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 proliferation and differentiation. The biological effects of the IGFs are modulated by six different binding proteins (IGFBPs). Progestins play an important role in the regulation of the dynamics of mammary gland development 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 concentrations of GH and a concomitant increase in plasma IGF-I and IGFBP-3 concentrations. The administration of progestins also induces high plasma 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 concentration of mRNA encoding IGFBP-2. This local mammary system of GH, IGFs and IGFBPs plays an important role in the regulation of mammogenesis, lactation and involution. However, the presence of a high proliferative environment may also enhance the risk of malignant transformation and promotion of tumour growth with an associated inhibition of programmed cell death.