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Insulin-like growth factor 1 (IGF-1): a growth hormone

Insulin-like growth factor 1 (IGF-1): a growth hormone

Z Laron

Abstract
Aim T o con t r ibu t e t o t h e deba t e a bou t w h et h er g r ow t h h or m on e (GH) a n d in su lin -lik e g r ow t h fa ct or 1
(IGF-1 ) a ct in depen den t ly on t h e g r ow t h pr ocess.
Methods T o descr ibe g r ow t h in h u m a n a n d a n im a l m odels of isola t ed IGF-1 deficien cy (IGHD), su ch a s
in La r on sy n dr om e (LS; pr im a r y IGF-1 deficien cy a n d GH r esist a n ce) a n d IGF-1 g en e or GH r ecept or
g en e k n ock ou t (KO) m ice.
Res ults Sin ce t h e descr ipt ion of LS in 1 9 6 6 , 5 1 pa t ien t s w er e follow ed, m a n y sin ce in fa n cy . New bor n s
w it h LS a r e sh or t er (4 2 4 7 cm ) t h a n h ea lt h y ba bies (4 9 5 2 cm ), su g g est in g t h a t IGF-1 h a s som e
in flu en ce on in t r a u t er in e g r ow t h . New bor n m ice w it h IGF-1 g en e KO a r e 3 0 % sm a ller . T h e post n a t a l
g r ow t h r a t e of pa t ien t s w it h LS is v er y slow , t h e dist a n ce fr om t h e low est n or m a l cen t ile in cr ea sin g
pr og r essiv ely . If u n t r ea t ed, t h e fin a l h eig h t is 1 0 0 1 3 6 cm for fem a le a n d 1 0 9 1 3 8 cm for m a le
pa t ien t s. T h ey h a v e a cr om icia , or g a n om icr ia in clu din g t h e br a in , h ea r t , g on a ds, g en it a lia , a n d
r et a r da t ion of sk elet a l m a t u r a t ion . T h e a v a ila bilit y of biosy n t h et ic IGF-1 sin ce 1 9 8 8 h a s en a bled it t o
be a dm in ist er ed t o ch ildr en w it h LS. It a cceler a t ed lin ea r g r ow t h r a t es t o 8 9 cm in t h e fir st y ea r of
t r ea t m en t , com pa r ed w it h 1 0 1 2 cm /y ea r du r in g GH t r ea t m en t of IGHD. T h e g r ow t h r a t e in follow in g
y ea r s w a s 5 6 .5 cm /y ea r .
Conclus ionIGF-1 is a n im por t a n t g r ow t h h or m on e, m edia t in g t h e pr ot ein a n a bolic a n d lin ea r g r ow t h
pr om ot in g effect of pit u it a r y GH. It h a s a GH in depen den t g r ow t h st im u la t in g effect , w h ich w it h
r espect t o ca r t ila g e cells is possibly opt im ised by t h e sy n er g ist ic a ct ion w it h GH.
Key words: in su lin -lik e

g r ow t h fa ct or I, g r ow t h h or m on es, La r on sy n dr om e, g r ow t h

In r ecen t y ea r s, n ew t ech n olog ies h a v e en a bled m a n y a dv a n ces in t h e so ca lled g r ow t h h or m on e (GH)

a x is (fig 1

). T h u s, it h a s been fou n d t h a t GH secr et ion fr om t h e a n t er ior pit u it a r y is r eg u la t ed n ot

on ly by GH r elea sin g h or m on e (GHRH) a n d som a t ost a t in (GH secr et ion in h ibit in g h or m on e), 1 bu t a lso
by ot h er h y pot h a la m ic pept ides ca lled GH secr et a g og u es, 2 w h ich seem t o a ct in sy n er g ism w it h GHRH 3
by in h ibit in g som a t ost a t in . 4 On e of t h ese h a s been clon ed a n d n a m ed Gh r elin . 5 T h e in t er pla y bet w een
GHRH a n d som a t ost a t in in du ces a pu lsa t ile GH secr et ion , 6 w h ich is h ig h est du r in g pu ber t y . GH
in du ces t h e g en er a t ion of in su lin -lik e g r ow t h fa ct or 1 (IGF-1 , a lso ca lled som a t om edin 1 ) in t h e liv er
a n d r eg u la t es t h e pa r a cr in e pr odu ct ion of IGF-1 in m a n y ot h er t issu es. 7

Fi gur e 1
The c asc ade of the gr ow th hor mone ax i s. CN S, c entr al ner v ous sy stem; GH, gr ow th hor mone; GHBP, GH
b i ndi ng pr otei n; GH-S, GH sec r etagogues; IGF-1 , i nsul i n-l i k e gr ow th f ac tor 1 ; IGFBPs, IGF b i ndi ng
pr otei ns; +, sti mul ati on; , i nhi b i ti on.

