Hormones signal through two major mechanisms: via second messengers or direct gene action. since water-soluble hormones (most amino-acid based hormones) cannot enter the target cell directly, they act through plasma membrane receptors and intracellular second messengers. lipid-soluble hormones (steroid and thyroid hormones) can diffuse through the plasma membrane and act on intracellular receptors in the target cells to directly activate genes. watch the a& p flix mechanism of hormone action — second messenger camp video and then complete the activity and question below.