Estrogens play an important role in the regulation of longitudinal bone gro
wth in man, as demonstrated by recent descriptions of individuals with estr
ogen insensitivity or aromatase deficiency. Two estrogen receptors, ER alph
a and ER beta, have been cloned. The aim of the present study was to invest
igate the function of ER alpha in the regulation of body growth and skeleta
l growth. Adult female mice with inactivated ER alpha (ER alpha-/-) demonst
rated an increased body weight compared with wild-type mice (114% of contro
l). However, the length of the appendicular skeleton was decreased in adult
ER alpha-/- mice (femur 93% of control). In contrast, the axial skeleton w
as normal (crown-rump length 98% of control). The decreased growth of the a
ppendicular skeleton was associated with decreased serum levels of IGF-I (7
7% of control), indicating that the GH/IGF-I axis may be involved in the de
creased longitudinal bone growth seen in female ER alpha-/- mice. (C) 1999
Academic Press.