IGF-1
IGF-1 a n d IGF-2 w er e iden t ified in 1 9 5 7 by Sa lm on a n d Da u g h a da y 8 a n d desig n a t ed su lph a t ion
fa ct or by t h eir a bilit y t o st im u la t e

35-su lph a t e

in cor por a t ion in t o r a t ca r t ila g e. Fr oesch et al descr ibed

t h e n on -su ppr essible in su lin -lik e a ct iv it y (NSILA ) of t w o solu ble ser u m com pon en t s (NSILA I a n d II). 9 In
1 9 7 2 , t h e la bels su lph a t ion fa ct or a n d NSILA w er e r epla ced by t h e t er m som a t om edin , den ot in g a
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Insulin-like growth factor 1 (IGF-1): a growth hormone

su bst a n ce u n der con t r ol a n d m edia t in g t h e effect s of GH. 10 In 1 9 7 6 , Rin der k n ech t a n d Hu m bel 11
isola t ed t w o a ct iv e su bst a n ces fr om h u m a n ser u m , w h ich ow in g t o t h eir st r u ct u r a l r esem bla n ce t o
pr oin su lin w er e r en a m ed in su lin -lik e g r ow t h fa ct or 1 a n d 2 (IGF-1 a n d 2 ). IGF-1 is t h e m edia t or of
t h e a n a bolic a n d m it og en ic a ct iv it y of GH. 12

CHEMICAL STRUCTURE
T h e IGFs a r e m em ber s of a fa m ily of in su lin r ela t ed pept ides t h a t in clu de r ela x in a n d sev er a l pept ides
isola t ed fr om low er in v er t ebr a t es. 13 IGF-1 is a sm a ll pept ide con sist in g of 7 0 a m in o a cids w it h a
m olecu la r w eig h t of 7 6 4 9 Da . 14 Sim ila r t o in su lin , IGF-1 h a s a n A a n d B ch a in con n ect ed by disu lph ide
bon ds. T h e C pept ide r eg ion h a s 1 2 a m in o a cids. T h e st r u ct u r a l sim ila r it y t o in su lin ex pla in s t h e
a bilit y of IGF-1 t o bin d (w it h low a ffin it y ) t o t h e in su lin r ecept or .

THE IGF-1 GENE

T h e IGF-1 g en e is on t h e lon g a r m of ch r om osom e 1 2 q2 3 2 3 . 15,16 T h e h u m a n IGF-1 g en e con sist s of six
ex on s, in clu din g t w o lea der ex on s, a n d h a s t w o pr om ot er s. 17

IGF binding proteins (IGFBPs)

In t h e pla sm a , 9 9 % of IGFs a r e com plex ed t o a fa m ily of bin din g pr ot ein s, w h ich m odu la t e t h e
a v a ila bilit y of fr ee IGF-1 t o t h e t issu es. T h er e a r e six bin din g pr ot ein s. 18 In h u m a n s, a lm ost 8 0 % of
cir cu la t in g IGF-1 is ca r r ied by IGFBP-3 , a t er n a r y com plex con sist in g of on e m olecu le of IGF-1 , on e
m olecu le of IGFBP-3 , a n d on e m olecu le of a n 8 8 k Da pr ot ein n a m ed a cid la bile su bu n it . 19 IGFBP-1 is
r eg u la t ed by in su lin a n d IGF-1 20; IGFBP-3 is r eg u la t ed m a in ly by GH bu t a lso t o som e deg r ee by IGF-1 . 21

