Hair growth
Hair growth-modulation by adrenergic drugs.

Peters EM, Maurer M, Botchkarev VA, Gordon DS, Paus R.

Department of Dermatology, Charite, Humboldt-Universitat zu Berlin, Germany.

Since we have recently shown that the beta 2-adrenoreceptor (beta 2-AR) expression of selected regions of the hair follicle (HF) epithelium as well as the number of adrenergic nerve fibers in murine skin change in a hair cycle-dependent manner, this has raised the possibility that adrenergic nerves may exert "trophic" functions during HF cycling. To further explore this concept, we have investigated the effect of neuro-pharmacological manipulations on hair growth (anagen) induction in quiescent telogen mouse skin in vivo. Here, we demonstrate that subcutaneous injections of the noradrenaline (NA)-depleting agent guanethidine, or of the neurotoxin 6-hydroxydopamine, but not of the beta 2-AR agonist isoproterenol induce a premature onset of anagen in the lower back skin of C57BL/6 mice. On day 20 after the start of treatment, more than 80% of the guanethidine-treated mice and ca. 65% of the 6-hydroxydopamine-treated (6-OHDA) mice exhibited premature skin darkening and hair growth at the site of drug application, whereas less than one-third of all control animals showed macroscopic signs of anagen development. This was confirmed by histology, demonstrating mature anagen VI HFs only at the immediate site of treatment with guanethidine or 6-OHDA as opposed to resting telogen HFs in the neighboring untreated skin area. This observation further supports the concept that sympathetic nerves are intimately involved in hair growth control and invites one to explore the neuro-pharmacological manipulation of piloneural interactions as a novel therapeutic strategy for the management of hair growth disorders.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10439225&dopt=Abstract alopecia, hair loss hair growth



Hair growth
The mRNA for protease nexin-1 is expressed in human dermal papilla cells and its level is affected by androgen.

Sonoda T, Asada Y, Kurata S, Takayasu S.

Department of Dermatology, Oita Medical University, Hasama, Japan. sonodat oita-med.ac.jp

Protease nexin-1, an inhibitor of serine proteases, plays important parts in the regulation of the growth, differentiation, and death of cells by modulating proteolytic activity. The mRNA for protease nexin-1 accumulates in rat dermal papilla cells in a hair cycle-dependent fashion and its levels are well correlated with the ability of dermal papilla cells to support hair growth. In an attempt to characterize the potential role of protease nexin-1 as a modulator of hair growth in humans, we investigated the steady-state level of protease nexin-1 mRNA in cultured human dermal papilla cells using a semiquantitative technique that involved reverse transcription and polymerase chain reaction, as well as the localization of this mRNA in vivo using dissected hair follicles. Protease nexin-1 mRNA was expressed in all dermal papilla cells examined, and it was also identified in the lower part of the connective tissue sheath. Moreover, we found that levels of protease nexin-1 mRNA were depressed by dihydrotestosterone, the most potent androgen, in cultured dermal papilla cells obtained from balding scalp. Our results suggest that protease nexin-1 might be a key molecule in the control of hair growth in humans and, moreover, that the androgen-mediated downregulation of the synthesis of protease nexin-1 might be associated with the progression of male-pattern baldness.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10469326&dopt=Abstract alopecia, hair loss hair growth



Hair growth
Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog.

Sato N, Leopold PL, Crystal RG.

Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University-New York Presbyterian Hospital, New York, New York 10021, USA.

Hair follicles form in prenatal skin and mature in the postnatal period, establishing a growth cycle in 3 phases: telogen (resting), anagen (growth), and catagen (regression). Based on the knowledge that Sonic hedgehog (Shh) expression is necessary for the embryonic development of hair follicles, and that anagen in the postnatal cycling follicle has morphologic similarities to the epithelial invagination process in embryonic skin, we hypothesized that localized, but transient, enhanced expression of the Shh gene in postnatal skin would accelerate initiation of anagen in the hair follicle cycle, with concomitant accelerated hair growth. To assess this concept, an E1(-) adenovirus vector, AdShh, was used to transfer the murine Shh cDNA to skin of postnatal day 19 C57BL/6 mice. The treated skin showed increased mRNA expression of Shh, Patched (the Shh receptor), and Gli1 (a transcription factor in the Shh pathway). In mice receiving AdShh, but not in controls, acceleration into anagen was evident, since hair follicle size and melanogenesis increased and the hair-specific keratin ghHb-1 and the melanin synthesis-related tyrosinase mRNAs accumulated. Finally, C57BL/6 mice showed marked acceleration of the onset of new hair growth in the region of AdShh administration to skin 2 weeks after treatment, but not in control vector-treated or untreated areas. After 6 months, AdShh-treated skin showed normal hair and normal skin morphology. Together, these observations are consistent with the concept that upregulation of Shh activity in postnatal skin functions as a biologic switch that induces resting hair follicles to enter anagen with consequent hair growth.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10510326&dopt=Abstract alopecia, hair loss hair growth



Hair growth
Computerized assessment of facial hair growth.

Gruber DM, Berger UE, Sator MO, Horak F, Huber JC.

