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A Slominski

Publications and source records attributed to A Slominski.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hair cycle-dependent expression of corticotropin-releasing factor (CRF) and CRF receptors in murine skin.

We demonstrate the presence and hair cycle-dependent expression of corticotropin-releasing factor (CRF) and CRF receptors (CRF-R) in C57BL/6 mouse skin. To correlate this with a physiological, developmentally controlled tissue remodeling process, we have analyzed CRF and CRF-R expression during defined stages of the murine hair cycle with its rhythmic changes between growth (anagen), regression (catagen), and resting (telogen). Using reversed-phase HPLC combined with two independent anti-CRF radioimmunoassays, we have identified CRF in murine skin. Maximal CRF levels were found in anagen III-IV skin, and minimal values were detected in catagen and telogen skin. By immunofluorescence, maximal CRF immunoreactivity (CRF-IR) was seen in the basal epidermis, nerve bundles of skin, the outer root sheath and matrix region of anagen IV-VI follicles, and in defined sections of their perifollicular neural network, whereas catagen and telogen skin displayed minimal CRF-IR. Using quantitative autoradiography and 125I-CRF as a tracer, high-affinity binding sites for CRF were detected in murine skin. The highest density of specific binding sites was detected in the panniculus carnosus, the epidermis, and the hair follicle. CRF-R type 1 (CRF-R1) IR was detected by immunohistology mainly in the outer root sheath, hair matrix, and dermal papilla of anagen VI follicles, as well as in the inner and outer root sheaths of early catagen follicles. CRF-R1 expression was also hair cycle dependent. Therefore, in normal murine skin, the CRF-CRF-R signaling system may operate as an additional neuroendocrine pathway regulating skin functions, possibly in the context of cutaneous stress responses.

Animals↗
PubMed1998

What controls melanogenesis?

The pigments eumelanin and pheomelanin are the visually most striking products of specialized neural crest-derived cells (melanocytes), and provide color to both epidermis and hair shafts. While the intriguing and controversial biological functions of these multifaceted heteropolymers will be discussed in a later feature, here it is explored how their generation (melanogenesis) is controlled. For decades, this has been the object of much controversy, the salient features of which are delineated in the following contributions.

Animals↗
PubMed1998

Characterization of corticotropin-releasing hormone (CRH) in human skin.

We have confirmed the expression of CRH and CRH receptor type 1 genes in human skin, cultured HaCaT keratinocytes, squamous cell carcinoma, and melanoma cells. The size of CRH messenger ribonucleic acid (mRNA), estimated by Northern blot hybridization, was 1.5 kilobases. CRH peptide was identified by reverse phase high pressure liquid chromatography separation in both whole skin and cultured cells. Forskolin and dexamethasone at concentrations of 10 micromol/L stimulated and inhibited, respectively, CRH peptide production in squamous cell carcinoma and melanoma cells, but had no significant effect on the CRH mRNA level. In melanoma cells, stimulation of melanogenesis down-regulated CRH receptor type 1 mRNA expression, but was without effect on CRH mRNA production. We suggest that in human skin the CRH signaling system is both operative and under regulatory control.

Blotting, Northern↗
PubMed1997

Identification and measurement of beta-endorphin levels in the skin during induced hair growth in mice.

We describe new and effective techniques for extracting proopiomelanocortin (POMC)-derived peptides from mammaliar skin. Using this methodology (hot-acid extraction) and two independent HPLC-controlled RIA systems, we identify beta-endorphin peptide in mammalian skin and demonstrate significant hair cycle-dependent fluctuations in both the skin concentration and the in situ expression pattern of beta-endorphin (sebaceous glands) during the entire murine hair cycle. The observed anagen (growth phase) associated increase in beta-endorphin concentration and its decline during the follicle involution (catagen) or resting (telogen) phase raise the possibility of a regulatory function of this neuropeptide in cyclic changes of skin physiology.

Animals↗
PubMed1997

Production of POMC, CRH-R1, MC1, and MC2 receptor mRNA and expression of tyrosinase gene in relation to hair cycle and dexamethasone treatment in the C57BL/6 mouse skin.