The IGF-1 receptor

T h e h u m a n IGF-1 r ecept or (t y pe 1 r ecept or ) is t h e pr odu ct of a sin g le copy g en e spa n n in g ov er 1 0 0 k b of
g en om ic DNA a t t h e en d of t h e lon g a r m of ch r om osom e 1 5 q2 5 2 6 . 22 T h e g en e con t a in s 2 1 ex on s (fig 2
) a n d it s or g a n isa t ion r esem bles t h a t of t h e st r u ct u r a lly r ela t ed in su lin r ecept or (fig 3 ). 23 T h e t y pe 1
IGF r ecept or g en e is ex pr essed by a lm ost a ll t issu es a n d cell t y pes du r in g em br y og en esis. 24 In t h e liv er ,
t h e or g a n w it h t h e h ig h est IGF-1 lig a n d ex pr ession , IGF-1 r ecept or m RNA is a lm ost u n det ect a ble,
possibly beca u se of t h e dow n r eg u la t ion of t h e r ecept or by t h e loca l pr odu ct ion of IGF-1 . T h e t y pe 1 IGF
r ecept or is a h et er ot et r a m er com posed of t w o ex t r a cellu la r spa n n in g su bu n it s a n d t r a n sm em br a n e
su bu n it s. T h e su bu n it s h a v e bin din g sit es for IGF-1 a n d a r e lin k ed by disu lph ide bon ds (fig 3 ). T h e
su bu n it h a s a sh or t ex t r a cellu la r dom a in , a t r a n sm em br a n e dom a in , a n d a n in t r a cellu la r dom a in . T h e
in t r a cellu la r pa r t con t a in s a t y r osin e k in a se dom a in , w h ich con st it u t es t h e sig n a l t r a n sdu ct ion
m ech a n ism . Sim ila r t o t h e in su lin r ecept or , t h e IGF-1 r ecept or u n der g oes lig a n d in du ced
a u t oph osph or y la t ion . 25 T h e a ct iv a t ed IGF-1 r ecept or is ca pa ble of ph osph or y la t in g ot h er t y r osin e
con t a in in g su bst r a t es, su ch a s in su lin r ecept or su bst r a t e 1 (IRS-1 ), a n d con t in u es a ca sca de of en zy m e
a ct iv a t ion s v ia ph osph a t idy lin osit ol-3 k in a se (PI3 -k in a se), Gr b2 (g r ow t h fa ct or r ecept or bou n d pr ot ein
2 ), Sy p (a ph oph ot y r osin e ph osph a t a se), Nck (a n on cog en ic pr ot ein ), a n d Sh c (sr c h om olog y dom a in
pr ot ein ), w h ich a ssocia t ed t o Gr b2 , a ct iv a t es Ra f, lea din g t o a ca sca de of pr ot ein k in a ses in clu din g Ra f,
m it og en a ct iv a t ed pr ot ein (MA P) k in a se, 5 G k in a se, a n d ot h er s. 26

Fi gur e 2
Ty pe 1 i nsul i n-l i k e gr ow th f ac tor r ec eptor gene and mRN A . Repr oduc ed w i th per mi ssi on f r om
W er ner .22

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Insulin-like growth factor 1 (IGF-1): a growth hormone

Fi gur e 3
Resemb l anc e b etw een the i nsul i n and i nsul i n-l i k e gr ow th f ac tor 1 (IGF-1 ) r ec eptor s.

Physiology
IGF-1 is secr et ed by m a n y t issu es a n d t h e secr et or y sit e seem s t o det er m in e it s a ct ion s. Most IGF-1 is
secr et ed by t h e liv er a n d is t r a n spor t ed t o ot h er t issu es, a ct in g a s a n en docr in e h or m on e. 27 IGF-1 is a lso
secr et ed by ot h er t issu es, 28 in clu din g ca r t ila g en ou s cells, a n d a ct s loca lly a s a pa r a cr in e h or m on e (fig 4
). 29 It is a lso a ssu m ed t h a t IGF-1 ca n a ct in a n a u t ocr in e m a n n er a s a n on cog en e. 30 T h e r ole of IGF-1 in
t h e m et a bolism of m a n y t issu es in clu din g g r ow t h h a s been r ev iew ed r ecen t ly . 31,32
Fi gur e 4
Par ac r i ne i nsul i n-l i k e gr ow th f ac tor 1 (IGF-1 ) sec r eti on and endoc r i ne IGF-1 tar gets i n the v ar i ous
zones of the epi phy seal c ar ti l age gr ow th zone.

T h e follow in g is a n a n a ly sis of w h et h er IGF-1 , t h e a n a bolic effect or h or m on e of pit u it a r y GH, is t h e

r ea l g r ow t h h or m on e .

Is IGF-1 a or the growth hormone?

