The activity of transcription factor Stat5 responds to prolactin, growth hormone, and IGF-I in rat and bovine mammary explant culture.

Signal transducer and activator of transcription-5 (Stat5) is known to play a critical role in prolactin-induced beta-casein gene transcription in rodents. In nonmammary cells, Stat5 is activated by multiple hormones and cytokines, including growth hormone. We hypothesized that Stat5 may serve as a common point in the signal transduction pathways of hormones that promote milk protein gene expression in bovine mammary cells, which are regulated by GH and IGF-I in addition to prolactin. Assays for Stat5 DNA binding activity and protein were validated in mammary explant culture. The Stat5 protein abundance was not changed by any of the short-term hormonal treatments used in our study, suggesting that short-term regulation of Stat5 is predominantly at the level of protein activation. Both rat and bovine explant culture showed a rapid stimulation of Stat5 DNA binding activity by prolactin, GH, and IGF-I at the high concentrations typically used in explant cultures as well as at levels within physiologic ranges. Growth hormone stimulated Stat5 activity at a lower concentration in bovine than in rat cultures, but in both species the presence of GH increased the response of Stat5 activity to prolactin. These results suggest that transcription factor Stat5 may represent part of a common route by which different extracellular signals converge and are transduced intracellularly to coordinately regulate cell function in the mammary gland.