2000 ANNUAL SCIENTIFIC MEETING 147 helps maintain both epidermal and dermal health. Development of vitamin D analogs for pharmaceutical and cosmetic applications for skin health holds great promise. The skin produces the calciotropic hormone parathyroid hormone related peptide (PTHrP). Immunohistochemical localization of PTHrP in the epidermis revealed that there was a gradient of its expression with none being expressed in the basal cells and increased expression in the upper layers of the epidermis. PTHrP receptor agonists including PTH(1-34) and PTHrP(1-34) inhibit proliferation and induce terminal differentiation of cultured human keratinocytes and inhibit DNA synthesis in the epidermis of mice in vivo. A practical application for PTHrP agonists is for the treatment of hyperproliferative skin disorders. PTH(1-34) was formulated in a liposomal based cream and found to be effective when topically applied to patients with psoriasis. It was reasoned that if PTHrP is the endogenous factor that down regulates epidermal proliferation, that it might be possible to block its action by using a PTHrP receptor antagonist. It is known that PTH(7-34) binds to the receptor but does not cause any biologic function thereby acting as a pure antagonist. When PTH(7-34) was co-incubated with PTH(1-34) in cultured human keratinocytes, it partially restored the normal proliferative activity of the cells. When PTH(7-34), in a liposomal cream, was topically applied to SKH-1 hairless mice, it markedly enhanced DNA synthesis in a dose dependent fashion and increased the thickness of the epidermis two to three fold. No untoward toxicity was observed in the animals that received a topical application of this antagonist for two months.

148 JOURNAL OF COSMETIC SCIENCE The inner root sheath keratinocytes of the hair follicle also express PTHrP. It was reasoned that if PTHrP is the endogenous factor that down regulates proliferation, that it may be responsible for regulating the hair cycle. It was predicted that if PTH (7-34) could reverse the antiproliferative activity of PTHrP in the hair follicle, that it would stimulate and maintain hair growth. Studies were conducted in C57 BL/6 mice. The topical application of PTH(7-34) that was formulated in a liposomal cream to C57 BL/6 mice that had their hair follicles in telogen state stimulated them into anagen. It was also observed that PTH(7-34) helped preserve the hair follicles in their anagen VI phase. It was also reasoned, that if PTHrP is the factor that promotes the hair cycle into telogen, that it may be possible to use topical PTH(1-34)(the PTHrP agonist) as a mechanism to inhibit hair follicle progression from telogen into anagen. When PTH(1-34) was topically applied to C57 BL/6 mice in telogen, those animals that received placebo advanced into anagen II and III while the animals receiving topical PTH(1-34) remained in telogen. Thus, PTHrP agonists may be effective in preventing or reducing the appearance of unwanted hair. The skin is responsible for the production of two calciotropic hormones. It is now realized that these calciotropic hormones have direct actions on the skin. It is likely that of analogs of activated vitamin D, and agonist and antagonist analogs of PTHrP for skin and hair follicle growth will play an important role for the pharmaceutical and cosmetic industries in developing new skin health and skin care products for the new millennium. This work has been supported in part by NIH grants R01 AR 36963, M01RR 00533, DK50102, CA71119, and Holtherics, Inc.