T h e discu ssion on t h e r ole of IGF-1 in body g r ow t h w ill be ba sed on g r ow t h in st a t es of IGF-1 deficien cy
a n d t h e effect s of ex og en ou s IGF-1 a dm in ist r a t ion . Ex per im en t s in n a t u r e (g en e delet ion or g en e
m u t a t ion s) or ex per im en t a l m odels in a n im a ls, su ch a s g en e k n ock ou t s, h elp u s in t h is en dea v ou r . In
1 9 6 6 a n d 1 9 6 8 , 33,34 w e descr ibed a n ew t y pe of dw a r fism in dist in g u ish a ble fr om g en et ic isola t ed GH
deficien cy (IGHD), bu t ch a r a ct er ised by h ig h ser u m GH v a lu es. Su bsequ en t st u dies r ev ea led t h a t t h ese
pa t ien t s ca n n ot g en er a t e IGF-1 . 35
T h is sy n dr om e of GH r esist a n ce (in sen sit iv it y ) w a s n a m ed by Elder s et al a s La r on dw a r fism , 36 a n a m e
su bsequ en t ly ch a n g ed t o La r on sy n dr om e (LS). 37 Molecu la r st u dies r ev ea led t h a t t h e ca u ses of GH
r esist a n ce a r e delet ion s38 or m u t a t ion s39 in t h e GH r ecept or g en e, r esu lt in g in t h e fa ilu r e t o g en er a t e
IGF-1 a n d a r edu ct ion in t h e sy n t h esis of sev er a l ot h er su bst a n ces, in clu din g IGFBP-3 . T h is u n iqu e
m odel in h u m a n s h a s en a bled t h e st u dy of t h e differ en t ia l effect s of GH a n d IGF-1 .

Growth and development in congenital (primary) IGF-1 deficiency (LS)

Ou r g r ou p h a s st u died a n d follow ed 5 2 pa t ien t s (m a n y sin ce bir t h ) t h r ou g h ou t ch ildh ood, pu ber t y , a n d
in t o a du lt h ood. W e fou n d t h a t n ew bor n s w it h LS a r e slig h t ly sh or t er a t bir t h (4 2 4 7 cm ) t h a n h ea lt h y
ba bies (4 9 5 2 cm ), su g g est in g t h a t IGF-1 h a s som e in flu en ce on in t r a u t er in e lin ea r g r ow t h . 40 T h is fa ct
is en for ced by t h e fin din g s t h a t a lr ea dy a t bir t h , a n d t h r ou g h ou t ch ildh ood, sk elet a l m a t u r a t ion is
r et a r ded, a s is or g a n g r ow t h . 41 T h ese g r ow t h a bn or m a lit ies in clu de a sm a ll br a in (a s ex pr essed by h ea d
cir cu m fer en ce), 41 a sm a ll h ea r t (ca r diom icr ia ), 42 a n d a cr om icr ia (sm a ll ch in , r esu lt in g fr om
u n der dev elopm en t of t h e fa cia l bon es, sm a ll h a n ds, a n d sm a ll feet ). 33,34 IGF-1 deficien cy a lso ca u ses
u n der dev elopm en t a n d w ea k n ess of t h e m u scu la r sy st em , 43 a n d im pa ir s a n d w ea k en s h a ir 44 a n d n a il
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g r ow t h . T h ese fin din g s a r e iden t ica l t o t h ose descr ibed in IGHD. 45 IGF-1 deficien cy t h r ou g h ou t
ch ildh ood ca u ses dw a r fism (fin a l h eig h t if u n t r ea t ed, 1 0 0 1 3 5 cm in fem a le a n d 1 1 0 1 4 2 cm in m a le
pa t ien t s), 40,41 w it h a n a bn or m a lly h ig h u pper t o low er body r a t io. 41 On e pa t ien t r epor t ed fr om t h e UK
w a s fou n d t o h a v e a delet ion of ex on s 4 a n d 5 of t h e IGF-1 g en e a n d h e t oo w a s fou n d t o h a v e sev er e
g r ow t h r et a r da t ion . 46
Im pa ir ed g r ow t h a n d sk elet a l dev elopm en t in t h e a bsen ce of IGF-1 w er e con fir m ed in m ice u sin g
k n ock ou t (KO) of t h e IGF-1 g en e or GH r ecept or g en e. 4749
Kn ock ou t of t h e IGF-1 g en e or t h e IGF-1 r ecept or g en e r edu ces t h e size of m ice by 4 0 4 5 %. 49 La ck of t h e
IGF-1 r ecept or is let h a l a t bir t h in m ice ow in g t o r espir a t or y fa ilu r e ca u sed by im pa ir ed dev elopm en t of
t h e dia ph r a g m a n d in t er cost a l m u scles. 49 In a n ot h er m odel, t h e m ice r em a in ed a liv e a n d t h eir
post n a t a l g r ow t h w a s r edu ced. 50
In con clu sion , fin din g s in h u m a n s a n d in a n im a ls sh ow t h a t IGF-1 deficien cies ca u ses pr on ou n ced
g r ow t h r et a r da t ion in t h e pr esen ce of in cr ea sed GH v a lu es.
T h e follow in g is a su m m a r y of t h e r esu lt s of t h e g r ow t h st im u la t in g effect s of t h e a dm in ist r a t ion of
ex og en ou s IGF-1 t o ch ildr en a n d ex per im en t a l da t a .

