chronic leptin infusion advances puberty onset in sham and ... · chronic leptin infusion advances...
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Chronic leptin infusion advances puberty
onset in sham and pinealectomized
normally fed female rats
Haluk Kelestimur
Firat University
Faculty of Medicine
Department of Physiology
&
The Institute of Health Science
Department of Neuroendocrinology
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Topics
Puberty
Melatonin
Leptin
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My Pubertal Place
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Changing relation between probable range of
menarcheal age and psychosocial transitions into
adulthood
George C Patton, Russell VinerLancet 2007; 369: 1130–39
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Leptin
Adrenarche Gonadarche Skeletal growth
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Schematic presentation of the reproductive
roles of leptin and ghrelin
Tena-Sempera M. Neuroendocrinology 2007;86:229–241
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Pineal gland syncronizes seasonal reproduction with
optimum environmental conditions.
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Effects of Pinealectomy on Leptin in Anterior
Pituitary
Canpolat et al. Eur J Pharmacol. 2001 Sep 28;428(1):145-8.
Kus I et al. Physiol Res. 2004;53(4):403-8.
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Effects of Pinealectomy on Ghrelin in Arcuate
Nucleus
Aydin M. et al. Regul Pept 2008 Feb 7;146(1-3):197-203.
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GnRH
Melatonin
NPY
LeptinGhrelin
-
-+
+-
alfa-MSH
+ +
(-)
- +
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GnRH
Melatonin Kiss
GnIH
++
-
-
-?
KISS-MT Tango
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Puberty-Leptin-Melatonin
Precocious puberty is associated with high leptin
and low melatonin levels.
Delayed puberty is associated with low leptin
and higher melatonin levels.
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Obesity + More light = Early puberty
More leptin + Less melatonin = Early puberty
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The questions
Does prepubertal leptin increase advance
puberty onset ?
Can pineal gland modify the effect of leptin on
puberty onset ?
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No
rma
l P
ub
ert
yN
orm
al P
ub
ert
y
Leptin
Ea
rly P
ub
ert
yE
arl
y P
ub
ert
y
AGEP
ub
ert
y O
ns
et
Pu
be
rty O
ns
et
[Lep
tin
]
10 20 30 40 50 600Age
[Mela
ton
in]
A pubertal increase in
leptin and decrease
in melatonin gates onset
of puberty
HypothesisHypothesis
Does the admistration of
leptin to prepubertal
pinealectomized animals
advance puberty onset ?
MeleatoninTest
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15 day old
Wistar Female Rats 21st day
Subcutaneous osmotic pump
implantation
(0.25µl/hour, 1µg/day, 4 weeks)
Leptin
Leptin
Vehicle
PNX
SHAM
SHAM
Experimental Design
ExamineBody weight
Food intake
Day of VO
Oestrous cycle
Ovarian weight
Uterine weight
n=6)
n=5)
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Effect of leptin on vaginal opening in
pinealectomized rats
Day
27 28 29 30 31 32 33 34 35 36 37 38
Cu
mu
lati
ve
Va
gin
al O
pe
nin
g (
%)
0
20
40
60
80
100
Sham Leptin
Sham Vehicle
Pnx Leptin
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Vag
inal O
pen
ing
Med
ian
0
27
28
29
30
31
32
33
34
Pnx
Lep
tin
Sha
m L
eptin
Sha
m V
ehic
le
*
*
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Th
e B
od
y W
eig
hts
on
Th
e D
ay
o
f V
ag
inal
Op
en
ing
0
50
60
70
80
Pnx
Lep
tin
Sha
m L
eptin
Sha
m V
ehic
le
*
*
The body weights on the day of vaginal
opening
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Overi
an
Weih
t (m
g/1
00g
)
0
60
65
70
75
80
85
Pnx
Lep
tin
Sha
m L
eptin
Sha
m V
ehic
le
Ute
rin
e W
eih
t (m
g/1
00
g)
0
100
150
200
250
300
Pnx
Lep
tin
Sha
m L
eptin
Sha
m V
ehic
le
Effects of leptin on ovarian and uterine
weights
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Effect of leptin on cumulative food intake over
time
Day
21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
Fo
od
In
tak
e (
gr)
0
20
40
60
80
100
120
140
160Pnx Leptin
Sham Leptin
Sham Vehicle
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Day
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37
Bo
dy W
eig
ht
Ch
an
ge
(%
)
50
100
150
200
250
300
Pnx Leptin
Sham Leptin
Sham Vehicle
Effects of leptin on body weight change (%)
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Conclusions
Pre-weaning peripheral leptin infusion advances puberty onset.
Low leptin dose can advance puberty onset without affecting food intake.
Leptin-infused rats showed puberty in a low weight.
Leptin administration signals high fat store for brain in during weaning period.
Pinealectomy did not modify effect of leptin significantly.
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Contributors
Haluk KELESTIMUR Bayram YILMAZ Ahmet AYAR
Mete Özcan Ertugrul KILIÇ
Ergul ALCIN Ulkan KILIÇ
Ramis ÇOLAK
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Acknowledgement
(project # 107T825)
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