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

256 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Estrogen can inhibit the growth promotion of PGH as well as inhibiting the gonadotropic secretion of the anterior pituitary. Estrogen also has the faculty of stimulating the output of adrenocorticotropic hormone (ACTH). ACTH is capable in turn of aggravating acne. Another estrogen effect is the hastening of skeletal maturation. Estrogen, used experimentally in ache therapy, can produce damage to the testicular tubules. The adrenocorticotropic hormones of the anterior pituitary elicit the adrenal cortical secretion of (1) DOCA, which regulates water metabolism, (2) the adrenal SFN hormones, which govern sugar, fat, and nitrogen metabolism--cortisone and corticosterone. The adrenal SFN hormones accelerate nitrogen catabolism, and so are antagonistic in effect to PGH. They have been demonstrated to have some bearing on the metabolism of compounds with SH groups--thus perhaps some bearing on skin meta- bolism. •6 Another adrenal cortical hormone is (3) adrenosterone, which may be a partial degradation product of the SFN hormones. The next area for consideration, and the particularly new aspect of the theory that is here presented, is the interplay between the sebaceous gland and the eccrine sweat gland. Because ache vulgaris is more severe in the tropics, where sweating is increased, the clinical effect of decreased sweating in patients with acne was assayed. •7 A complex form of aluminium hydroxychloride* was tested on skin in a 20 per cent aqueous solution. Thirty-three patients, treated for periods up to six monthsl between August 1954 and August 1956, showed accelerated initial clearing and easy maintenance of the end resultma less oily, acne-free skin. They were contrasted with 33 control patients. Laboratory investigators have observed that the rate of sebum spreading over a wet skin is of the order of at least 108 times the rate of flow and spread on a dry skin. •8 Conversely, variations in the level of ether-soluble substances (fats) in skin directly parallel the level of sweat delivery in the skin area. •9 Thus, an antiperspirant becomes a logical empirical sebaceous gland inhibitor. In the pathogenesis of acne, then, the substantial increase in sebum during puberty may be attributed to increased sweating. What are the causes of increased sweat production ? Normally, tempera- ture is an important conditioning factor. Hyperidrosis has two distinct mechanisms. One is an abnormal increase in nerve impulses to the sweat gland--such as may occur in central nervous system disorders and the other is emotional stimuli--such as fear, anger, etc. •ø Even straight mental problems--e.g., arithmetic---have been shown able to evoke sweat. The disturbance in all these cases produces the liberation of excessive amounts of acetylcholine, and subsequent excessive perspiration. * Astringen, supplied through the courtesy of Robinson, Wagner Co., New York City.