Insulin-like growth factor 1 is required for G(2) progression in the estradiol-induced mitotic cycle

Insulin-like growth factor 1 (IGF1) has been proposed as a "G(1)-progressio n factor" and as a mediator of estradiol's (E2) mitogenic effects on the ut erus. To test these hypotheses, we compared E2's mitogenic effects on the u teri of Igf1-targeted gene deletion (null) and wild-type littermate mice. T he proportion of uterine cells involved in the cell cycle and G(1)- and S-p hase kinetics were not significantly different in wild-type and Igf1-null m ice. However, the appearance of E2-induced mitotic figures and cell number increases were profoundly retarded in Igf1-null uterine tissue. There was a significant increase in nuclear DNA concentration in Igf1-null cells, cons istent with a G(2) arrest. Interestingly, apoptotic cells were also signifi cantly reduced in abundance, and the normal massive apoptotic response to E 2 withdrawal was absent in the Igf1-null uterus. These data show that Igf1 is an essential mediator of E2's mitogenic effects, with a critical role no t in G(1) progression but in G(2) progression.