In skin of the C57BL/6 mouse, the production of mRNA transcripts that hybridized to the coding region of the MC1 receptor (MC1-R) gene was undetectable in telogen, increased during hair growth, and, after reaching the highest values in anagen VI, decreased during the anagen-catagen transition phase. This production was associated with anagen-dependent expression of the tyrosinase gene and enzyme activity. In contrast, the production of 4.5- and 2.0-kb mRNAs hybridizable to the coding region of the MC2 receptor (MC2-R) gene was similar throughout the entire hair cycle. Previously, dexamethasone was demonstrated to induce premature catagen development accompanied by an abrupt termination of melanogenesis. Here we demonstrate that topical application of dexamethasone during anagen VI decreased the concentration of POMC, MC1-R, and tyrosinase mRNA in the skin. The decrease in tyrosinase mRNA concentration was accompanied by a decrease in tyrosinase protein concentration and enzyme activity. These results support the hypothesis that murine hair growth and attendant melanogenesis can be regulated through coordinated changes in local expression of POMC, MC1-R, and tyrosinase genes.

Animals↗
PubMed1996

Production and release of proopiomelanocortin (POMC) derived peptides by human melanocytes and keratinocytes in culture: regulation by ultraviolet B.

It is demonstrated that ultraviolet B (UVB) radiation stimulates increased expression of the proopiomelanocortin (POMC) gene which is accompanied by production and release of alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) by both normal and malignant human melanocytes and keratinocytes. The production and release of both peptides are also stimulated by dibutyryl cyclic adenosine monophosphate (dbcAMP) and interleukin 1 alpha (IL-1 alpha) but not by endothelin-1 (ET-1) or tumor necrosis factor-alpha (TNF-alpha). N-acetyl-cysteine (NAC), a precursor of glutathione (GSH), an intracellular free radical scavenger, abolishes the UVB-stimulated POMC peptide production and secretion. Conclusions are as follows: (1) Cultured human cells of cutaneous origin, namely keratinocytes and melanocytes, can produce and express POMC; (2) POMC expression is enhanced by exposure to UVB, possibly through a cyclic AMP-dependent pathway; and (3) The action of UVB on POMC production may involve a cellular response to oxidative stress.

Acetylcysteine↗
PubMed1996

Metabolism of serotonin to N-acetylserotonin, melatonin, and 5-methoxytryptamine in hamster skin culture.

Biotransformation of [3H]serotonin by cultured hamster skin to 3H-metabolites corresponding to N-acetylserotonin (NAS), melatonin, and 5-methoxytryptamine (5-MT) was demonstrated. This process was time-dependent, with the highest production of radioactive NAS and melatonin metabolites after 3 and 5 h of incubation followed by a decrease in the rate of metabolite release into the media. Conversely, the formation of radioactive metabolite corresponding to 5-MT increased gradually during skin culture, reaching the highest level after 24 h of incubation. The production of 3H-metabolites, corresponding to NAS, melatonin, and 5-MT, was stimulated by forskolin with a maximum effect of forskolin at 10 microM concentration. The gas chromatographic/mass spectroscopy analysis of the fraction eluting at the retention time of NAS standard material showed that it contained NAS, further confirming production and release of NAS into the media by hamster skin. Therefore, we conclude that mammalian skin can acetylate serotonin to NAS and postulate that the NAS is further metabolized by the skin to form melatonin which is subsequently transformed to 5-MT.

5-Methoxytryptamine↗
PubMed1996

The expression of proopiomelanocortin (POMC) and of corticotropin releasing hormone receptor (CRH-R) genes in mouse skin.

The proopiomelanocortin (POMC) and the corticotropin releasing hormone receptor (CRH-R) genes are expressed in the skin of the C57BL/6 mouse throughout the entire hair cycle, and CRH immunoreactivity is present in the pilosebaceous unit of the hair follicle and the epidermis. These findings suggest that some components of hypothalamo-pituitary axis are operating in mouse skin.

Animals↗
PubMed1996

Pharmacological disruption of hair follicle pigmentation by cyclophosphamide as a model for studying the melanocyte response to and recovery from cytotoxic drug damage in situ.

Here we show that cyclophosphamide induces disruption of follicular melanogenesis, which is characterized by abnormal transfer of pigment granules to ectopic hair bulb locations, extrafollicular melanin incontinence, disordered formation of melanosomes, and inhibition of melanosome transfer into precortical keratinocytes. This is in contrast to dexamethasone-induced termination of follicle melanogenesis, which activates premature but predominantly normal catagen development. Cyclophosphamide-induced pigmentation disruption was accompanied by significant alterations of biochemical and biophysical markers of melanogenesis, compared to control mice treated either with vehicle or with topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a decline in the melanin signal and predominant eumelanin production. Tyrosine hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole carboxylic acid conversion factor activity remains unchanged in cyclophosphamide-treated mice compared to controls. These observations emphasize the key role of tyrosinase as opposed to postdihydroxyphenylalanine oxidase steps in normal and pathological termination of melanogenesis and shows that tyrosinase is the most sensitive target of the melanogenic apparatus for pharmacological regulation. Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after a new anagen hair bulb has been constructed, which points to the existence of a relatively chemoresistant melanoblast-like cell population residing in the noncycling part of the hair follicle.