Growth promoting effects of IGF-1

T h e fir st dem on st r a t ion t h a t ex og en ou s IGF-1 st im u la t es g r ow t h w a s t h e a dm in ist r a t ion of pu r ified
h or m on e t o h y poph y sect om ised r a t s. 51,52 A ft er t h e biosy n t h esis of IGF-1 iden t ica l t o t h e n a t iv e
h or m on e, 53 t r ia ls of it s u se in h u m a n s w er e beg u n ; fir st in a du lt s54 a n d t h en in ch ildr en . 55,56 Ou r g r ou p
w a s t h e fir st t o in t r odu ce lon g t er m a dm in ist r a t ion of biosy n t h et ic IGF-1 t o ch ildr en w it h pr im a r y IGF1 deficien cy pr im a r y GH in sen sit iv it y or LS. 57 T h e fin din g t h a t da ily IGF-1 a dm in ist r a t ion r a ises
ser u m a lk a lin e ph osph a t ose, w h ich is a n in dica t or of ost eobla st ic a ct iv it y , a n d ser u m pr ocolla g en , 57,58
in a ddit ion t o IGFBP-3 , 21 led t o lon g t er m t r ea t m en t . T r ea t m en t of pa t ien t s w it h LS w a s a lso in it ia t ed in
ot h er pa r t s of t h e w or ld. 5962 T h e differ en ce bet w een u s a n d t h e ot h er g r ou ps w a s t h a t w e u sed a on ce
da ily dose, w h er ea s t h e ot h er s a dm in ist er ed IGF-1 t w ice da ily . 60 T a ble 1

com pa r es t h e lin ea r g r ow t h

r espon se of ch ildr en w it h LS t r ea t ed by fou r differ en t g r ou ps. It ca n be seen t h a t befor e t r ea t m en t t h e

m ea n g r ow t h v elocit y w a s 3 4 .7 cm /y ea r a n d t h a t t h is in cr ea sed a ft er IGF-1 t r ea t m en t t o 8 .2 9 .1
cm /y ea r , follow ed by a low er v elocit y of 5 .5 6 .4 cm /y ea r in t h e n ex t t w o y ea r s. (In GH t r ea t m en t t h e
h ig h est g r ow t h v elocit y r eg ist er ed is a lso in t h e fir st y ea r of t r ea t m en t .) Fig u r e 5
g r ow t h r espon se t o IGF-1 in eig h t ch ildr en du r in g t h e fir st y ea r s of t r ea t m en t .

65

illu st r a t es t h e

Ra n k e a n d collea g u es60

r epor t ed t h a t t w o of t h eir pa t ien t s h a d r ea ch ed t h e t h ir d cen t ile (T a n n er ), a s did t h e pa t ien t of Kr zisn ik

a n d Ba t t elin o66 ; h ow ev er , m ost pa t ien t s did n ot r ea ch a n or m a l fin a l h eig h t . T h e r ea son s m a y be la t e
in it ia t ion of t r ea t m en t , ir r eg u la r IGF-1 a dm in ist r a t ion , u n der dosa g e, et c. Ra n k e et al con clu de t h a t
lon g t er m t r ea t m en t of pa t ien t s w it h LS pr om ot ed g r ow t h a n d, if t r ea t m en t is st a r t ed a t a n ea r ly a g e,
t h er e is a con sider a ble pot en t ia l for a ch iev in g h eig h t n or m a lisa t ion . 60 Beca u se n o pa t ien t in ou r g r ou p
w a s t r ea t ed sin ce ea r ly in fa n cy t o fin a l h eig h t w e ca n n ot con fir m t h is opin ion .
Fi gur e 5
Gr ow th v el oc i ty b ef or e and dur i ng i nsul i n-l i k e gr ow th f ac tor 1 (IGF-1 ) tr eatment. N ote that i n
i nf anc y , w hen the non-gr ow th hor mone/IGF-1 dependent gr ow th v el oc i ty i s r el ati v el y hi gh (b ut l ow
f or age), the c hange i nduc ed b y IGF-1 admi ni str ati on i s l ess ...

