In:
Journal of Endocrinology, Bioscientifica, Vol. 187, No. 2 ( 2005-11), p. 293-302
Abstract:
The human skin holds the full machinery for pro-opiomelanocortin processing. The α-melanocyte-stimulating hormone (α-MSH)/melanocortin-1-receptor cascade has been implicated as a major player via the cAMP signal in the control of melanogenesis. Only very recently the β-endorphin/μ-opiate receptor signal has been added to the list of regulators of melanocyte dendricity and melanin formation. In this context it was reported that (6R)- l -erythro-5,6,7,8-tetrahydrobiopterin (6BH 4 ) can act as an allosteric inhibitor of tyrosinase, the key enzyme in melanogenesis, and this inhibition is reversible by both α- and β-MSH. It was also shown earlier that 7BH 4 , the isomer of 6BH 4 , is twice as active in this inhibition reaction. However, as yet it is not known whether 7BH 4 is indeed present in loco in the melanosome. We here provide evidence that this isomer is present in this organelle in a concentration range up to 50 × 10 −6 M. Determination of β-MSH in melanosomal extracts yielded 10 pg/mg protein. Moreover, we demonstrate reactivation of the 7BH 4 /tyrosinase inhibitor complex by β-MSH, whereas α-MSH failed to do so. Furthermore, we show intra-melanosomal l -dopa formation from dopachrome by 7BH 4 in a concentration range up to 134 × 10 −6 M. Based on these results, we propose a new receptor-independent mechanism in the control of tyrosinase/melanogenesis by β-MSH and the pterin 7BH 4 .
Type of Medium:
Online Resource
ISSN:
0022-0795
,
1479-6805
Language:
Unknown
Publisher:
Bioscientifica
Publication Date:
2005
detail.hit.zdb_id:
1474892-7
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