Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 24

The Pituitary Gland 383

chains are not separated (Figure 24–5) and they have an
extension of the A chain called the D domain. The hormone
relaxin (see Chapter 25) is also a member of this family.
Humans have two related relaxin isoforms, and both resemble
IGF-II. In humans a variant form of IGF-I lacking three
amino terminal amino acid residues has been found in the
brain, and there are several variant forms of human IGF-II
(Figure 24–5). The mRNAs for IGF-I and IGF-II are found in
the liver, in cartilage, and in many other tissues, indicating
that they are synthesized in these tissues.

The properties of IGF-I, IGF-II, and insulin are compared in

Table 24–2. Both are tightly bound to proteins in the plasma,

and, at least for IGF-I, this prolongs their half-life in the circu-

lation. Six different IGF-binding proteins, with different pat-

terns of distribution in various tissues, have been identified.

All are present in plasma, with IGF-binding protein-3 (IGFBP-

3) accounting for 95% of the binding in the circulation. The

contribution of the IGFs to the insulin-like activity in blood is

discussed in Chapter 21. The IGF-I receptor is very similar to

the insulin receptor and probably uses similar or identical

intracellular signaling pathways. The IGF-II receptor has a

FIGURE 24-5
Structure of human IGF-I, IGF-II, and insulin (ins) (top).
The lower panel shows the structure of human IGF-II with its disul-
fide bonds, as well as three variant structures shown: a 21-aa extension of the c-terminus, a tetrapeptide substitution at Ser-29, and a tripeptide
substitution of Ser-33.

GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA

AYRPSETLCGGELVDTLQFVCGDRGFYFSRPA--SRVSRRSR--GIVEECCFRSCDLALLETYCAT--PAKSE

FVNQHLCGSHLVEALYLVCGERGFFYTPKT GIVEQCCTSICSLYQLENYCN

hlGF-I

hlGF-II

h ins

IIIIIIII

BCAD

C

C

C

G

C

D

C

E

E

E

L

L

P

P P

P

L

A

A

A

A

A

K

(^211) ES
T T
V
I
T
Y
Y
C
Q
C
G
G
G
G
G
G
E
E
S
S S
S
R
R R
R
R
R
R
R
S
Y
L
L
V L
V
V
D
D
D
T
L
F
F
F
F
R
S
TABLE 24–2
Comparison of insulin and the insulin-like growth factors.
Insulin IGF-I IGF-II
Other names ... Somatomedin C Multiplication-stimulating activity (MSA)
Number of amino acids 51 70 67
Source Pancreatic B cells Liver and other tissues Diverse tissues
Level regulated by Glucose Growth hormone after birth, nutritional status Unknown
Plasma levels 0.3–2 ng/mL 10–700 ng/mL; peaks at puberty 300–800 ng/mL
Plasma-binding proteins No Yes Yes
Major physiologic role Control of metabolism Skeletal and cartilage growth Growth during fetal development