THE CHEMISTRY OF ACNE VULGARIS 253 from the adrenal cortical hormones. Adrenosterone, the adrenal cortical androgen, is only very weakly androgeric, and only an abnormal variant of adrenosterone is secreted in adrenal virilising turnouts, where acne results. • 17-Hydroxy progesterone, an intermediary product in the metabolism of adrenal cortical hormones, has marked androgenic effects. a These evidences thus argue against androgens alone being etiologic in acne vulgaris. 3. It is customary to speak of an acheform eruption that follows the use of ACTH, cortisone and its derivatives. This acne is referred to as steroid acne and is a simple case of poor semantics. Estrogen, which is known to inhibit ache, is asteroid also, 'and has that same phenanthrene nucleus common to all steroids. A more apt name here would be ache due to adreno- tropic and adrenal cortical hormones. 4. Another fallacy is the assumption that the androgen/estrogen ratio must be out of balance in acne vulgaris, because estrogen is antagonistic to androgen and because estrogen inhibits acne. It is necessary to look further to see what other hormones are antagonistic in effect to estrogen. A new field then appears, where estrogen is antagonistic to pituitary growth hormone, to gonadotropic hormones of the anterior pituitary, and where estrogen has other effects, such as the ability to stimulate adrenotropic hormone production. • 5. Negative evidence must be weighed with care. For example, to say that an object is not green, does not mean that the object is blue. It could be violet, yellow, or red also. The effect of testosterone in producing acne has been supported by the observation that prepubertal castrates and eunuchoid males do not develop the skin condition. Other factors enter here. These abnormal individuals also do not develop beards, have altered body growth and hormone output, and do not present the usual emotional adaptation problems of adolescence. , 6. Lest it still is a temptation to ascribe acne entirely to hormonal aberrations, it should be noted that other mammalsmthat have hormone systems--nevertheless do not have ache. 4 When the current misconceptions are laid aside, then slightly more rigorous thinking may be indulged. To begin the development of a more rational theory, some fairly definite facts about sebaceous glands, adolescence and acne vulgaris must be reviewed. The sebaceous glands, which are the site of acne, empty into tke hair follicle, the whole being referred to as the pilosebaceous apparatus. Like other organs and systems, the sebaceous glands enlarge markedly in size during adolescence and the secretion of sebum has been found 'to be propmtionate to the gland surface. * How,ever, the sebum output fails to a stationary level between ages 20 to 25, 0 while the gland surface area remains the same. So another additional reason for the highly' accelerated

254 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS sebum secretion of the 'teens must exist. It is thought that ordinarily sebum is produced at a relatively constant rate. 7 The sebaceous gland empties into the hair follicle that is continuous with it. In acne, the hair follicle adjacent to the gland is filled with a horny plug--a hyperkeratotic or parakeratotic,scale.. Possibly, this may indicate pressure from the enlarged sebaceous gland on the contiguous epithelium, or it may be an independent process--perhaps of alteration of the hair follicle itself. Boys, at adolescence, develop beards--which could be a sufficient reason sui generis for the parakeratotic plug in the follicle. Anatomically, the epithelial wall of the hair follicle just adjoining the sebaceous gland has a clearl}f distinguished stratum granulosum during early acne only. 8 The stratum granulosum is a transitional layer between non-cornified and cornified (horny),epithelium. This layer contains micro- scopically visible keratohyalin granules, so called because they swell in alka- line solution--like hyalin. The granules are thought to represent proteins or protein decomposition products. 9 Consequently, the hair follicle plug in acne is a manifestation of a change in protein metabolism. The acne lesion has been observed to develop when the hair root in the involved follicle is in the telogen or resting phase of the hair growth cycle. 8 Interestingly enough, the resting phase of the hair cycle can be initiated or prolonged in mice by the administration of adrenal cortical steroids. TM The sebaceous glands themselves have no known nerve supply, but, rather, are suspected of being acted upon by endocrine secretions (the chemical output of the ductless glands). Since acne occurs in both boys and girls, it is obviously not entirely dependent on sex. A recognised observation is that there is a premenstrual aggravation of acne vulgaris, and this is ascribed by some to a decrease in estrogens (which inhibit acne) with resulting free play of the steroids of the adrenal cortex. Yet, the adrenal cortical steroids are secreted throughout a much longer part of life than puberty and the degree to which these hormones mimic testosterone is not clear, although evidence exists for the androgenic effect of an adrenat degradation product, 17-hydroxy progesterone. The existence of a clinical picture of acne after ACTH, cortisone or derivative therapy is established. n Here, a paradox must be mentioned. Cortisone is used in treating the disease adreno-cortical virilism. • But both cortisone and the condition, ad•eno- cortical virilism, can produce a clinical picture of acne. Thus, there must be a third factor, a common denominator that will explain why acne results from both instances. What else is definitely known ? A quick review of the endocrinology of adolescence related to' understanding acne is now in order. The pituitary gland, located next to the brain, is the master gland of the body. However, supreme control of endocrine secretion resides in the