TY - JOUR
T1 - Stimulation of S91 melanoma tyrosinase activity by superpotent α-melanotropins
AU - Marwan, Mohamed M.
AU - Abdel Malek, Zalfa A.
AU - Kreutzfeld, Kristie L.
AU - Hadley, Mac E.
AU - Wilkes, Brian C.
AU - Hruby, Victor J.
AU - Castrucci, Ana Maria de L.
N1 - Funding Information:
Supportedin part by U.S. Public Health Service Grant AM17420a nd by National ScienceF ounda-tion grantsP CM-8112200a nd PCM-8110708D. r.
PY - 1985/7
Y1 - 1985/7
N2 - α-Melanocyte-stimulating hormone (α-MSH, α-melanotropin), [Nle4,D-Phe7]-α-MSH and related fragment analogues, Ac-[Nle4,D-Phe7]-α-MSH4-11-NH2 and Ac-[Nle4,D-Phe7]-α-MSH4-10-NH2, were studied for their ability to stimulate tyrosinase activity in Cloudman S91 mouse melanoma cells in tissue culture. All of the melanotropins stimulated tyrosinase activity in a dose-dependent manner. [Nle4,D-Phe7]-α-MSH was about 100 times more active than a-MSH as determined from the minimal effective dose (MED) required to activate the enzyme above control (basal) levels. The MED of this analogue to significantly stimulate tyrosinase activity at 24, 48 and 72 h of incubation was 10-11 M whereas the MED of α-MSH was 10-9 M at each of these times. The maximum tyrosinase activity achieved from the time of initial incubation in the presence of [Nle4,D-Phe7]-α-MSH was approximately 3-, 5- and 6-fold greater than control levels at 24, 48 and 72 h, respectively. The 2 [Nle4,D-Phe7]-substituted fragment analogues were at least as active as the tridecapeptide analogue and therefore at least 100-fold more active than a-MSH in stimulating enzyme activity. These [Nle4,D-Phe7]-substituted analogues were more active in the melanoma tyrosinase assay than in the melanoma adenylate cyclase assay or other normal melanocyte (frog and lizard skin) bioassays.
AB - α-Melanocyte-stimulating hormone (α-MSH, α-melanotropin), [Nle4,D-Phe7]-α-MSH and related fragment analogues, Ac-[Nle4,D-Phe7]-α-MSH4-11-NH2 and Ac-[Nle4,D-Phe7]-α-MSH4-10-NH2, were studied for their ability to stimulate tyrosinase activity in Cloudman S91 mouse melanoma cells in tissue culture. All of the melanotropins stimulated tyrosinase activity in a dose-dependent manner. [Nle4,D-Phe7]-α-MSH was about 100 times more active than a-MSH as determined from the minimal effective dose (MED) required to activate the enzyme above control (basal) levels. The MED of this analogue to significantly stimulate tyrosinase activity at 24, 48 and 72 h of incubation was 10-11 M whereas the MED of α-MSH was 10-9 M at each of these times. The maximum tyrosinase activity achieved from the time of initial incubation in the presence of [Nle4,D-Phe7]-α-MSH was approximately 3-, 5- and 6-fold greater than control levels at 24, 48 and 72 h, respectively. The 2 [Nle4,D-Phe7]-substituted fragment analogues were at least as active as the tridecapeptide analogue and therefore at least 100-fold more active than a-MSH in stimulating enzyme activity. These [Nle4,D-Phe7]-substituted analogues were more active in the melanoma tyrosinase assay than in the melanoma adenylate cyclase assay or other normal melanocyte (frog and lizard skin) bioassays.
KW - MSH
KW - melanin
KW - melanocyte-stimulating hormone
KW - melanogenesis
KW - melanotropin
KW - tyrosinase
UR - http://www.scopus.com/inward/record.url?scp=0021881908&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021881908&partnerID=8YFLogxK
U2 - 10.1016/0303-7207(85)90020-6
DO - 10.1016/0303-7207(85)90020-6
M3 - Article
C2 - 3926559
AN - SCOPUS:0021881908
SN - 0303-7207
VL - 41
SP - 171
EP - 177
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 2-3
ER -