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Hair Growth Cycle in Subcutaneous Implants of Skin*
HAIR GROWTH CYCLE IN SIJBCIITANEOTJS IMPLANTS OF SKIN* A. E. FRIEDMAN-KIEN, M.D., C. J. DAWE, M.D.t AND E. J. VAN SCOTT, M.D.
The critical stages of hair development and the associated skin changes in the mouse have been well described (1, 2, 3). The term anagen has been applied to the period of active prolif-
eration of the pilo-sebaceous unit which in
the nearest day from the time of mating, indicated by the vaginal plug technic. A total of 20 fetuses were aseptically removed from the uterus of ether-anesthetized pregnant females. After separation of the fetuses from their fetal membranes
the skin over the dorsum of the back of each the mouse lasts for about 17 days. The mouse fetns was excised and washed in a sterile petri containing Morgan, Morton, and Parker's is born with the hair enteriug its first cycle. dish Mixture 199t supplemented with 2% fetal calf Hair growth ceases at the age of 17 days, passes serum, at room temperature. The skin was then through the involutional phase of "eatagen" transferred to a deep-well culture dish containing duriug the l7th—l9th day, and enters the rest- the same media and with the aid of a dissecting ing phase known as the "telogen". The latter microscope and a pair of sterile cataract knives the skin was divided into specimens approximately phase persists for approximately 10 days and 1.0 mm sq. at the end of this time a new cycle of anagen Capillary pipettes were used to transfer the begins which in turn is again terminated at skin pieces to a subcutaneous site in newborn approximately the 45th day of life. The phase isologous hosts. A small incision was made in the neck skin overlying the dorsal mid-line. The tip of telogen occurring at this time, however, and of the pipette, containing three skin pieces, was those thereafter, persist for varying and pro- inserted through the incision and a tract forced longed periods, even though the length of ana- through the subcutis over the spine to the base of the tail. As the pipette was withdrawn the gen remains the same. of fetal skin were gently blown out The influences controlling this cyclic pattern fragments of the pipette and deposited at intermediate points of hair growth are not yet understood. Systemic along the course of the subcutaneous tract. When a serum clot had formed over the neck hormones (4, 5), diet (6), and general health
are known to influence growth of hair; but incision, each recipient animal was returned to its
experimental evidence suggests that the essen- mother. At weaning age males and females were caged separately. A total of 70 male and female
tial factors that determine the hair growth newborn animals were used as recipients. The 19cycle are inherent in the skin itself.
day fetuses of three pregnant females supplied the
The present experiment was designed to donor skin. At periodic intervals one or more anistudy the development of hair in fetal mouse skin (19th day of gestation, about 1 day prior to term) subcutaneously implanted into isologons newborns. In this way the implants were placed in an environment isolated from that of the host skin, while at the same time being
mals were killed, the pelt dissected away, and the status of the implants grossly and histologically ascertained. Histologic preparations were stained
exposed to identical systemic influences.
cular supply in almost every host. Very few animals did not possess viable implants. With
MATEaIAL5 AND METHODs
by the Comori trichrome method. OB5EavATION5
The implants established a recognizable vas-
the appearance of pigmented hairs, it was easy All mice used in these experiments were from to visualize the implants even though they the National Institutes of Health Animal Production Laboratory's stock of the C57 BL/6 strain. were always found surrounded by adipose Donor skin was taken from 18—19 day fetuses (1—2 tissue. The implanted specimens increased from
days prior to birth). The age was calculated to their original size of 1 mm at the time of transplant to as large as 6 mm in diameter by Presented at the Twenty-fifth Annual Meeting the 74th day. In almost all animals, pigof The Society for Investigative Dermatology, mented anagen bulbs were easily discernible in Inc., San Francisco, California, June 21, 1964. * From the Dermatology Branch, National Cancer Institute, National Institutes of Health, Be- the implants by means of a dissecting microthesda, Maryland. Public Health Service, U. S. scope; this was confirmed by histologic analysis.
