Ganong's Review of Medical Physiology, 23rd Edition

380
SECTION IV
Endocrine & Reproductive Physiology

above,
α

• and
  β
  -MSH do not circulate in adult humans, and
  their function is unknown. However, ACTH binds to melan-
  otropin-1 receptors. Indeed, the pigmentary changes in sev-
  eral human endocrine diseases are due to changes in
  circulating ACTH. For example, abnormal pallor is a hall-
  mark of hypopituitarism. Hyperpigmentation occurs in
  patients with adrenal insufficiency due to primary adrenal
  disease. Indeed, the presence of hyperpigmentation in associ-
  ation with adrenal insufficiency rules out the possibility that
  the insufficiency is secondary to pituitary or hypothalamic
  disease because in these conditions, plasma ACTH is not
  increased (see Chapter 22). Other disorders of pigmentation
  result from peripheral mechanisms. Thus,
  albinos
  have a con-
  genital inability to synthesize melanin. This can result from a
  variety of different genetic defects in the pathways for mela-
  nin synthesis.
  Piebaldism
  is characterized by patches of skin
  that lack melanin as a result of congenital defects in the
  migration of pigment cell precursors from the neural crest
  during embryonic development. Not only the condition but
  also the precise pattern of the loss is passed from one genera-
  tion to the next.
  Vitiligo
  involves a similar patchy loss of mel-
  anin, but the loss develops progressively after birth secondary
  to an autoimmune process that targets melanocytes.

GROWTH HORMONE

BIOSYNTHESIS & CHEMISTRY

The long arm of human chromosome 17 contains the growth

hormone-hCS cluster that contains five genes: one,

hGH-N,

codes for the most abundant (“normal”) form of growth hor-

mone; a second,

hGH-V,

codes for the variant form of growth

hormone (see below); two code for human chorionic so-

matomammotropin (hCS) (see Chapter 25); and the fifth is

probably an hCS pseudogene.

The structure of hGH-N is shown in Figure 24–3, where it

is also compared with that of hCS. Growth hormone that is

secreted into the circulation by the pituitary gland consists of

a complex mixture of hGH-N, peptides derived from this

molecule with varying degrees of post-translational modifica-

tions, such as glycosylation, and a splice variant of hGH-N

that lacks amino acids 32–46. The physiologic significance of

this complex array of hormones has yet to be fully under-

stood, particularly since their structural similarities make it

difficult to assay for each species separately. Nevertheless,

there is emerging evidence that while the various peptides

share a broad range of functions, they may occasionally exert

actions in opposition to one another. hGH-V and hCS, on the

other hand, are primarily products of the placenta, and as a

FIGURE 24–3
Structure of the principal human growth hormone (continuous chain).
The red bars indicate disulfide bridges. The 29
residues alongside the chain identify residues that differ in human chorionic somatomammotropin (hCS; see Chapter 23). All the other residues in
hCS are the same, and hCS also has 191 amino acid residues.

S S L

V Y

N

V

Q M

R

F L F A N

L

S W

Gin

I L L L S I R L L Q L N S K Q Q T

E E

R

M

N S

P T P I S E S

D

E

E

E P

R

95

V

90

85

80

75

70

65

(^6055)
100
G A
S
N
D
D S
D
D V
Y D L L K D
E E L
H
T
105
110
35
30
20 25
15
10
5
1
115
I G
Q
T
L
120
M
G
R
E L
G D
P S
R
F I Q G T R
Q K
T Y S K F D T N S H N D
H
D A
L L
K N Y G
L L Y C
C L S
T Q
P
S N
D
H
Q
L
F
S
Y
K
Q
E
K
P
I
Y
T A
E
E
F
E
Q
T Y
L A F D
L H Q
A
H R
R A
L M A D F L R S L P I T P
F V
Q
V
Q
N
H
I
D
F
F
F R
K
D
M
D
K
V
E
F T
R L
C Q
V
I
M
S C G F
E G
V
S R
L
125
130
135
140
145
155
160 165
170
50
45
185 180 175 40
150
191
NH 2 COOH