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During the past decade we have examined both the therapeutic and the prophylactic effects of several agents on the macaque model of androgenetic alopecia. Minoxidil and diazoxide, potent hypotensive agents acting as peripheral vasodilators, are known to have a hypertrichotic side effect. Topical use of both agents induced significant hair regrowth in the bald scalps of macaques. The application of a steroid 5 alpha-reductase inhibitor (4MA) in non-bald preadolescent macaques has prevented baldness, whereas controls developed it during 2 years of treatment. The effects of hair growth were determined by 1) phototrichogram, 2) folliculogram (micro-morphometric analysis), and 3) the rate of DNA synthesis in the follicular cells. These effects were essentially a stimulation of the follicular cell proliferation, resulting in an enlargement of the anagen follicles from vellus to terminal type (therapy) or a maintenance of the prebald terminal follicles (prevention). A copper binding peptide (PC1031) had the effect of follicular enlargement on the back skin of fuzzy rats, covering the vellus follicles; the effect was similar to that of topical minoxidil. Analyzing the quantitative sequences of follicular size and cyclic phases, we speculate on the effect of agents on follicular growth. We also discuss the triggering mechanism of androgen in the follicular epithelial-mesenchymal (dermal papilla) interaction.

Plugs of occipital hairy scalp and pieces of digital pads were transplanted to the frontal scalp of stump-tailed macaques (Macaca arctoides). Both types of grafts grew well and retained their original appearance for several years. We traced the regrowth and reinnervation of hair follicles and Meissner corpuscles in sequential biopsy specimens of these grafts. Two weeks after transplantation, hair follicles in the grafts appeared to have lost all integrity but began to regrow after 4 weeks. The nerve and organs of hair follicles began to reappear at 8 weeks. Thereafter, grafts with large terminal hairs remained viable in the host bald frontal scalp for as long as 8 yr. In the digital skin grafts, the cytoskeleton of the Meissner corpuscles could be distinguished after 4 weeks; after 8 weeks nerves from the host tissue could be traced to the end organs. Perivascular nerve plexuses and nerves to the piloerector muscles were clearly seen in both types of graft after 8 weeks.

Substance P is an undecapeptide found in multiple sites throughout the central and peripheral nervous systems including small unmyelinated (type C) cutaneous nerve fibers. Previous studies demonstrated that antidromic stimulation results in substance P (SP) release from nerve endings, SP stimulates histamine release (HR) from rat mast cells in vitro, and intradermal SP in humans produces wheals identical to those induced by histamine. These studies suggest a possible role for SP as a link between neurologic events and cutaneous mast cell-mediated reactions. We therefore investigated SP-induced HR in an in vitro preparation of human skin mast cells. Human foreskin sections were incubated with varying concentrations of SP. Histamine was assayed using automated fluorimetry and release was calculated as a percentage of total tissue histamine. Substance P caused dose-dependent HR over a range from 10(-5) M (1.3%) to 5 X 10(-4) M (25.1%). Histamine release was optimal at 3 mM calcium and was blocked by pretreatment with calcium chelation. Naloxone failed to block HR. These studies suggest that HR from skin mast cells by SP may play a role in neural modulation of poorly understood inflammatory skin conditions.