Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many melanocyte or skin equivalent models have been used to evaluate the potential efficacy of melanogenic compounds to regulate pigmentation, but there has been great variation in results, partially stemming from the use of different cell lines and diverse conditions for the melanogenic assays. In an earlier report, we optimized a microtiter format assay system to screen potential bioactive compounds using immortalized melan-a melanocytes. That assay system, termed the STOPR protocol, allowed effects on melanocyte proliferation and differentiation to be assessed in a highly sensitive, reproducible, and cost-effective manner. However, in the skin and hair, melanocytes interact with keratinocytes, fibroblasts, and other cell types, and testing of putative bioactive compounds on melanocytes alone in culture does not allow one to observe the interactions with those other cell types, such as would occur in vivo. Therefore, we developed a melanocyte-keratinocyte coculture protocol that allows testing of compounds for potential effects on pigmentation in a more physiologically relevant context. It is a sensitive, reproducible, and reliable model for testing melanogenic regulators, and we have standardized it with known melanogenic inhibitors (hydroquinone, arbutin, kojic acid, and niacinamide) and stimulators (alpha-melanocyte-stimulating hormone, 8-methoxypsoralen, and 3,4-dihydroxyphenylalanine). This coculture system allows for large-scale screening of candidate compounds in conjunction with the STOPR protocol and provides a more physiologically relevant system to study melanocyte-keratinocyte interactions and to elucidate the regulatory mechanisms of melanogenic compounds.
 ...
PMID:A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. 1205 55

Reconstituted 3-dimensional human skin equivalents containing melanocytes and keratinocytes on an artificial dermal substitute are gaining popularity for studies of skin metabolism because they exhibit morphological and growth characteristics similar to human epidermis. In this study, we show that such a pigmented epidermis model can be used to assess the regulation of pigmentation by known melanogenic compounds. In monolayers or in melanocyte-keratinocyte co-cultures, melanocyte-keratinocyte interactions are missing or are spatially limited. The commercial skin equivalents used in this study were derived from epidermal cells obtained from donors of three different ethnic origins (African- American, Asian, and Caucasian), and they reflect those distinct skin phenotypes. We used these pigmented human epidermis models to test compounds for potential effects on pigmentation in a more physiologically relevant context, which allows further characterization and validation of interesting melanogenic factors. We used known melanogenic stimulators (alpha-melanocyte-stimulating hormone and 3,4-dihydroxyphenylalanine) and inhibitors (hydroquinone, arbutin, kojic acid, and niacinamide) and examined their effects on the production of melanin and its distribution in upper layers of the skin. Our studies indicate that commercial skin equivalents provide a convenient and cost-effective alternative to animal testing for evaluating the regulation of mammalian pigmentation by melanogenic factors and for elucidating their mechanisms of action.
 ...
PMID:Reconstituted 3-dimensional human skin of various ethnic origins as an in vitro model for studies of pigmentation. 1281 30

Chloasma is a required hypermelanosis of sun-exposed areas occurred during pregnancy and it can affect 50-70% of pregnant women. It presents as symmetric hyperpigmented macules, which can confluent or punctuate. The most common locations are the cheeks, the upper lip, the chin and the forehead. The exact mechanism by which pregnancy affects the process of melanogenesis is unknown. Estrogen, progesterone, and melanocyte-stimulating hormone (MSH) levels are normally increased during the third trimester of pregnancy. However, nulliparous patients with chloasma have no increased levels of estrogen or MSH. In addition, the occurrence of melasma with estrogen- and progesterone-containing oral contraceptive pills has been reported. The observation that postmenopausal woman who are given progesterone develop melasma, while those who are given only estrogen do not, implicates progesterone as playing a critical role in the development of melasma. UV-B, UV-A, and visible light are all capable of stimulating melanogenesis. The condition is self-limited; however spontaneous resolution is time-consuming and may take months to resolve normal pigmentation. Therefore, it is worthwhile to prevent the onset of chloasma, by strict photoprotection. Prudent measures to avoid sun exposure include hats and other forms of shade combined with the application of a broad-spectrum sunscreen at least daily. Sunscreens containing physical blockers, such as titanium dioxide and zinc oxide, are preferred over chemical blockers because of their broader protection. Chloasma can be difficult to treat. Quick fixes with destructive modalities (eg, cryotherapy, medium-depth chemical peels, lasers) yield unpredictable results and are associated with a number of potential adverse effects. The mainstay of treatment remains topical depigmenting agents. Hydroquinone (HQ) is most commonly used.
 ...
PMID:Chloasma--the mask of pregnancy. 1914 Feb 77