Department of Health, Education and Welfare. t Laboratory of Pathology, National Cancer Int Obtained from Microbiological Associates, stitute. Bethesda, Maryland. 445
446
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
All implants tended to form a cystic structure early in the experiment. The epidermal portion of the implant skin curled around to form the inner layer of the cyst into the sac of which the stratum corneum was shed. The dermis containing the hair follicles surrounded the epidermal layer and the hair follicles produced mature hairs which grew into the cyst
attained a maximum length of 6 mm by day 60. This was approximately the same as the maximum length grown by the host's dorsal skin during the second cycle of anagen.
The comparative sequences of the hair cycle in the implant and host skin are seen in Table I.
In the host skin the first anagen phase was found to be complete by the 17th day. By and formed a bolus of hair tightly contained the 28th day the second anagen phase had
within the sac. Such hairs were mierodisseeted free and upon measurement were found to have
started, which terminated in the second telogen
by the 45th day. Except for one host skin specimen examined on day 60 in which a wave
TABLE I
of anagen and telogen hairs was found host
Growth cycles of host skin and implant
skin in all other instances was found to remain in telogen from day 45 through the 102nd day
Day (Age of float)
5 8 11
Anagen
Implant Implant Implant
13
14 17 19
20 24
28 29
30* 35 36 38 39 43 45 46 50 52 53* 57*
60f 61 62 65 69 70 74
83t 85t 93t 102t 109t
Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant
Implant Implant Implant
Telogen
than the host skin, remained in an anagen
Host Host Host Host Host Host Host
Host Host Host Host Host Host Host Host Host Host
Host
Implant Implant Implant
Host Host
when a 3rd onset of anagen activity was detected. The implanted skin, one day younger phase of the growth cycle for 74 days. During this time, mitotie activity was present in the matrix of the implanted anagen hair bulbs. At no time were eatagen or telogen follicles seen in the implanted skin. Instead, at 74 days and thereafter the hair follicles of the implant underwent what seemed to be a compression atrophy resulting from distention of the cyst by stratum
eorneum and hair shafts. Figures 1—12 show the sequence of events observed.
nIseussIoN
The major finding of this study, namely that anagen was experimentally extended for a peHost Host Host Host Host Host Host Host Host Host Host Host Host Host Host Host Host
* Non-survival of implant.
t Growth wave in host skin. Compression atrophy of hair roots of implant.
riod far longer than the normal, does not in itself provide direct information on what factor(s) control the hair growth cycle. It does, however, permit another re-evaluation of factors possibly operative in such control and suggests
further studies which might be done to secure more definitive information in this regard.
The ancillary observations of this study, that the length of hair shaft produced by the follicles of the implant did not exceed the length
of hair produced by the follicles of the host skin, suggest that each follicle may he endowed at the onset of anagen with a growth potential
that permits a fixed amount of growth and no more. The rate at which this potential is realized, i.e. the time for anagen to reach completion, may then by regulated by other means
such as nutritional factors provided by, for example, blood supply. There is some support for this notion in experiments with mice where
447
HAIR GROWTH CYCLE IN SUBCUTANEOUS IMPLANTS OF SKIN
iL f J— 1sj
—
—
—
- 't: a—. _'zt. --;
-r
———7 j__ .t•__t_
'_7 1.r
r'
4:-'
fl
-. - -
•1 '%%. ____ -
.
Fin. 1. Skin of 19-day fetal mouse, showing state of hair follicle development at the time such specimens were subcutaneously implanted into newborn isologous animals. X 117.
Fin. 2. Day 11 after implantation. Hair of both the implant (centrally located) and host skin (circumferentially located) is in anagen phase. Implanted skin has already formed a cyst into which hair grows and stratum corneum accumulates. X 55. Fm. 3. Day 14. Hair roots of implant (lower half of photo) growing in panniculus carnosus. Follicles of host skin (upper half of photo) also in anagen. X 53.
