ticularly of the gastrointestinal tract, 
than formula-fed babies. 
Hormones, the body’s chemical mes- 
sengers, are other kinds of molecules 
present in milk. Most hormones are ei- 
ther proteins (insulin, for example) 
composed of many amino acids or have 
chemical structures related to steroids. 
A characteristic of all hormones is that 
they are present in body fluids in ex- 
ceedingly small quantities compared 
with other components. Nevertheless, 
hormones play a vital role in regulating 
body chemistry and physiology. For in- 
stance, an individual can ingest large 
amounts of carbohydrates but unless 
insulin is present the carbohydrates will 
not be utilized properly. Similarly, oth- 
er hormones control virtually all proc- 
esses that the body carries out. There 
are a number of hormones known to be 
present in human milk, but their signifi- 
cance has not been demonstrated. This 
does not mean these molecules have no 
significance; it simply means that none 
is yet understood. 
Also present in milk is an interesting 
class of hormones — often referred to as 
growth factors — that controls cell 
growth and differentiation. Research in 
this area is relatively new and it is very 
likely that many more growth factors 
will be identified in the future. Of those 
now known, one of the most thorough- 
ly investigated is epidermal growth fac- 
tor, or EGF. Epidermal growth factor 
is a small protein molecule composed of 
fifty-three amino acid residues. Discov- 
ered in the early 1960s in mice by Stan- 
ley Cohen, a biochemist at Vanderbilt 
University, this hormone has since been 
detected in many mammalian species. 
It is present in almost all human body 
fluids, including milk, where its con- 
centration (approximately thirty nano- 
grams per milliliter) is quite significant 
for a hormone. 
The classic procedure for determin- 
ing the function of a hormone has been 
to surgically remove the hormone-pro- 
ducing organ and record the resultant 
effects of the hormone deficit. The ob- 
served effects can be attributed to the 
hormone deficit if the effects are pre- 
vented or reversed by injection of the 
hormone into the animal. This experi- 
mental strategy is not always possible, 
however. In the case of EGF, it is not 
known w(iere in the body the hormone 
is produced, and the available evidence 
suggests that there are probably several 
distinct sites. Therefore, it has not been 
possible to determine unequivocally 
what functions EGF serves. There are 
experiments, however, that demon- 
strate quite interesting biological 
effects when EGF is administered to 
animals. These results probably pro- 
vide good clues to the natural function 
of this hormone. 
Cohen’s pioneering studies demon- 
strated that EGF had a pronounced 
stimulatory effect on the growth and 
differentiation of the outermost layer of 
the body, the epidermis of the skin — 
hence the name epidermal growth fac- 
tor. In those initial experiments, new- 
born mice were injected daily with 
small quantities of EGF, and an in- 
triguing result was observed. Normal- 
ly, a newborn mouse is born with its 
eyelids shut and, without exception, its 
eyelids open at thirteen to fourteen days 
after birth. But baby mice injected with 
the epidermal growth factor opened 
their eyelids in seven days. The prolif- 
eration of skin cells in the eyelid area 
and their differentiation, a process 
called keratinization, had been acceler- 
ated. Later studies have demonstrated 
that the effect was not limited to the 
eyelid area; all areas of the epidermis 
were similarly stimulated to proliferate 
and keratinize in newborn animals 
treated with EGF. 
More recent experiments have 
shown that EGF stimulates epithelial 
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tissues other than the skin. The entire 
gastrointestinal tract is lined with epi- 
thelial tissue, and several studies have 
shown that EGF stimulates cell divi- 
sion and accelerates certain differenti- 
ation events in this tissue. During 
development in the perinatal period, 
the cells of the gastrointestinal tract be- 
gin to produce hydrolytic enzymes — 
protein molecules required for the di- 
gestion of food. The rates of activity of 
these enzymes are generally low at 
birth and increase as the infant ma- 
tures. If these digestive enzymes do not 
develop at the correct time, the infant is 
less able to utilize food to sustain its nu- 
tritional requirements, and obviously, a 
long delay in the maturation of the di- 
gestive enzymes has serious conse- 
quences. A recent study by a Canadian 
group at the University of Sherbrooke 
in Quebec reports that when newborn 
mice are injected with EGF the matu- 
ration of several digestive enzymes is 
accelerated. Thus the hormone may 
have a significant function in the 
growth and development of this impor- 
tant system. 
A second critical transition for the 
newborn infant occurs at birth, when 
maternal oxygen, which was delivered 
in utero, is no longer available; sud- 
denly oxygen must be taken in from the 
air and, via the lungs and circulatory 
system, made available to the tissues. 
Failure to adjust successfully to atmo- 
spheric oxygen at birth creates a respi- 
ratory distress syndrome called hyaline 
membrane disease. This is, of course, a 
serious condition, and one that is seen 
not infrequently in the baby born pre- 
maturely. The premature infant is es- 
pecially vulnerable to this problem 
because the final stages of lung matura- 
tion in the fetus normally occur just pri- 
or to full-term birth. Hyaline mem- 
brane disease cannot be predicted 
before birth, and the mortality rate is 
low but significant. 
This respiratory syndrome has been 
studied in newborn lambs, and the re- 
sults show that in cases where pregnant 
ewes are subjected to stress and their 
lambs delivered prematurely, many of 
the lambs (75 percent) die soon after 
birth of respiratory distress similar to 
the hyaline membrane disease seen in 
human infants. When the fetal lambs 
are infused in utero with EGF for a few 
days prior to premature delivery, how- 
ever, development of the lung epithe- 
liums is accelerated, respiratory dis- 
tress is infrequent, and almost all of the 
lambs survive. Moreover, in these same 
experiments, accelerated growth of epi- 
12 