Tab l e 1
Li near gr ow th r esponse of c hi l dr en w i th Lar on sy ndr ome tr eated b y means of i nsul i n-l i k e gr ow th
f ac tor 1 (IGF-1 )

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f ac tor 1 (IGF-1 )

Insulin-like growth factor 1 (IGF-1): a growth hormone

W h en t h e g r ow t h r espon se t o GH t r ea t m en t in in fa n t s w it h IGHD w a s com pa r ed w it h t h a t of IGF-1 in

in fa n t s w it h LS w e fou n d t h a t t h e in fa n t s w it h IGHD r espon ded fa st er a n d bet t er t h a n t h ose w it h LS. 67
How ev er , t h e sm a ll n u m ber of pa t ien t s a n d t h e differ en ces in g r ow t h r et a r da t ion bet w een t h e t w o
g r ou ps m a k es it difficu lt t o r ea ch a con clu sion .
Bot h h or m on es st im u la t ed lin ea r g r ow t h , bu t GH seem ed m or e effect iv e t h a n IGF-1 . On e ca u se m a y be
t h e g r ea t er g r ow t h deficit of t h e in fa n t s w it h LS t h a n t h ose w it h IGHD, a n in su fficien t dose of IGF-1 , or
t h a t t h er e is a n eed for som e GH t o pr ov ide a n a dequ a t e st em cell popu la t ion of pr ech on dr ocy t es t o
en a ble fu ll ex pr ession of t h e g r ow t h pr om ot in g a ct ion of IGF-1 , a s post u la t ed by Gr een a n d collea g u es68
a n d Oh lson et al. 69 A ll t h e a bov e fin din g s ba sed on a few clin ica l st u dies w it h sm a ll g r ou ps of pa t ien t s
a n d a few ex per im en t a l st u dies r em a in a t pr esen t con t r ov er sia l. T h e cr u cia l qu est ion is w h et h er t h er e
a r e a n y , a n d if so, w h et h er t h er e a r e su fficien t IGF-1 r ecept or s in t h e pr og en it or ca r t ila g e zon e of t h e
epiph y sea l ca r t ila g e (fig 4 ) t o r espon d t o en docr in e a n d ex og en ou s IGF-1 . Usin g t h e m a n dibu la r
con dy le of 2 da y old ICR m ice, Ma or et al sh ow ed t h a t t h ese con dy les, w h ich r esem ble t h e epiph y sea l
pla t es of t h e lon g bon es, con t a in IGF-1 a n d h ig h a ffin it y IGF-1 r ecept or s a lso in t h e ch on dr opr og en it or
cell la y er s, w h ich en a bles t h em t o r espon d t o IGF-1 in v it r o. 70
Sim s et al, 71 u sin g m ice w it h GH r ecept or KO sh ow ed t h a t IGF-1 a dm in ist r a t ion st im u la t es t h e g r ow t h
(w idt h ) of t h e t ibia l g r ow t h pla t e a n d t h a t IGF-1 h a s a GH in depen den t effect on t h e g r ow t h pla t e. T h ese
fin din g s a r e sim ila r t o t h ose fou n d w h en t r ea t in g h y poph y sect om ised r a t s w it h IGF-1 . 51,52
In con clu sion , IGF-1 is a n im por t a n t g r ow t h h or m on e, m edia t in g t h e a n a bolic a n d lin ea r g r ow t h
pr om ot in g effect of pit u it a r y GH pr ot ein . It h a s a GH in depen den t g r ow t h st im u la t in g effect , w h ich
w it h r espect t o ca r t ila g e cells is possibly opt im ised by t h e sy n er g ist ic a ct ion w it h GH.

Article information
Mol Pathol. Oct 2001; 54(5): 311316.
PMCID: PMC1187088
Z Laron
Endocrinology and Diabetes Research Unit, WHO Collaborating Center for the Study of Diabetes in Youth, Schneider Children's Medical Center, Tel Aviv
University, 14 Kaplan Street, Petah Tikva 49202, Tel Aviv, Israel
Professor Laron laronz/at/clalit.org.il
Accepted April 24, 2001.
Copyright 2001, Journal of Clinical Pathology
This article has been cited by other articles in PMC.
Articles from Molecular Pathology : MP are provided here courtesy of BMJ Group

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