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1.
Nuclear hormone receptors are of critical importance for skin homeostasis where they modulate cellular metabolism, proliferation, differentiation, cell death, and inflammation. The cutaneous role of the glucocorticoid, androgen, and estrogen receptors was explored initially. In recent years, sequence homology comparisons have uncovered the complete superfamily of related receptors, many of which are also implicated in cutaneous homeostasis. A subgroup of these receptors acts in concert with the retinoid X receptor by heterodimerization and has been successfully targeted for dermatologic therapy; i.e., the retinoic acid receptor and the vitamin D receptor. Ongoing research is aimed at delineating the cutaneous effects of additional members of this subgroup including the peroxisome proliferator-activated receptors and the liver X receptors. The various receptors exert differential effects in skin and can be rationally chosen as drug targets for the treatment of cutaneous pathologies.  相似文献   

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Localization of sex steroid receptors in human skin   总被引:10,自引:0,他引:10  
Sex steroid hormones are involved in regulation of skin development and functions as well as in some skin pathological events. To determine the sites of action of estrogens, androgens and progestins, studies have been performed during the recent years to accurately localize receptors for each steroid hormone in human skin. Androgen receptors (AR) have been localized in most keratinocytes in epidermis. In the dermis, AR was detected in about 10% of fibroblasts. In sebaceous glands, AR was observed in both basal cells and sebocytes. In hair follicles, AR expression was restricted to dermal papillar cells. In eccrine sweat glands, only few secretory cells were observed to express AR. Estrogen receptor (ER) alpha was poorly expressing, being restricted to sebocytes. In contrast, ERbeta was found to be highly expressed in the epidermis, sebaceous glands (basal cells and sebocytes) and eccrine sweat glands. In the hair follicle, ERbeta is widely expressed with strong nuclear staining in dermal papilla cells, inner sheath cells, matrix cells and outer sheath cells including the buldge region. Progesterone receptors (PR) staining was found in nuclei of some keratinocytes and in nuclei of basal cells and sebocytes in sebaceous glands. PR nuclear staining was also observed in dermal papilla cells of hair follicles and in eccrine sweat glands. This information on the differential localization of sex steroid receptors in human skin should be of great help for future investigation on the specific role of each steroid on skin and its appendages.  相似文献   

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Toll-like receptors and their role in animal reproduction   总被引:1,自引:0,他引:1  
Toll-like receptors (TLRs) are evolutionarily conserved innate immune receptors that recognize pathogen specific molecular pattern (PAMPs) in an efficient, non-self-reactive manner and initiate specific immune signaling that culminates in triggering antigen-specific adaptive responses. Different TLR genes in domestic animal species have been characterized and accumulating evidence from recent studies indicates an extended role for TLR signaling in reproductive physiology. In females, TLRs have been implicated in the regulation of ovulation, fertilization, gestation and parturition, as well as in pathological conditions such as endometritis and mastitis. In males, TLRs play a role in steroidogenesis and spermatogenesis. Use of TLR agonists has also been shown to be effective in the treatment of certain reproductive tract infections. Moreover, gene polymorphisms in TLRs have been associated with mastitis providing evidence that TLRs can potentially be exploited as markers in future breeding programs. The aim of this review is to provide a comprehensive treatise on role of TLRs in male and female reproductive physiology and associated pathology in domestic livestock.  相似文献   

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Using confocal laser scanning microscopy, we tested the suitability of five monoclonal mouse antibodies (IVA7E7, IVB12G12, IVG9C11, VD2F12, and VIIID8C12) that had been raised against different domains of the porcine intestinal 1,25-dihydroxyvitamin-D3 receptor (VDR), for the immunohistological detection of VDR in human skin. The VDR immunoreactivity of these antibodies was compared with the well-characterized VDR-staining pattern of the mouse monoclonal antibody 9A7 raised against chick intestinal VDR. All six antibodies revealed strong nuclear and qualitatively similar immunoreactivity in all cell layers of the viable epidermis. Our data demonstrate that the five mouse monoclonal antibodies are suitable for immunohistochemical detection of VDR in frozen sections. These antibodies show comparable staining patterns in human skin even though they had been raised against different functional domains of the 1,25-dihydroxyvitamin-D3 receptor.  相似文献   

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A method is described for the determination of binding capacity (Ro) and dissociation constant (Kd) of androgen receptors in dispersed, whole, cultured human skin fibroblasts. The cells, obtained from punch biopsies or operative specimens of skin, are grown to confluence in monolayers, harvested, washed, and dispersed in medium. Binding is assessed by incubating the cells with [3H]dihydrotestosterone3 (DHT) at 22°C for one hour followed by washing, centrifugation and counting. Non-specific binding is determined by adding radioinert methyltrienolone (R1881). Scatchard plots are constructed using 6 concentration points; binding is expressed as sites/cell. The method is precise (Ro = 12,105 ± 4305 (S.D.) sites/cell; Kd = 1.0 ± 0.7 (S.D.) × 10?9M, n = 14 for one prepuce cell line) and independent of cell passage number. Binding is linear with respect to cell number and shows those characteristics commonly attributed to androgen receptors: high affinity, low binding capacity, saturable nuclear binding, androgen specificity, and an 8S peak in fibroblast cytosol using sucrose density gradients. Cell lines shown by other published methods to lack androgen receptors had no detectable DHT binding with this method. This assay technique has the advantages of simplicity, rapidity, and precision.  相似文献   