it was found that caloric restriction prolonged peried of anagen in this experiment, it might their period of anagen, with the rate of hair also be speculated that the reason telogen did growth diminished accordingly (6). Although not come about at any time was due to the the animals in our study received an ad libitum same lack. If one reviews the sequence of histodiet, it cannot be assumed that nourishment logic and cytologic events during the process of of the implants was optimal—and in fact the cataqen, one cannot but conclude that the final atrophy of hair bulbs 74 days old and older transition of anagen to telogen is a dynamic, would indicate a gradual compromise of nourish- highly organized, directional process and that is nof a negative process of simple atrophy or ment accounted for this. Along this same line of thought, i.e. that im- degeneration of the anagen root. That is, it seems paired nourishment accounted for the prolonged quite likely that initiation and completion of
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
448
n
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-
lr: -- --
-
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--—-
V
•flu. 4. Day 19. Follicles of host skin (upper portion of photo) have entered telogen phase of cycle, whereas follicles of implant (lower portion of photo) continue in anagen. X 53. flu. 5. Day 20. Follicles of implant maintain state of anagen. X 53 Ftc. 6. Day 28. Follicles of host skin (upper half of photo) have entered anagea phase of 2nd growth cycle. Follicles of implant continue in anagen as before. X 53.
the process of catagen requires energy and that factors influencing hair growth would still metabolic regulation, perhaps as much so as operate in the presence of, or through the mediathe growth process of anagen.
tion of, this component.
The observations of the present study seem also compatible with the hypothesis of a spe-
SITMMAaY
cific anagen inhibitor accounting for telogen, as
Skin of 18-day fetuses of C-57 mice was imhas been proposed by Chase (7). Such an in- planted into subcutaneous tissue of isologous hibitor might not accumulate in sufficient newborns and excised at sequential intervals quantity in small subcutaneous implants as thereafter up to 109 days. During this period employed. In this regard, therefore, mass of hair follicles of the implants remained in the tissue may be important, much as in the reverse situation where it has been found in the mouse that at least 1000 telogen hairs must be plucked
anagen phase of the growth cycle, whereas those of the host skin underwent at least two complete cycles. Contribution of this finding to an under-
in order to permit initiation of anagen (7). standing of factors controlling hair growth is This hypothesis might be tested by studying
discussed.
the hair cycle in subcutaneous implants of pieces
REFERENCES
of skin larger than those used in the present
1. DRy, F. W.: The coat of the mouse (Mus musculus). J. Genetics 16: 287, 1926. The role of subcutaneous fat as a possible 2. CHASE, H. B.: Growth of the hair. Physiol. source of stimulus for anagen perhaps should not Rev., 34: 113, 1954. be disregarded. The fact that hairs grew well 3. ANDREASEN, E.: Cyclic changes in skin of the experiment.
in implants imbedded in skeletal muscle, might be thought to weaken an argument for such a likelihood. However, in this experiment the skin explants carried their own subcutaneous fat, so
mouse. Acta Path. et Microbiol. Scandinav.,
32: 157, 1953. 4. BAKER, B. L.:
Relationship of the adrenal, thyroid and pituitary glands to the growth of hair. Ann. N. Y. Acad. Sci., 53: Art. 3: 690,
1951.
449
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-r
-S
I:
JWsa'
,sr
HAIR GROWTH CYCLE IN SUBCUTANEOUS IMPLANTS OF SKIN
FIG. 7. Day 35. Persistence of anagen state by follicles of implant. >< 53
FIG. 8. Day 60. Follicles of implant in skeletal muscle in anagen. X 53 FIG. 9. Day 70. Host skin in second telogen phase of cycle (since approximately day 45). Hair roots of implant however are still in initial anagen phase. X 53. FIG. 10. Day 74. Hair roots of implant (lower portion of photo) maintain anagen structure while host skin (upper portion of photo) remains in telogen. Very few mitoses discernible in hair roots of
implant at this time. X 85.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
450
"lt: 't'' --e
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i'" ---r 7! --
-— --
'I.S - - • •e— a FIG. 11. Growth wave in host skin at day 60, an isolated observation. X 53 FIG. 12. Implant at day 74. This specimen shows hair root of the implant to be atropbic, although anagen structure is maintained. Atrophy seems to be caused by compression of root secondary to enlargement of cyst. All later specimens were found to be similarly atrophic.
5. D.&vis, B. K.: Quantitative morphological studies upon the influence of the endocrine system on the growth of hair by white mice. Acta Endocrinologica, 44: Supplement 85. Periodica, Copenhagen, 1963.
