Post on 09-Aug-2019
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
Topics
Puberty
Melatonin
Leptin
My Pubertal Place
Changing relation between probable range of
menarcheal age and psychosocial transitions into
adulthood
George C Patton, Russell VinerLancet 2007; 369: 1130–39
Leptin
Adrenarche Gonadarche Skeletal growth
Schematic presentation of the reproductive
roles of leptin and ghrelin
Tena-Sempera M. Neuroendocrinology 2007;86:229–241
Pineal gland syncronizes seasonal reproduction with
optimum environmental conditions.
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.
Effects of Pinealectomy on Ghrelin in Arcuate
Nucleus
Aydin M. et al. Regul Pept 2008 Feb 7;146(1-3):197-203.
GnRH
Melatonin
NPY
LeptinGhrelin
-
-+
+-
alfa-MSH
+ +
(-)
- +
GnRH
Melatonin Kiss
GnIH
++
-
-
-?
KISS-MT Tango
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.
Obesity + More light = Early puberty
More leptin + Less melatonin = Early puberty
The questions
Does prepubertal leptin increase advance
puberty onset ?
Can pineal gland modify the effect of leptin on
puberty onset ?
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
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)
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
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
*
*
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
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
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
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 (%)
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.
Contributors
Haluk KELESTIMUR Bayram YILMAZ Ahmet AYAR
Mete Özcan Ertugrul KILIÇ
Ergul ALCIN Ulkan KILIÇ
Ramis ÇOLAK
Acknowledgement
(project # 107T825)
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