Identification and selective inhibition of an isozyme of steroid 5 alpha-reductase in human scalp.
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Steroid 5 alpha-reductase (EC 1.3.1.22) catalyzes the reduction of testosterone to dihydrotestosterone. The 5 alpha-reductase found in human scalp has been compared with the enzyme found in prostate. The scalp reductase has a broad pH optimum centered at pH 7.0. This is distinctly different from the pH optimum of 5.5 observed with the prostatic form of the enzyme. These enzymes also differ in the Km for testosterone, which is 25-fold higher for the scalp reductase. The most significant difference between the two enzymes is their affinity for inhibitors. Two 4-azasteroids and a 3-carboxyandrostadiene are potent inhibitors of the prostatic reductase but are weak inhibitors of the scalp reductase. In contrast, several N-4-methylazasteroids are good inhibitors of the scalp reductase. These findings support a proposal that different isozymes of 5 alpha-reductase may exist in scalp and prostate. The scalp reductase was also compared to 5 alpha-reductase 1, one of the two enzymes recently cloned from human prostate [Andersson, S. & Russell, D. W. (1990) Proc. Natl. Acad. Sci. USA 87, 3640-3644; and Andersson, S., Berman, D. M., Jenkins, E. P. & Russell, D. W. (1991) Nature (London) 354, 159-161]. The characteristics of the cloned reductase 1 are comparable to those of the scalp reductase. (+info)
The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals.
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The aim of the present study was to determine the expression of the genes for type 1 (SDR5A1) and type 2 (SDR5A2) 5alpha-reductase isoenzymes in scalp hairs plucked from 33 hirsute patients (20 with polycystic ovary syndrome and 13 with idiopathic hirsutism) and compare it with that of 10 men and 15 normal women. SDR5A1 and SDR5A2 expression was estimated by RT-PCR using the gene of the ubiquitously expressed protein 2-microglobulin as an internal control. The results are expressed as arbitrary units in relation to beta2-microglobulin absorbance (mean SEM). SDR5A2 expression was not detected in any hair samples analyzed in this study. No differences were found in SDR5A1 mRNA levels between men and normal women (0.78+/-0.05 vs 0.74+/-0.06, respectively). SDR5A1 gene expression in the cells of hair plucked from the scalp of normal women (0.85+/-0.04) and of women with polycystic ovary syndrome (0.78+/-0.05) and idiopathic hirsutism (0.80+/-0.06) was also similar. These results indicate that SDR5A1 gene expression in the follicular keratinocytes from the vertex area of the scalp seems not to be related to the differences in hair growth observed between normal men and women and hirsute patients. Further studies are needed to investigate the expression of the 5alpha-reductase genes in other scalp follicular compartments such as dermal papillae, and also in hair follicles from other body sites, in order to elucidate the mechanism of androgen action on the hair growth process and related diseases. (+info)
Human handedness and scalp hair-whorl direction develop from a common genetic mechanism.
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Theories concerning the cause of right- or left-hand preference in humans vary from purely learned behavior, to solely genetics, to a combination of the two mechanisms. The cause of handedness and its relation to the biologically specified scalp hair-whorl rotation is determined here. The general public, consisting of mostly right-handers (RH), shows counterclockwise whorl rotation infrequently in 8.4% of individuals. Interestingly, non-right-handers (NRH, i.e., left-handers and ambidextrous) display a random mixture of clockwise and counterclockwise swirling patterns. Confirming this finding, in another independent sample of individuals chosen because of their counterclockwise rotation, one-half of them are NRH. These findings of coupling in RH and uncoupling in NRH unequivocally establish that these traits develop from a common genetic mechanism. Another result concerning handedness of the progeny of discordant monozygotic twins suggests that lefties are one gene apart from righties. Together, these results suggest (1) that a single gene controls handedness, whorl orientation, and twin concordance and discordance and (2) that neuronal and visceral (internal organs) forms of bilateral asymmetry are coded by separate sets of genetic pathways. The sociological impact of the study is discussed. (+info)
Cutaneous angiosarcoma of the scalp: a multidisciplinary approach.
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BACKGROUND: Angiosarcoma is a malignant tumor of vascular endothelial cells that arises in the head and neck. It is a rare, difficult to treat, and lethal tumor. METHODS: Clinical data from patients who were diagnosed with angiosarcoma of the scalp between 1975 and 2002 at the University of Michigan were reviewed. Analysis was performed to assess for factors impacting time to recurrence and survival. RESULTS: The study was comprised of 29 patients with a median age of 71.0 years. Most patients presented after a delay in diagnosis with either a bruise-like macule (48.3%) or a nonbruise-like nodule (51.7%). Seventy-five percent of patients had pathologic Stage T2 disease, and 76% of patients had high-grade tumors. Virtually all patients underwent surgical excision (96.6%); however, negative surgical margins were achieved in only 21.4% of patients. Multiple lesions on presentation were associated with a shorter time to recurrence (P = 0.02). The median actuarial survival was 28.4 months. Younger patients and patients with Stage T1 disease had improved survival (P = 0.024 and P = 0.013, respectively). Radiation therapy was associated significantly with a decreased chance of death (hazard ratio, 0.16; P = 0.006). CONCLUSIONS: Although surgery remains the first option for the treatment of patients with angiosarcoma of the scalp, achieving negative margins often is impossible. Patients who are younger and who have less extensive disease fare better. Postoperative radiation therapy should be employed routinely, as it may lead to improved survival. (+info)
Differential expression of a cutaneous corticotropin-releasing hormone system.