6. LOWENTHAL, L. A. ANO MONTAGNA, W.: Effects
of coloric restriction on skin and hair growth
in mice. J. Invest. Derm., 24: 429, 1955. 7. CIIASE, II. B. AN0 EATON, C. J.: The growth of hair follicles in waves. Ann. N. Y. Acad. Sci., 83: 365, 1959.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.
The critical stages of hair development and the associated skin changes in the mouse have been well described (1, 2, 3). The term anagen has been applied to the period of active prolif-
eration of the pilo-sebaceous unit which in
the nearest day from the time of mating, indicated by the vaginal plug technic. A total of 20 fetuses were aseptically removed from the uterus of ether-anesthetized pregnant females. After separation of the fetuses from their fetal membranes
the skin over the dorsum of the back of each the mouse lasts for about 17 days. The mouse fetns was excised and washed in a sterile petri containing Morgan, Morton, and Parker's is born with the hair enteriug its first cycle. dish Mixture 199t supplemented with 2% fetal calf Hair growth ceases at the age of 17 days, passes serum, at room temperature. The skin was then through the involutional phase of "eatagen" transferred to a deep-well culture dish containing duriug the l7th—l9th day, and enters the rest- the same media and with the aid of a dissecting ing phase known as the "telogen". The latter microscope and a pair of sterile cataract knives the skin was divided into specimens approximately phase persists for approximately 10 days and 1.0 mm sq. at the end of this time a new cycle of anagen Capillary pipettes were used to transfer the begins which in turn is again terminated at skin pieces to a subcutaneous site in newborn approximately the 45th day of life. The phase isologous hosts. A small incision was made in the neck skin overlying the dorsal mid-line. The tip of telogen occurring at this time, however, and of the pipette, containing three skin pieces, was those thereafter, persist for varying and pro- inserted through the incision and a tract forced longed periods, even though the length of ana- through the subcutis over the spine to the base of the tail. As the pipette was withdrawn the gen remains the same. of fetal skin were gently blown out The influences controlling this cyclic pattern fragments of the pipette and deposited at intermediate points of hair growth are not yet understood. Systemic along the course of the subcutaneous tract. When a serum clot had formed over the neck hormones (4, 5), diet (6), and general health
are known to influence growth of hair; but incision, each recipient animal was returned to its
experimental evidence suggests that the essen- mother. At weaning age males and females were caged separately. A total of 70 male and female
tial factors that determine the hair growth newborn animals were used as recipients. The 19cycle are inherent in the skin itself.
day fetuses of three pregnant females supplied the
The present experiment was designed to donor skin. At periodic intervals one or more anistudy the development of hair in fetal mouse skin (19th day of gestation, about 1 day prior to term) subcutaneously implanted into isologons newborns. In this way the implants were placed in an environment isolated from that of the host skin, while at the same time being
mals were killed, the pelt dissected away, and the status of the implants grossly and histologically ascertained. Histologic preparations were stained
exposed to identical systemic influences.
cular supply in almost every host. Very few animals did not possess viable implants. With
MATEaIAL5 AND METHODs
by the Comori trichrome method. OB5EavATION5
The implants established a recognizable vas-
the appearance of pigmented hairs, it was easy All mice used in these experiments were from to visualize the implants even though they the National Institutes of Health Animal Production Laboratory's stock of the C57 BL/6 strain. were always found surrounded by adipose Donor skin was taken from 18—19 day fetuses (1—2 tissue. The implanted specimens increased from
days prior to birth). The age was calculated to their original size of 1 mm at the time of transplant to as large as 6 mm in diameter by Presented at the Twenty-fifth Annual Meeting the 74th day. In almost all animals, pigof The Society for Investigative Dermatology, mented anagen bulbs were easily discernible in Inc., San Francisco, California, June 21, 1964. * From the Dermatology Branch, National Cancer Institute, National Institutes of Health, Be- the implants by means of a dissecting microthesda, Maryland. Public Health Service, U. S. scope; this was confirmed by histologic analysis.
