Interactions of prolactin and growth hormone (GH) in the regulation of mammary gland function and epithelial cell survival.

The relative importance of GH and prolactin in mammary gland function varies between species with prolactin playing a major role in rodents and GH taking lead role in ruminants. In rodents, however, GH appears to play a vital role in maintaining a high-fat/low volume milk in the absence of prolactin and a similar finding has been demonstrated in goats where prolactin deficiency causes a more modest (15%) decrease in milk yield. Surprisingly GH-deficiency in goats induced no further decline in milk yield whereas exogenous GH or prolactin both stimulated milk output considerably. Although direct effects of prolactin on mammary epithelial cells are well-documented effects of GH are believed to be mediated indirectly via IGF-1 production from the liver. We have been unable to confirm this hypothesis in rats and believe this to be because it is too simplistic. By considering prolactin and GH to be survival factors for the mammary gland we now propose a mechanism by which they interact through the IGF system. Involution of the mammary gland involves apoptosis and, in rats, it is induced by prolactin-deficiency or milk accumulation. Coincidentally with this process mammary epithelial cells synthesize and secrete and IGF binding protein, IGFBP-5. We hypothesize that GH stimulates IGF-1 production, possibly from the mammary parenchyma. IGF-1 then acts as a survival factor for the mammary gland. Prolactin plays an essential role since it suppresses the secretion of IGFBP-5 which would otherwise inhibit IGF-1 action and lead to the induction of cell death.