Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary.
The present study shows that insulin-like growth factor I (IGF-I) and FSH receptor (FSHR) mRNAs are selectively coexpressed in a subset of healthy-appearing follicles in murine ovaries, irrespective of cycle stage. Aromatase gene expression, a prime marker for FSH effect, is found only in IGF-I/FSHR-positive follicles, showing that these are healthy, gonadotropin-responsive follicles. Given the striking coexpression of FSHR and IGF-I, we hypothesized that FSH was responsible for follicular IGF-I expression. We found, however, that granulosa cell IGF-I mRNA levels are not reduced in hypophysectomized (+/-PMSG) or FSH knockout mice, indicating that FSH does not have a major role in regulation of granulosa cell IGF-I gene expression. To test the alternative hypothesis that IGF-I regulates FSHR gene expression, we studied ovaries from IGF-I knockout mice. FSHR mRNA was significantly reduced in ovaries from homozygous IGF-I knockout compared with wild type mice and was restored to control values by exogenous IGF-I treatment. The functional significance of the reduced FSHR gene expression in IGF-I knockout ovaries is suggested by reduced aromatase expression and by the failure of their follicles to develop normally beyond the early antral stage. In fact, IGF-I knockout and FSH knockout ovaries appear very similar in terms of arrested follicular development. In summary, we have shown that IGF-I and FSHR are selectively coexpressed in healthy, growing murine follicles and that FSH does not affect IGF-I expression but that IGF-I augments granulosa cell FSHR expression. These data suggest that ovarian IGF-I expression serves to enhance granulosa cell FSH responsiveness by augmenting FSHR expression.
Zhou
J
J
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Kumar
T R
TR
Matzuk
M M
MM
Bondy
C
C
D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006062:Gonadotropins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D006062:Gonadotropins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone