Figure 8.

Model predicting critical regulators of secretory activation in the mammary gland. The transcription of milk protein genes is induced by the binding of prolactin to its receptor (the PRLR) and regulated by the STAT5 and ELF5 transcription factors. Translation of milk protein genes may be enhanced by Akt1 acting on their substrates, such as glycogen synthase kinse (GSK)-3/eIF2B, mammalian target of rapamycin (mTOR)/S6 kinase and mTOR/4E-BP1. Transcription of glucose transporter (GLUT)1 may be induced by the PRLR and Akt1 may contribute to either the expression or localization of GLUT1. The response of the mammary gland to dietary fat is sensed by sterol regulatory element binding protein (SREBP), and the stability of SREBP may be enhanced by Akt1-mediated inhibition of GSK3, since phosphorylation of SREBP by GSK3 enhances the ubiquitination and degradation of SREBP in the nucleus.