section 31.2

Pituitary Gland (Hypophysis)

741

F I G U R E 3 1 - 6

Structure of hum an prolactin. [Reproduced w ith perm ission from R. K. M urray, D. K. Granner, R A. M ayes, and

V. W. Rodw ell,

H a r p e r ’s B io ch em istry,

21st ed. Norwalk: A ppleton & Lange, 1988. © 1 9 8 8 A ppleton & Lange.]

GH production or responsiveness. Thus, a GH deficiency

results in IGF-I deficiency, whereas a GH excess results in

IGF-I excess. GH deficiency in children results in reduced

growth velocity and growth retardation (dwarfism) due to

secondary IGF-I deficiency, whereas in adults there are no

dramatic signs or symptoms. Adults who are deficient pri-

marily in GH have decreased lean body mass, increased

adiposity, and are at increased risk of cardiovascular

disease.

GH hypersecretion in children causes increased growth

rate and can result in

gigantism.

However, GH excess

occurs infrequently in childhood, and most frequently

in middle-aged adulthood, which leads to

acromegaly

{acral

= extremities +

megas

= large), a condition in

which the cartilaginous tissues proliferate, resulting in

distorted overgrowth of the hands, feet, mandibles, nose,

brow, and cheek bones. Because epiphyseal cartilage is ab-

sent in long bones, there is no gain in height. Acromegaly

promotes insulin resistance and cardiovascular complica-

tions. Resistance to the effects of GH results in a condition

similar to GH deficiency. The major cause of GH resis-

tance is a genetic defect in the growth hormone receptor

(GHR) and the resultant condition is known as

Laron-type

dwarfism.

This is an autosomal recessive disorder char-

acterized by normal to high levels of serum growth hor-

mone and low levels of IGF-I. Analysis of the GHR gene

in Laron-type dwarfism has shown point mutations, dele-

tions, and splicing defects.

Growth hormone deficiency in children can be treated

by administration of recombinant GH or, in some cases,

growth hormone-releasing hormone. Potential targets for

recombinant GH that are undergoing clinical investiga-

tion include children with idiopathic short stature, persons

with wasting syndrome associated with human immunod-

eficiency virus infection, critically ill patients, and elderly

individuals.

Excess production of GH due to somatotroph adeno-

mas may be treated by surgical resection, irradiation, or in

some cases with somatostatin analogues (e.g., octreotide)

that suppress GH secretion, or by a combination of these

above.

Prolactin

Human prolactin (PRL) contains 199 amino acid residues

(M.W. 23,500) and three intramolecular disulfide bridges

(Figure 31-6). In healthy adults the anterior pituitary re-

leases very little PRL under nonstressed conditions, pri-

marily because PRL release is under hypothalamic inhibi-

tion. This inhibition is exerted by dopamine or PIH. The

hypothalamus also secretes PRF but the major regulator

appears to be PIH.