Department of Health, Education and Welfare. t Laboratory of Pathology, National Cancer Int Obtained from Microbiological Associates, stitute. Bethesda, Maryland. 445
446
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
All implants tended to form a cystic structure early in the experiment. The epidermal portion of the implant skin curled around to form the inner layer of the cyst into the sac of which the stratum corneum was shed. The dermis containing the hair follicles surrounded the epidermal layer and the hair follicles produced mature hairs which grew into the cyst
attained a maximum length of 6 mm by day 60. This was approximately the same as the maximum length grown by the host's dorsal skin during the second cycle of anagen.
The comparative sequences of the hair cycle in the implant and host skin are seen in Table I.
In the host skin the first anagen phase was found to be complete by the 17th day. By and formed a bolus of hair tightly contained the 28th day the second anagen phase had
within the sac. Such hairs were mierodisseeted free and upon measurement were found to have
started, which terminated in the second telogen
by the 45th day. Except for one host skin specimen examined on day 60 in which a wave
TABLE I
of anagen and telogen hairs was found host
Growth cycles of host skin and implant
skin in all other instances was found to remain in telogen from day 45 through the 102nd day
Day (Age of float)
5 8 11
Anagen
Implant Implant Implant
13
14 17 19
20 24
28 29
30* 35 36 38 39 43 45 46 50 52 53* 57*
60f 61 62 65 69 70 74
83t 85t 93t 102t 109t
Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant Implant
Implant Implant Implant
Telogen
than the host skin, remained in an anagen
Host Host Host Host Host Host Host
Host Host Host Host Host Host Host Host Host Host
Host
Implant Implant Implant
Host Host
when a 3rd onset of anagen activity was detected. The implanted skin, one day younger phase of the growth cycle for 74 days. During this time, mitotie activity was present in the matrix of the implanted anagen hair bulbs. At no time were eatagen or telogen follicles seen in the implanted skin. Instead, at 74 days and thereafter the hair follicles of the implant underwent what seemed to be a compression atrophy resulting from distention of the cyst by stratum
eorneum and hair shafts. Figures 1—12 show the sequence of events observed.
nIseussIoN
The major finding of this study, namely that anagen was experimentally extended for a peHost Host Host Host Host Host Host Host Host Host Host Host Host Host Host Host Host
* Non-survival of implant.
t Growth wave in host skin. Compression atrophy of hair roots of implant.
riod far longer than the normal, does not in itself provide direct information on what factor(s) control the hair growth cycle. It does, however, permit another re-evaluation of factors possibly operative in such control and suggests
further studies which might be done to secure more definitive information in this regard.
The ancillary observations of this study, that the length of hair shaft produced by the follicles of the implant did not exceed the length
of hair produced by the follicles of the host skin, suggest that each follicle may he endowed at the onset of anagen with a growth potential
that permits a fixed amount of growth and no more. The rate at which this potential is realized, i.e. the time for anagen to reach completion, may then by regulated by other means
such as nutritional factors provided by, for example, blood supply. There is some support for this notion in experiments with mice where
447
HAIR GROWTH CYCLE IN SUBCUTANEOUS IMPLANTS OF SKIN
iL f J— 1sj
—
—
—
- 't: a—. _'zt. --;
-r
———7 j__ .t•__t_
'_7 1.r
r'
4:-'
fl
-. - -
•1 '%%. ____ -
.
Fin. 1. Skin of 19-day fetal mouse, showing state of hair follicle development at the time such specimens were subcutaneously implanted into newborn isologous animals. X 117.
Fin. 2. Day 11 after implantation. Hair of both the implant (centrally located) and host skin (circumferentially located) is in anagen phase. Implanted skin has already formed a cyst into which hair grows and stratum corneum accumulates. X 55. Fm. 3. Day 14. Hair roots of implant (lower half of photo) growing in panniculus carnosus. Follicles of host skin (upper half of photo) also in anagen. X 53.
