SEX STEROID REGULATION OF INSULIN-LIKE GROWTH-FACTOR SYSTEM GENE-EXPRESSION AND PROLIFERATION IN PRIMATE MYOMETRIUM

To investigate the role of locally produced insulin-like growth factor s (IGFs) in sex steroid-induced growth in the primate uterus, ovariect omized rhesus monkeys were treated with placebo (control), estradiol ( E(2)) alone, or E(2) plus progesterone (P-4). After 2 weeks, uteri wer e removed, and serial thin uterine sections were analyzed by in situ h ybridization for IGF-I, IGF-II, and IGF-I and -II receptor messenger r ibonucleic acids (mRNAs) and by immunocytochemistry for the cell proli feration-specific antigen Ki-67. IGF-I and IGF-II and both IGF recepto r mRNAs are coexpressed by smooth muscle cells, supporting the possibi lity of autocrine/paracrine IGF action in stimulating myometrial growt h. IGF-I mRNA is barely detected in control myometrium, is significant ly increased by E(2) treatment, and is augmented even more by the comb ination of E(2) and P-4 treatment, whereas little change is noted in m yometrial IGF-II or IGF-I receptor mRNA levels. Ki-67-positive myometr ial nuclei are also significantly increased by E(2) and are augmented even more by E(4) plus P-4 treatment, with a correlation between local IGF-I mRNA concentration and local Ki-67-positive cell count of r = 0 .891 (P = 0.003). These data provide direct experimental evidence for regulation of IGF-I gene expression by sex steroids in the primate ute rus in vivo and implicate local IGF-I action in both estrogen- and P-4 -induced myometrial growth.