INTRODUCTION Prolactin and growth hormone (GH) interact to promote cell survival in the mammary gland in rodents and we proposed that the mechanism involves the insulin-like growth factor (IGF)

Prolactin and growth hormone (GH) interact to promote cell survival in the mammary gland in rodents and we proposed that the mechanism involves the insulin-like growth factor (IGF) system (Flint and Gardner, 1994; Travers et al., 1996; Tonner et al., 1997). GH has been shown to increase insulin-like growth factor-1 (IGF-1) production from mammary stromal cells (Kleinberg et al., 1990) and IGF-1 has in turn been shown to promote mammary epithelial cell survival in transgenic mouse models (Hadsell et al., 1996; Neuenschwander et al., 1996). Prolactin may act by suppressing the production of insulin-like growth factor binding protein-5 (IGFBP-5) from the mammary epithelium. This is based upon the large increase in IGFBP-5 synthesis that occurs during involution of the mammary gland, and the fact that only prolactin was able to markedly suppress this, coincident with an anti-apoptotic effect on the mammary epithelium (Tonner et al., 1997). A number of other studies have added support to this concept. For example, IGFBP-5 expression is reduced and involution delayed in STAT3 KO mice (Chapman et al., 1999) whilst in IRF-1 knockout mice involution and IGFBP-5 expression are both accelerated (Chapman et al., 2000). IGFBP-5 expression is also increased during involution of the prostate and thyroid glands and in ovarian follicles undergoing atresia (Guenette and Tenniswood, 1995; Phillips et al., 1997; Liu et al., 1993). Additional studies of ours and of others have demonstrated extensive expression of IGFBP-5 in the developing embryo, at sites that are consistent with it having a role in apoptosis (van Kleffens et al., 1998). Most striking has been the demonstration 4547 Development 129, 4547-4557 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV1856