References: Hair growth and hair loss
J Invest Dermatol. 1997 Jun;108(6):864-70.
Keratinocyte K+ channels mediate Ca2+-induced differentiation.
Mauro T, Dixon DB, Komuves L, Hanley K, Pappone PA.
Department of Dermatology, University of CA, San Francisco, California, USA.
K+ channel activation has been associated with growth or differentiation in many cells. We have previously identified a 70-pS K+ channel that was found only in differentiated involucrin-positive cells. In this study we examined the role of K+ channels in Ca2+-induced keratinocyte differentiation. Consistent with our previous report, we found that a K+ conductance developed only in cells cultured in high extracellular Ca2+. Addition of charybdotoxin or verapamil blocked these K+ channels and inhibited Ca2+-induced differentiation, as assessed by cornified envelope formation or transglutaminase activity. These results suggest that K+ channel activation is necessary for Ca2+-induced differentiation. Finally, we used (125)I-labeled charybdotoxin to demonstrate the presence of K+ channels in intact human and mouse epidermis, hair follicles, and eccrine glands, indicating that these channels are found in keratinocytes both in vitro and in vivo. Thus K+ channels may moderate Ca2+ influx in more differentiated keratinocytes and may play a central role in keratinocyte differentiation.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9182812&dopt=Abstract
J Invest Dermatol. 1997 Jun;108(6):928-32.
Control of hair growth with parathyroid hormone (7-34).
Schilli MB, Ray S, Paus R, Obi-Tabot E, Holick MF.
Department of Medicine, Boston University Medical Center, Massachusetts 02118, USA.
Parathyroid hormone (PTH) related peptide (PTHrP) is thought to influence the proliferation and differentiation of the epidermis and hair follicle. As a means of elucidating the biologic function of PTHrP on the hair follicle, a PTHrP analog PTH (7-34), which is a PTH/PTHrP receptor antagonist, was given intraperitoneally twice daily to C57 BL/6 mice at different stages of the hair cycle. PTH (7-34) induced 99 +/- 4.5% (mean +/- SEM) of resting telogen hair follicles into a proliferative (anagen) state, whereas 100% of the hair follicles in the control group remained in telogen. To determine whether this peptide influenced the progression of the hair follicles from anagen to catagen (hair follicle maturation and regression), groups of mice that were either spontaneously in or induced to anagen received either PTH (7-34) or placebo. Morphometric analysis of the hair follicles from the middle back region of the spontaneous anagen mice that received PTH (7-34) revealed that 19 +/- 4% (mean +/- SEM) of the follicles were in anagen VI, whereas none (0%) were in anagen in the control group. Similarly, in induced anagen mice treated with PTH (7-34), 22.3 +/- 1.4 (mean +/- SEM) of the follicles were in anagen VI compared to only 1.3 +/- 0.7% in the control mice. Together these observations suggest that PTHrP is a hair follicle morphogen that may be a major factor responsible for controlling the hair cycle. These studies provide a new insight for development of PTHrP analogs for a wide variety of disorders related to disturbances of hair cycling.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9182824&dopt=Abstract
Exp Neurol. 1997 May;145(1):104-17.
Intracerebroventricular glial cell line-derived neurotrophic factor improves motor function and supports nigrostriatal dopamine neurons in bilaterally 6-hydroxydopamine lesioned rats.
Bowenkamp KE, Lapchak PA, Hoffer BJ, Miller PJ, Bickford PC.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
In order to evaluate the efficacy of glial cell line-derived neurotrophic factor (GDNF) in a model of advanced Parkinson's disease, we studied rats with extensive bilateral lesions of the nigrostriatal pathway. Adult male F344 rats were injected bilaterally into the medial forebrain bundle with the neurotoxin 6-hydroxydopamine. Locomotor ability as measured by total distance traveled in an open field over 20 min, as well as von Frey hair testing of sensorimotor neglect, was monitored weekly. Rats demonstrating severe motor impairment and sensorimotor neglect were used for this study and were sorted to achieve similar average behavioral scores between the two treatment groups. After 2 weeks of pretesting, the rats received 250 microg GDNF or vehicle injected into the right lateral cerebral ventricle. Three weeks later, an additional 500 microg GDNF or vehicle was injected into the contralateral ventricle. The rats were monitored for another 2 weeks prior to sacrifice. Behavioral results indicated that von Frey hair scores were inconsistent between tests for each rat and were unchanged following GDNF treatment. However, GDNF recipients demonstrated significant improvement in locomotor ability compared to vehicle recipients. High-pressure liquid chromatography-electrochemical detection analysis of neurotransmitter levels revealed a significant increase in dopamine content within the substantia nigra and ventral tegmenta, but not the striata, of GDNF-treated rats. Further, immunohistochemical staining of tissues from matched pairs of rats revealed increased numbers of tyrosine hydroxylase-positive ventral mesencephalic neurons in one of the two pairs of rats examined. These results suggest that intracerebroventricular GDNF administration improves motor ability and supports nigrostriatal dopaminergic neurons in a model of severe Parkinson's disease.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9184114&dopt=Abstract
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