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PPARs are nuclear hormone receptors. PPAR subtypes (alpha, gamma, delta, the latter a xPPARbeta homologue) were initially investigated in skin because of their known role in regulating lipid metabolism. Studies adding specific PPAR ligand activators to cultured skin or skin cells are compatible with the concepts that PPARalpha activation mediates early lipogenic steps common to the function of both skin epidermal cells (keratinocytes) and sebaceous cells (sebocytes), PPARgamma activation plays a unique role in stimulating sebocyte lipogenesis, and PPARdelta activation may contribute to lipid biosynthesis in both sebocytes and keratinocytes under certain circumstances. Epidermal keratinocytes appear to express small amounts of PPARalpha and PPARdelta mRNA and a trace of PPARgamma mRNA which is up-regulated with differentiation. Sebocytes express all subtypes; PPARgamma gene expression excedes that in epidermis. The emerging data on PPAR protein expression suggests that epidermis normally expresses predominantly PPARalpha, while sebocytes express more PPARgamma than PPARalpha. These expression patterns may change during hyperplasia, differentiation and inflammation. Gene disruption studies in mice are compatible with a contribution of PPARalpha to skin barrier function, suggest that PPARgamma is necessary for sebocyte differentiation, and indicate that PPARdelta can ameliorate inflammatory responses in skin. PPARs appear to play a role in keratinocyte synthesis of the lipids that they export to the intercellular space to form the skin permeability barrier. They also appear to be important for sebocyte formation of the intracellular fused lipid droplets that constitute the holocrine secretion of the sebaceous gland. In addition, they may play roles in keratinocyte growth and differentiation and the inhibition of skin inflammation by diverse mechanisms not necessarily related to fat metabolism.  相似文献   

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During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabeled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of kinin-B1 receptors did not appear to be enhanced in the other biopsies. Within the multiple steps of the inflammatory cascade in wound healing, our results suggest an important regulatory role for kinin-B1 receptors during the first phase of inflammation following injury.  相似文献   

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The examples shown here illustrate the power of gene targeting to the epidermis as a means of developing animal models for the study of human skin diseases. In this short review, I have focused on contributions which stem predominantly from my own laboratory [31, 32, 34, 37, 47]. However, other laboratories have also contributed heavily to the development of this technology [28-30, 35, 36]. The opportunities for these models are vast: there are a myriad of human skin diseases which have been characterized extensively at a biological level, but whose aetiology is presently unknown. A combined knowledge of (a) the biochemistry of epidermal differentiation; (b) epidermal-specific gene expression; and (c) transgenic mouse technology has provided the foundation for these and future studies in this area.  相似文献   

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Boron in human and animal nutrition   总被引:9,自引:0,他引:9  
Nielsen  Forrest H. 《Plant and Soil》1997,193(1-2):199-208
This review describes the findings from human and animal studies indicating that B is a dynamic trace element which, in physiological amounts, can affect the metabolism or utilisation of numerous other substances involved in life processes including macrominerals, energy substrates such as triglycerides and glucose, nitrogen containing substances such as amino acids and proteins, reactive oxygen species, and estrogen. Through these effects, B can affect the function or composition of several body systems, including the brain, skeleton and immune system, generally in a beneficial fashion. Moreover, homeostatic mechanisms apparently exist for B because it is rapidly excreted in the urine, does not accumulate in tissues, and is maintained in a relatively narrow range of concentrations in blood of healthy individuals. Thus, even though B has not been conclusively established as essential because a biochemical function for it has not been identified, its beneficial actions suggest that an intake of over 1 mg day-1 (but probably not more than 13 mg day-1) is desirable; diets low in fruits, vegetables, legumes and nuts may not provide this amount of B. Boron may be of more practical nutritional importance than currently acknowledged.  相似文献   

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A nuclear binding (NB) assay has been developed for the measurement in intact viable cells of biologically active (functional) estrogen and progesterone receptors, i.e. those capable of binding to nuclear acceptor sites [Spelsberg et al., Endocrinology 121: 631 (1987)]. This paper describes the application of this assay to analyses of androgen receptors in the guinea pig seminal vesicle and in human prostatic carcinoma. Cells from fresh animal seminal vesicles or human prostate carcinoma are isolated using collagenase and are incubated with [3H]R1881 for 1 h at 22 degrees C, after which nuclei are isolated at 4 degrees C and assayed for DNA and radioactivity. This NB assay demonstrates a saturable, temperature dependent, steroid and tissue specific nuclear binding of [3H]R1881 for the guinea pig-seminal vesicle system. The nuclear binding is of high affinity and low capacity. The NB assay reveals several important aspects of the androgen and estrogen receptors in target tissues: (1) the nuclear acceptor sites for androgen receptor (AR) are steroid receptor specific; (2) there are different concentrations of the androgen and estrogen receptors between the epithelium and the fibromuscular components of the guinea pig seminal vesicle; and finally (3) some biopsies of human prostate cancer appear to contain biologically inactive AR. This assay may be useful in the analyses of functional receptors in biopsies of human cancer cells.  相似文献   

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The effects of cimetidine, a histamine H2 receptor antagonist, on human sex fibroblasts androgen receptors have been studied. It has been observed that cimeticline competes with dihydrotestosterone for the human fibroblast androgen receptor. This action may explain some side effects observed, in man, with this drug.  相似文献   

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During the last decade, multiple pattern recognition receptors (PRRs) have been identified. These are involved in the innate immune response against a plethora of pathogens. However, PRR functioning can also be detrimental, even during infections. This review discusses the current knowledge on PRRs that recognize dermatotropic pathogens, and potential therapeutical implications.  相似文献   

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