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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