T. Roskams et Vj. Desmet, PARATHYROID HORMONE-RELATED PEPTIDE AND DEVELOPMENT OF INTRAHEPATIC BILE-DUCTS IN MAN, HEPATOLOGY RESEARCH, 2(3), 1994, pp. 121-127
Parathyroid hormone-related peptide (PTHrP) is the product of a growth
factor-regulated gene that may play a role in cell growth and differe
ntiation. Previous studies have shown a widespread, yet clearly locali
zed, distribution in embryonic and fetal tissues. These findings are c
onsistent with a paracrine or autocrine function of PTHrP which itself
appears related to the transforming growth factor-beta family of grow
th factors. Recently we found that reactive human bile ductules in chr
onic cholestatic conditions and in regenerating human liver express im
munoreactive PTHrP, while normal adult human liver does not express th
is peptide. Because reactive bile ductules are thought to derive at le
ast in part from 'facultative stem cells', the aim of this study was t
o investigate PTHrP immunoreactivity in human liver during fetal life
and after birth. Therefore, we investigated the distribution of PTHrP
in 12 human fetal liver specimens from 16 weeks of gestation until bir
th, 21 liver specimens from children from 1 day of age to 14 years of
age and four normal adult liver biopsies. These specimens were partly
needle biopsies, taken for diagnostic purposes, partly post mortem spe
cimens. In fetal livers, we found that PTHrP was faintly expressed in
the ductal plate, whereas bile ducts already incorporated in the mesen
chyme of the portal tract showed stronger immunoreactivity. PTHrP immu
noreactivity became more intense with gestational age, and bile ducts
in neonatal livers showed strong immunoreactivity. In children from th
e age of 2-3 years old, PTHrP immunoreactivity progressively diminishe
d and was no longer found after the age of 4 years. All adult biopsies
were consistently negative for PTHrP. These results suggest that PTHr
P plays a physiological role during normal human liver development and
that this peptide may function as a growth and differentiation factor
for growing and maturing bile ducts.