To explore the roles of the lactogens in adipose tissue development and fun
ction, we measured body weight, abdominal fat content, and plasma leptin co
ncentrations in a unique model of lactogen resistance: the PRL receptor (PR
LR)-deficient mouse. The absence of PRLRs in knockout mice was accompanied
by a small (5-12%), but progressive, reduction in body weight after 16 week
s of age. Females were affected to a greater degree than males. The reducti
on in weight in female PRLR-deficient mice (age 8-9 months) was associated
with a 49% reduction in total abdominal fat mass and a 29% reduction in fat
mass expressed as a percentage of body weight. Lesser reductions were note
d in male mice. Plasma leptin concentrations were reduced in females but no
t in males. That the reductions in abdominal fat may reflect in part the ab
sence of lactogen action in the adipocyte is suggested by the demonstration
of PRLR messenger RNA in normal mouse white adipose tissue. Nevertheless,
steady state levels of PRLR messenger RNA in mature adipocytes are very low
, suggesting that the effects of lactogens might be mediated by other hormo
nes or cellular growth factors. Our observations suggest roles for the lact
ogens in adipose tissue growth and metabolism in pregnancy and postnatal li
fe.