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

THE CHEMISTRY OF ACNE VULGARIS 255 hypothalamus of the central nervous system. (To illustrate, before adoles- cence the central nervous system directs the pituitary to remain quiescent and not to produce sex gland stimulating hormones.) Once pituitary activity starts, it regulates the endocrine glands by a check and balance mechanism. The anterior portion of the pituitary gland puts forth so-called pituitary tropic hormones that stimulate the endocrine glands to secrete. The endocrine target glands in turn secrete characteristic hormones. If the target gland output is insufficient, {here is a compensatory increase in pituit- ary tropic hormones as a stimulant if target gland secretion is excessive, there is a compensatory decrease in pituitary tropic hormone as a depressor. The anterior lobe of the pituitary elaborates a series of hormones. The most significant ones for this thesis are (a) pituitary growth hormone (b) the adrenotropic hormones (c) the gonadotropic hormones, which maintain the activity of the sex glands--the ovaries and testes. In the female, the pituitary hormones are Follicle Stimulating Hormone (FSH), and Luteinising Hormone (LH). In the male, the hormone paralleling FSH influences the male gonad, and the luteiniser acts predominantly on the connective tissue derivatives-- i.e., the interstitial cells of the testes. Also, the anterior pituitary puts forth (d) a thyreotropic factor and (e) a lactogenic factor. Pituitary Growth Hormone (PGH) has a tremendous effect on the adoles- cent growth spurt. PGH is a protein, of molecular weight about 45,000 and of exact structure as yet undetermined. It acts directly on body structures rather than through a subsidiary endocrine gland. It has a profound relation to protein metabolism, and is a protoplasmic anabolic hormone--i.e., it causes body or tissue growth (anabolism), as opposed to utilising food by breakdown for energy (catabolism). Young animals whose pituitary glands have been removed show decreased growth that cannot be corrected by replacement with target gland extracts (--e.g., thyroid or a drenocortical hormones, or testosterone--which contributes to nitrogen or protein anabol- ism.) PGI-I promotes growth simply, and does not promote matmation. Probably, PGH has some relation to the pituitary sebaceous gland tropic factor that has been postulated•--since the sebaceous glands are body structures, not glands of internal secretion. PGH can cause increased serum alkaline phosphatase in experimental animals. •4 In man, tissue alkaline phosphatase is demonstrable in normal sweat glands and hair follicles, and also around the affected follicles in acne vulgaris. •5