Animals↗
PubMed1996

ACTH receptor, CYP11A1, CYP17 and CYP21A2 genes are expressed in skin.

Evidence is provided that mRNA for ACTH (MC-2) receptor and mRNAs for three obligatory enzymes of steroid synthesis including cytochromes P450scc, P450c17 and P450c21 are expressed in normal and pathologic human skin. Thus, molecular elements of the distal loop of the "pituitary-adrenal axis" such as the MC-2, CYP11A1, CYP17 and CYP21A2 genes are expressed in the skin.

Base Sequence↗
PubMed1995

Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin.

Evidence is provided that human skin, the largest body organ exposed to multiple stressors, expresses proopiomelanocortin (POMC), corticotropin releasing hormone (CRH) and CRH-receptor (CRHR) genes in vivo. In vitro studies show that POMC and CRHR mRNAs are transcribed in melanocytes, cells derived from the neural crest, and in keratinocytes, cells derived from the ectoderm. CRH mRNA is transcribed in cultured melanocytes but not in keratinocytes. It is proposed that an equivalent of the 'hypothalamus-pituitary axis' composed of the CRH-CRHR-POMC loop is conserved in mammalian skin.

Base Sequence↗
PubMed1995

Cutaneous melanoma: pathology, relevant prognostic indicators and progression.

Malignant melanoma, one of the most rapidly increasing malignancies in man, has recently received substantial attention in the world literature concerning application of traditional morphologic and newer immunologic and molecular biologic methods of predicting progression and ultimate clinical outcome. Although clinical features of patient sex, age and anatomic site of the lesion are important, classic morphologic variables defining prognosis remain the cornerstone of predicting disease outcome. Extent of radial growth phase and the two microstaging methods of measuring tumor thickness and determining level of invasion remain the critical disease progression predictors. Assessment of mitotic rate, number of tumor infiltrating lymphocytes, and determining the presence of regression, ulceration, and epithelioid cell component, microscopic satellites and vascular invasion are also important. More recently a variety of molecular and biochemical prognostic markers have been cited for prediction of disease recurrence and metastasis. Both overexpression and down regulation of a variety of cell adhesion molecules have been implicated in disease progression as has alterations in the plasminogen activation system. A series of growth factors, growth factor receptors, oncogenes and tumor suppressor genes have also been considered. Structural and numerical genomic DNA abnormalities, cell proliferation markers and DNA ploidy status have also been considered. Recently a variety of serum and blood markers indicating disease persistence or progression have been studied including melanin synthesis precursors and intermediate compounds of melanogenesis. Molecular detection by PCR of melanogenesis specific mRNA may become the most sensitive prognostic marker of the future. At present histopathologic and clinical criteria remain the cornerstones of predicting prognosis in malignant melanoma.

Disease Progression↗
PubMed1995

Ultraviolet B and melanocyte-stimulating hormone (MSH) stimulate mRNA production for alpha MSH receptors and proopiomelanocortin-derived peptides in mouse melanoma cells and transformed keratinocytes.

Cell lines of cutaneous origin, namely melanocytes and keratinocytes, were previously demonstrated to exhibit functional melanocyte-stimulating hormone (MSH) receptors that are up-regulated by ultraviolet (UV) radiation and by MSH itself. In this study, it is demonstrated that UVB irradiation, exposure to MSH, or exposure to N6,O2-dibutyryl cyclic adenosine monophosphate stimulates production of mRNAs for both alpha MSH receptors and proopiomelanocortin in cultured mouse Cloudman S91 melanoma cells, and that UVB stimulates production and release of MSH and adrenocorticotropin peptides in both melanoma cells and transformed PAM 212 mouse keratinocytes. The results add support to the hypothesis that the effects of UVB on cutaneous melanogenesis are mediated through a series of coordinated events in which MSH receptors and proopiomelanocortin-derived peptides play a central role.

Animals↗