Fig. 1
FSK (1 μM)
Mel (nM)
Luz (nM)
+ 0 0
+ 100
0
+ 100 100
+ 100 100 0
+ 0 1000 0
0.5 1 1.5
mRNA level (/RPL19)
PRL
A B
C
GH3 cells Rat whole pituitary
MM MT1 MT2 RPL19
* *
FSK (1 μM) Mel/Ram (μM)
- 0
+ 0
+ 10
+ 30
+ 100
mRNA level (/RPL19)
0 0.5 1
1.5 Mel
PRL
Ram**
*
#
# #
FSK
(1 μM)Ram
(nM)- 0
- 100
- 1000
+ 0
+ 100
+ 1000 FSK
(1 μM)Mel
(nM)- 0
- 100
- 1000
+ 0
+ 100
+ 100
0
Co nc en tr at io n (n g/ m l) Co nc en tr at io n (n g/ m l)
PRL
PRL
D
E
0 10 20 30 40 50
0 10 20 30 40 50
a a a
b
c c
a
b b
c
d d
322bp 224bp 190bp MM MT1 MT2 RPL19
IB: pSmad
1/5/8
IB: actin FSK(1 μM)
BMP-4 (100 ng/ml)
Mel (100 nM)
Ram (100 nM)
Luz (100 nM)
+ - -- -
+ + -- -
+ + +- -
+ + +- -
+ + -- +
+ + +- +
+ + +- +
A C
FSK (1 μM)
BMP-4 (ng/ml)
Mel (nM) Ram (nM)
- 0 0 0
- 100
0 0
+ 0 0 0
+ 100
0 0
+ 100 100 0
+ 100
0 100 0
50 100
150
Id-1
mRNA level (/RPL19)
B
a b
c cd
d
a
0 50
100
PRL
FSK (μM)
BMP-4 (ng/ml) Mel (nM)
Ram (nM)
- 0 0 0
- 100
0 0
+ 0 0 0
+ 100
0 0
+ 100 100 0
+ 100
0 100
b
a
b
ab a
* mRNA level (/RPL19) mRNA level (/RPL19)
0 0.5 1 1.5
2
MT2
BMP-4 (100 ng/ml)
- +
*
Fig. 2
E
0 0.5 1 1.5
FSK(1 μM) H-89(1 μM) U0126 (1 μM) SB203580 (1 μM) SP600125 (1 μM)
+- -- -
++ -- -
+- -- -
+- +- -
+- -- -
+- +- -
+- -- -
+- -- + mRNA level (/RPL19)
PRL
** * n.s. n.s.
0 30 60 90 120
FSK (1 μM) BMP-4 (ng/ml) Mel (nM) Ram (nM)
- 00 0
+ 00 0
+ 1000
0 + 00 100
+ 1000
0 + 100100
0 + 1000 100 -
00 0
B
cAMPlevel (nM)
b b
a a
b c
d d
A
0 2 4
+ +- FSK (1 μM)
Mel (100 nM) Ram (100 nM)
- --
+ --
+ +-
0 1 2 3 4 5
BMP-4 (ng/ml) Mel (nM) Ram (nM)
0 0 0
0 100
0 0 0 100
cAMPlevel (nM)
a b b
0 2 4 6 8
0 0 0
100 0 0
100 100 0
100 0 100
a
b b
a
BMP-4 Mel Ram
C
0 2 4 6 8 10
PRL
mRNA level (/RPL19)
BtcAMP(mM)
Mel (nM) Ram (nM)
0 00
0.1 00
0.1 1000
0.10 100
D
Relative intensity (pERK/ tERK)
b
a
b b
b a
b c
cAMPlevel (nM)
+- + FSK (1 μM)
Mel (100 nM) Ram (100 nM)
-- -
+- -
++ - IB: pERK
IB: tERK IB: pP38 IB: tP38 IB: pJNK IB: tJNK
Fig. 3
Fig. 4
- -
GH3 cells
PRL secretion
FSK
BMPRs
+ + P
Melatonin
AC
PKA ERK ERK
BtcAMP +
PRL promoter
