Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enh
ances growth of mice. Growth is attributed to an increase in cell numb
er, due to increased cell proliferation, most obviously in tissues tha
t ordinarily express p27 at the highest levels. Disruption of p27 func
tion leads to nodular hyperplasia in the intermediate lobe of the pitu
itary. However, increased growth occurs without an increase in the amo
unts of either growth hormone or IGF-I. In addition, female mice were
infertile. Luteal cell differentiation is impaired, and a disordered e
strus cycle is detected. These results reflect a disturbance of the hy
pothalamic-pituitary-ovarian axis. The phenotypes of these mice sugges
t that loss of p27 causes an alteration in cell proliferation that can
lead to specific endocrine dysfunction.