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We completed the mapping of a cutaneous CRH signaling system in two species with widely different determinants of skin functions, humans and mice. In human skin, the CRH receptor (CRH-R) 1 was expressed in all major cellular populations of epidermis, dermis, and subcutis with CRH-R1alpha being the most prevalent isoform. The CRH-R2 gene was expressed solely in hair follicle keratinocytes and papilla fibroblasts, whereas CRH-R2 antigen was localized predominantly in hair follicles, sebaceous and eccrine glands, muscle and blood vessels. In mouse skin, the CRH-R2 gene and protein were widely expressed in all cutaneous compartments and in cultured normal and malignant melanocytes. CRH-binding protein mRNA was present in dermal fibroblasts, melanoma cells, and sc fat of human skin and undetectable in mouse skin. The urocortin II gene was expressed equally in mouse and human skin. Taken together with our previous investigations, the present studies document the preferential expression of CRH-R1 in human skin, which mirrors CRH-R2 expression patterns in human and mouse skin. They are likely reflecting different functional activities of human and mouse skin. The adnexal location of CRH-R2 suggests a role for the receptor in hair growth. The differential interspecies CRH signaling expression pattern probably reflects adaptation to species-specific skin function determinants. (+info)
Distant metastasis of dermatofibrosarcoma protuberans of the scalp--case report.
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A 49-year-old man presented with a rare dermatofibrosarcoma protuberans (DFSP) of the scalp associated with local recurrence and distant metastasis to the lung and abdomen. An elastic-hard small mass on the right occipital scalp was initially treated by simple resection in another clinic. Ten years later, recurrent tumor was associated with infiltration to the calvarium, and resection was performed again also in another clinic. Approximately 1.5 years later, the patient was transferred to our clinic because of recurrence with intracranial involvement. Repeated relapses and metastasis to the lung were recognized despite surgery, chemotherapy, and local radiation. Eventually, the patient died of distant metastasis to the abdomen 17 years after the initial diagnosis. Scalp DFSP is very uncommon but is an aggressive scalp tumor, so initial wide local resection and local radiation therapy after surgery are important to prevent local recurrence and distant metastasis. (+info)
A survey on health effects in a human population exposed to permanent-waving solution containing thioglycolic acid.
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Thioglycolic acid (TGA) is the active ingredient of permanent-waving solution (PWS). TGA has been shown to be a chemical of high toxicity, which can be absorbed through intact skin and cause damage to organs or systems in animals. This study evaluated the effect of TGA-containing PWS on the health of a human population in 3 substudies. Firstly, 57 female hairdressers exposed to TGA-containing PWS (cases) and 64 female schoolteachers (controls) were studied. Their menstruation state was evaluated with information obtained from interviews. The results revealed that the menoxenia rate in the cases was significantly higher than that in the controls (22.81% vs 9.38%, p<0.05). Secondly, 8 female hairdressers selected from those that participated in the above survey underwent a fluctuation test for the mutagenic activity of urine. Eight female medical students were chosen as controls. Difference in the mutagenic activity of urine on TA100 between the two groups was highly significant (110.30 +/- 45.95 vs 28.43 +/- 19.33, p<0.01). Finally, a micronucleus assay was carried out on scalp hair follicle cells in healthy volunteers. Scalp hair with the follicle cell mass was sampled from 8 male and 8 female volunteers before permanent waving and at 24, 48 and 72 h after waving. One thousand hair follicle cells were examined by light microscopy. The number of cells containing a micronucleus and the number of micronuclei in each cell was determined. The permillages of micronuclei in hair follicle cells before and after permanent waving were compared. Micronuclei presence reached its peak value (12.44) 24 h after permanent waving, which was significantly higher than that before waving (3.13, p<0.001). The rate decreased progressively after 24 h. Our results suggest that the reproductive function of hairdressers may be affected by long-term exposure to PWS, probably due to the presence of TGA, and more attention should be paid to its potential carcinogenic effects. (+info)
Role of primary sensorimotor cortex and supplementary motor area in volitional swallowing: a movement-related cortical potential study.
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We investigated the role of the cerebral cortex, particularly the face/tongue area of the primary sensorimotor (SMI) cortex (face/tongue) and supplementary motor area (SMA), in volitional swallowing by recording movement-related cortical potentials (MRCPs). MRCPs with swallowing and tongue protrusion were recorded from scalp electrodes in eight normal right-handed subjects and from implanted subdural electrodes in six epilepsy patients. The experiment by scalp EEG in normal subjects revealed that premovement Bereitschaftspotentials (BP) activity for swallowing was largest at the vertex and lateralized to either hemisphere in the central area. The experiment by epicortical EEG in patients confirmed that face/tongue SMI and SMA were commonly involved in swallowing and tongue protrusion with overlapping distribution and interindividual variability. BP amplitude showed no difference between swallowing and tongue movements, either at face/tongue SMI or at SMA, whereas postmovement potential (PMP) was significantly larger in tongue protrusion than in swallowing only at face/tongue SMI. BP occurred earlier in swallowing than in tongue protrusion. Comparison between face/tongue SMI and SMA did not show any difference with regard to BP and PMP amplitude or BP onset time in either task. The preparatory role of the cerebral cortex in swallowing was similar to that in tongue movement, except for earlier activation in swallowing. Postmovement processing of swallowing was lesser than that of tongue movement in face/tongue SMI; probably suggesting that the cerebral cortex does not play a significant role in postmovement processing of swallowing. SMA plays a supplementary role to face/tongue SMI both in swallowing and tongue movements. (+info)