Mice homozygous for targeted disruption of the GH receptor/GH binding prote
in gene (GH-R-KO mice; -/-) exhibit reduced plasma IGF-I levels, elevated p
lasma GH levels, and dwarf phenotype. Although most GH-R-KO mice are fertil
e, age at first conception is greatly delayed in -/- x -/- matings. Here we
report that the age of vaginal opening is significantly delayed in GH-R-KO
vs. normal mice, but it can Se advanced by treatment with recombinant huma
n (rh)IGF-I. In pregnant GH-R-KO females, fetal size is reduced and pregnan
cy is prolonged while placental weight is, unexpectedly, increased. Alterat
ions in fetal and placental weight are related to maternal rather than feta
l genotype. Moreover, litter size and body weight of newborn pups are signi
ficantly reduced in GH-R-KO vs. normal females. Reduction in litter size re
flects both dam and sire effects. We conclude that GH resistance and conseq
uent reduction in peripheral IGF-I levels is associated with delay of femal
e puberty, alterations in fetal and placental growth, delay of parturition,
and reduced litter size.