Granulosa cells provide nutritional and trophic support for growing oocytes
in ovarian follicles. The granulosa cells closest to the oocyte produce ab
undant insulin-like growth factor 1 (IGF1) and the IGF1 receptor is highly
expressed by oocytes, suggesting that granulosa-derived IGF1 may have troph
ic effects on oocyte growth and development. To investigate this possibilit
y, in the present study we used in situ hybridization and immunohistochemis
try to examine glucose transporter (GLUTs 1, 3 & 4) expression in follicles
from pre-pubertal Igf1-/- and littermate wildtype (wt) mice. Pre-pubertal
mice were used for this study because the Igf1 null mice do not mature sexu
ally. GLUT1 mRNA and immunoreactivity were most abundant in oocytes and in
granulosa cells immediately surrounding the oocyte. Expression of this tran
sporter was significantly reduced in Igf1 null oocytes and granulosa cells
and was restored by exogenous IGF1 treatment to wt levels. These effects on
GLUT expression were significant at both the mRNA and immunoreactive prote
in levels. Oestrogen treatment significantly increased GLUT1 levels in oocy
tes and granulosa from both wt and Igf1-/-, although the latter were still
significantly lower than wt. Oocyte glycogen stores, determined by PAS stai
ning, did not appear different in Igf1-/- and wt mice.
GLUT3 was expressed in thecal cells surrounding growing follicles and was n
ot appreciably different in Igf1 null compared with wt ovaries. GLUT4 expre
ssion was not detected in the prepubertal mouse ovary. Together with observ
ations from previous studies showing that ovulation is blocked in Igf1 null
mice, the present data suggest that IGF1's augmentation of granulosal and
oocyte GLUT1 expression may be essential for oocyte maturation and successf
ul ovulation. (C) 2000 Harcourt Publishers Ltd.