A water-soluble hormone will first interact with a receptor on the surface of the target cell, initiating signal transduction through a second messenger without directly entering the nucleus or interacting with DNA.
When a water-soluble hormone approaches its target cell, the first event that will happen is that the hormone's signal will interact with a receptor located on the surface of the target cell. This hormone-receptor interaction triggers a signaling cascade that's known as signal transduction. During signal transduction, a second messenger within the cytoplasm - typically a molecule like cyclic AMP (cAMP) - will relay the signal from the cell membrane to various intracellular targets, eventually leading to the cellular response.
At this initial point, the hormone's signal does not enter the nucleus nor interact with the cell's DNA directly; instead, it indirectly exerts its effects through these intermediaries. Importantly, because the hormone is water-soluble, it cannot cross the hydrophobic plasma membrane on its own.