Department of Gynecological Endocrinology and Reproductive Medicine, Clinic for Gynecology and Obstetrics, University of Vienna Medical School, General Hospital (Allgemeines Krankenhaus), Austria. doris.gruber akh-wien.ac.at

OBJECTIVE: To evaluate a computer-assisted technique for objective and sensitive monitoring of facial hair growth. DESIGN: Prospective study. SETTING: Department of Gynecological Endocrinology and Reproductive Medicine and Clinic for Ear, Nose, and Throat, General Hospital, University of Vienna, Vienna, Austria. PATIENT(S): Four men, three hirsute women, and three nonhirsute women. INTERVENTION(S): Using video equipment and computer software, we were able to document, analyze, and store data regarding hair growth in specific areas of interest. For digital image analysis, we used the Digi Trace System (Olympus, Vienna, Austria; Imatec, Munich, Germany). MAIN OUTCOME MEASURE(S): Hair growth within 20 days in well-defined regions of interest on the faces of hirsute and nonhirsute women and of men. RESULT(S): Hair growth on day 21 was significantly different between hirsute and nonhirsute women as well as in men. The scores for individual hair growth between day 0 and day 21 also were significantly different in hirsute women and in men. No statistically significant difference in hair growth was found within the group of nonhirsute women. CONCLUSION(S): With digital image analysis, facial hair growth, especially in hirsute women, can be calculated in a sensitive and objective manner.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10521121&dopt=Abstract alopecia, hair loss hair growth



Hair growth
Cyclopentyladenosine improves cell proliferation, wound healing, and hair growth.

Sun LL, Xu LL, Nielsen TB, Rhee P, Burris D.

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20852, USA. lsun usuhs.mil

BACKGROUND: N(6)-Cyclopentyladenosine (CPA), a structural analog of adenosine, is a vasodilator with extensive pharmacological effects. However, little is known about the effect of CPA on wound healing and hair growth. METHODS: Cellular responses to CPA were measured in vitro by tetrazolium dye reduction and in vivo by bromodeoxyuridine (BrdU) uptake. The effect of CPA on healing of incisional and excisional wounds on the dorsum of diabetic (db/db, n = 94) and nondiabetic (db/+, n = 20) mice and hair growth along the wound margin was evaluated with wound breaking strength, wound closure rate, and quantitative histology. RESULTS: CPA stimulated proliferation of BALB/3T3 fibroblasts and human dermal microvascular endothelial cells in both quiescent and nonquiescent phases. Wounds treated with CPA at 10 microM showed a significant increase in the number of BrdU-labeled cells, including keratinocytes, fibroblasts, endothelial cells, and cells in sebaceous glands and the outer root sheath of hair follicles, compared with controls (P < 0.05). CPA application (5.1 microg/daily for 12 days) significantly increased the breaking strength of incisional wounds at day 24 postwound (P < 0.05). Excisional wound closure rate in the CPA-treated group (3.4 microg/daily for 15 days) was accelerated starting at day 10 postwound compared with controls (P < 0.01). Tissue sections from CPA-treated wounds showed a sevenfold increase in hair follicle number, compared with controls (P < 0.01). Enhanced hair growth along the wound margin was revealed in CPA-treated groups. CONCLUSION: CPA stimulated proliferation of many cell types in vivo and in vitro and enhanced wound healing and hair growth. Therefore, CPA could be an interesting candidate for clinical application. Copyright 1999 Academic Press.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10527699&dopt=Abstract alopecia, hair loss hair growth



Hair growth
Hair cycle-dependent changes in adrenergic skin innervation, and hair growth modulation by adrenergic drugs.

Botchkarev VA, Peters EM, Botchkareva NV, Maurer M, Paus R.

Department of Dermatology, Charite, Humboldt University, Berlin, Germany.

Skin nerves may exert "trophic" functions during hair follicle development, growth, and/or cycling. Here, we demonstrate hair cycle-related plasticity in the sympathetic innervation of skin and hair follicle in C57BL/6 mice. Compared with telogen skin, the number of nerve fibers containing norepinephrine or immunoreactive for tyrosine hydroxylase increased during the early growth phase of the hair cycle (anagen) in dermis and subcutis. The number of these fibers declined again during late anagen. beta2-adrenoreceptor-positive keratinocytes were transiently detectable in the noncycling hair follicle epithelium, especially in the isthmus and bulge region, but only during early anagen. In early anagen skin organ culture, the beta2-adrenoreceptor agonist isoproterenol promoted hair cycle progression from anagen III to anagen IV. The observed hair cycle-dependent changes in adrenergic skin innervation on the one hand, and hair growth modulation by isoproterenol, accompanied by changes in beta2-adrenoreceptor expression of selected regions of the hair follicle epithelium on the other, further support the concept that bi-directional interactions between the hair follicle and its innervation play a part in hair growth control. This invites one to systematically explore the neuropharmacologic manipulation of follicular neuroepithelial interactions as a novel therapeutic strategy for managing hair growth disorders.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10594725&dopt=Abstract alopecia, hair loss hair growth