THE ROLE OF PROGESTINS, INSULIN-LIKE-GROWTH-FACTOR (IGF) AND IGF-BINDING PROTEINS IN THE NORMAL AND NEOPLASTIC MAMMARY-GLAND OF THE BITCH -A REVIEW

The growth hormone (GH) and insulin-like growth factor (IGF) system is an important regulatory system of mammalian epithelial cell prolifera tion and differentiation. The biological effects of the IGFs are modul ated by six different binding proteins (IGFBPs). Progestins play an im portant role in the regulation of the dynamics of mammary gland develo pment and involution through the modulation of these growth regulating factors. In dogs and cats, progestins stimulate the local production of GH in the mammary gland. In dogs, this results in high plasma conce ntrations of GH and a concomitant increase in plasma IGF-I and IGFBP-3 concentrations. The administration of progestins also induces high pl asma concentrations of IGF-II, even before GH concentrations start to increase. In the mammary gland of the normal bitch, IGFBP-5 and IGFBP- 2 are the main IGFBPs expressed. Progestin administration results in a decrease of mRNA encoding IGFBP-5, but does not alter the concentrati on of mRNA encoding IGFBP-2. This local mammary system of GH, IGFs and IGFBPs plays an important role in the regulation of mammogenesis, lac tation and involution. However, the presence of a high proliferative e nvironment may also enhance the risk of malignant transformation and p romotion of tumour growth with an associated inhibition of programmed cell death.