it was found that caloric restriction prolonged peried of anagen in this experiment, it might their period of anagen, with the rate of hair also be speculated that the reason telogen did growth diminished accordingly (6). Although not come about at any time was due to the the animals in our study received an ad libitum same lack. If one reviews the sequence of histodiet, it cannot be assumed that nourishment logic and cytologic events during the process of of the implants was optimal—and in fact the cataqen, one cannot but conclude that the final atrophy of hair bulbs 74 days old and older transition of anagen to telogen is a dynamic, would indicate a gradual compromise of nourish- highly organized, directional process and that is nof a negative process of simple atrophy or ment accounted for this. Along this same line of thought, i.e. that im- degeneration of the anagen root. That is, it seems paired nourishment accounted for the prolonged quite likely that initiation and completion of
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
448
n
#t
-
lr: -- --
-
_ts, --
--—-
V
•flu. 4. Day 19. Follicles of host skin (upper portion of photo) have entered telogen phase of cycle, whereas follicles of implant (lower portion of photo) continue in anagen. X 53. flu. 5. Day 20. Follicles of implant maintain state of anagen. X 53 Ftc. 6. Day 28. Follicles of host skin (upper half of photo) have entered anagea phase of 2nd growth cycle. Follicles of implant continue in anagen as before. X 53.
the process of catagen requires energy and that factors influencing hair growth would still metabolic regulation, perhaps as much so as operate in the presence of, or through the mediathe growth process of anagen.
tion of, this component.
The observations of the present study seem also compatible with the hypothesis of a spe-
SITMMAaY
cific anagen inhibitor accounting for telogen, as
Skin of 18-day fetuses of C-57 mice was imhas been proposed by Chase (7). Such an in- planted into subcutaneous tissue of isologous hibitor might not accumulate in sufficient newborns and excised at sequential intervals quantity in small subcutaneous implants as thereafter up to 109 days. During this period employed. In this regard, therefore, mass of hair follicles of the implants remained in the tissue may be important, much as in the reverse situation where it has been found in the mouse that at least 1000 telogen hairs must be plucked
anagen phase of the growth cycle, whereas those of the host skin underwent at least two complete cycles. Contribution of this finding to an under-
in order to permit initiation of anagen (7). standing of factors controlling hair growth is This hypothesis might be tested by studying
discussed.
the hair cycle in subcutaneous implants of pieces
REFERENCES
of skin larger than those used in the present
1. DRy, F. W.: The coat of the mouse (Mus musculus). J. Genetics 16: 287, 1926. The role of subcutaneous fat as a possible 2. CHASE, H. B.: Growth of the hair. Physiol. source of stimulus for anagen perhaps should not Rev., 34: 113, 1954. be disregarded. The fact that hairs grew well 3. ANDREASEN, E.: Cyclic changes in skin of the experiment.
in implants imbedded in skeletal muscle, might be thought to weaken an argument for such a likelihood. However, in this experiment the skin explants carried their own subcutaneous fat, so
mouse. Acta Path. et Microbiol. Scandinav.,
32: 157, 1953. 4. BAKER, B. L.:
Relationship of the adrenal, thyroid and pituitary glands to the growth of hair. Ann. N. Y. Acad. Sci., 53: Art. 3: 690,
1951.
449
Jn -
-r
-S
I:
JWsa'
,sr
HAIR GROWTH CYCLE IN SUBCUTANEOUS IMPLANTS OF SKIN
FIG. 7. Day 35. Persistence of anagen state by follicles of implant. >< 53
FIG. 8. Day 60. Follicles of implant in skeletal muscle in anagen. X 53 FIG. 9. Day 70. Host skin in second telogen phase of cycle (since approximately day 45). Hair roots of implant however are still in initial anagen phase. X 53. FIG. 10. Day 74. Hair roots of implant (lower portion of photo) maintain anagen structure while host skin (upper portion of photo) remains in telogen. Very few mitoses discernible in hair roots of
implant at this time. X 85.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
450
"lt: 't'' --e
t -.
i'" ---r 7! --
-— --
'I.S - - • •e— a FIG. 11. Growth wave in host skin at day 60, an isolated observation. X 53 FIG. 12. Implant at day 74. This specimen shows hair root of the implant to be atropbic, although anagen structure is maintained. Atrophy seems to be caused by compression of root secondary to enlargement of cyst. All later specimens were found to be similarly atrophic.
5. D.&vis, B. K.: Quantitative morphological studies upon the influence of the endocrine system on the growth of hair by white mice. Acta Endocrinologica, 44: Supplement 85. Periodica, Copenhagen, 1963.
6. LOWENTHAL, L. A. ANO MONTAGNA, W.: Effects
of coloric restriction on skin and hair growth
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