Uterine Insulin-Like Growth Factor-1: Regulation of Expression and Its Role in Estrogen-Induced Uterine Proliferation*

THE response of the uterus to estrogen is a complexphenomenon involving numerous biochemical events (1). The most dramatic outcome of estrogenization of the immature uterus is the proliferation of various cell types. It is customary to divide the response of the uterus to estrogen into two major temporal phases. In the early phase, within the first 4 h after estrogen administration, there is an increase in uterine wet weight (2), glucose metabolism (3), histamine depletion (4), and RNA polymerase activity (5). One of the early events that is likely to be important in the proliferative response of the uterus to estrogen is activation of protooncogenes which encode nuclear regulatory proteins (6–8) and the enhanced expression of growth factors and their receptors (9) and cAMP-independent protein kinase (10). The intermediate and late phase (4–48 h after estrogen) responses include increases in protein and RNA synthesis and an increase in uterine dry weight and DNA content (11, 12).