lipids in men un der
70
yr
of
age.
However,
the authors, without presenting sp
ec
ific
informat
ion,
me ntion that the se baceous gla
nd
s of elde rly women are simi
lar ly enlarged,
eve
n though se
bum
l
eve
ls are su
bsta
nt ially lower
in
p o s t m ~
women.
In
women,
Lee
did n
ot
find the
se baceous glands to be enlarged, as she did in men
[38].
Sebaceous gland hype
rpl
as ia wi th decreased ce ll t
urn
over,
does not rende r
sebaceo
us gla
nd
s un r
es
ponsive
to
a
ndr
oge nic
st imul
at
ion.
St
udi
es
have demonst ra ted the
ca
pac ity of age d
seb
aceous
gLa
nd
s,
in
both men a
nd
women, to
res
po
nd
to
testostero
ne a
dmini
st
ra t
ion [15,40,41]. F luoxym
este
rone
ca
n
also st imulate postmenopausal sebaceous gla
nd
s (Tab le IV).
T
hu
s, despite t he f
mdin
g th
at
histologi
ca
lly t hey become en
lruged in t he el
de
rly, these gla
nd
s are
res
ponsive
to
horm onal
st imul
atio
n, insofa r
as
detection by surf
ace
lipid
measur
emen
ts
is co nce
rn
ed. I t would be of in terest to
kn
ow wh ether such
treat
ment ca n rend
er
the h
ype
rpl
as t
ic gla nd s sm
alle
r by in
cr
eas
ing cell tUjnover.
Whatever the r
easo
ns for th e hyperplas ia a
nd
d
ec
reased
ac tivity
of
aged
sebaceo
us glands, there are no obvious mor-
ph ologi
ca
l abnormaliti
es
of individual sebaceous
ce
lls [37,42].
However, clusters of
undiffere
ntiat ed ce lJs
ca
n ofte n be
see
n
ar ising from the follicular epi the
lium
of seb
aceo
us follicl
es
.
T BLE
I l l
.
Planimet
ric meas
ur
eme
nt of
sebaceous gland size in
facial biopsy specimens from men
Age
No. subj ec ts
M
ean
cross-secLiona l
area
(mm ' )
20-36
15
.2258
47-53 5 .2532
64-74
21 .4003
Ad
apted from Plewig and Kli gman, Invest Derm alol 70:314 1978
[37].
Vol. 73, N O.1
Although undifferentiated
ce
l s do not r e
pr
ese
n t a spec ific
senescent cha nge, t h
ey
do occ
ur
in great er nu mbe rs tha n llt
yo
un
ge r individ
ua
ls [42]. Unl ike no
rm
al se baceous ce lls, w h
ich
rue strongly r
eact
ive for succ inic dehydrogenase, th
ese
un dif.
fe rentiating cell
rests
show li ttle
reactiv
ity fOl this enzym e.
BREAST C
AN
CER IN
PO S
TME N
OPAUSAL
WOME N
In
a prev ious ar ticle, we reporte d th
at
sebum production,
levels in p
os t
menopa u
sa
l women with breast
ca
ncer were s i
g.
nifi
ca
ntly higher than in age-m
atc
hed controls [43]. Su
bs
e
quent ly, 2 other groups reached the sa me conclusion after
similru
st ud
y
[44,45].
Because pl
as
ma testosterone a nd de h
y_
d
roep
ia
ndros
terone sul
fate
l
eve
ls a re not high
er
in
br
east cancer
patien ts [45,46] nor do such patients become virilized or show
differences in
testoste
rone metabolism as compa red to normal
w
ome
n [
47
] , t
hi
s greate r
sebaceo
us gla
nd
ac tivi
ty
h
as
no ready
expla n
at
ion. Goolam ali and Shu st er suggested the possibility
th
at
a
sebotro
pic f
acto
r mi gh t be pr
ese
n t in pat ien ts with cancel
and migh t be ma
mm at
ropic
as
we ll , for b
ot
h maligna nt
and
beni gn breast di
sease
[48].
Howeve
r , since om origina l report of se bum produ ct ion lev el
in
22
br
east ca
nce r p
at
ients, we h
ave
st udi ed a n addi tional 50
patients, all postmenopausal wit h no previous e
nd
ocrin e surgi.
ca
l in
te
r
ve
ntions or hor
mo
na l t herapy for t heir di
sease
,
and
have com
pared
th
eir
se
bum
l
eve
ls with t h
ose
of a n age- mat ch ed
no
rm
al gro
up
of
51
women. In
eac
h perso n, se bum produ ct ion,
tests were per fo r
me
d on 3 separate
occas
ions. Tab le V shows
the r
es
ul
ts of
o
ur
ini tial
stud
y,
res
ul ts from s
ub
se qu ent reports
by other investi
gato
rs, and our curr ent data . Originally we h ad
fo
und
the mean se bum
pro
du ct ion level for breast
ca
n
cer
pa.
t ien
ts
to be more t han double th
at
of the control gro
up
,
bu
t
We
s
ub
se qu en tly found the difference to be only 25
%
a nd no t
statisti
ca
lly s ignifi
ca
nt (p
>
.1. One might postulate th
at
th er
was a s
ub
gro
up
of
br
east
ca
n
cer
p
at
ien ts wh o fa
il
ed to e
xhi bi
t
the l
owere
d se
bum
levels of aging women, but this
ph
en
omenon
was not characteristic for the gro
up
as a whol
e.
PHYSIOLOGICAL SIGNI FICAN CE OF
SE B
ACEOUS
G
LAND
IN
VOLUT ION
Th e red u
ct
ion in se b
aceo
us gla
nd
ac t
ivity th
at
normally
occurs wit h aging rai
ses
the ques tion
of
wheth
er
SLi ch an invo_
T
BLE IV. E
ff
ect of fl
uoxy
mesterone
on
sebum p r
od
uct ion i
n eight
postmenopausal wom.en
Dose
Sebum pro ci uc lio
l
(mg / l0 cm ' or
hr)
10
mg/ day
Mea.
n
20
mg
/ day
ean
Ages 52 to 67.
0.81
1.26
1.61
1.
23
1.20
1.
34
1.53
1.78
2.38
1.
65
IcaLmen l
1.83
1.62
1.77
1.74
1.47
2.35
l.
89
2.17
2.72
2. 12
T BLE V. Sh
in.
su
rface lipid m
easur
ements in postmenopausal
wome
n
with breast cancer
reast c
n
e l
Kra
nt et al [
43
] 2.11 (22)
Burton et
aJ
[44] I l 0 (20)
W
ang
et
al
[
45
] 0.37 (1
9)
C
urr
ent study 1.29 (72)
Milligrams per 10 cm
2
of skin per 3 hr.
Numbers of subj ects me in pa rentheses.
Normal
s
1.02 (31)
0.76 (20)
0.
24
1
9
0.96 (51)
P value