Testosterone and estrogen are lipid-soluble signal molecules that cross the plasma membrane by simple diffusion. If these molecules can enter all cells, why do only specific cells respond to their presence?

Non - targeted cell lacks intracellular receptor for these hormone.

Explanation:

Receptors that are found on the cell surface are called cell surface receptor and those which are found inside the cell are called intracellular receptors. Intracellular receptor binds to lipophilic molecules. Each receptor binds specifically to a particular ligand or signal molecule.

So even though testosterone and estrogen can diffuse in every cell they will only affect those cell which have specific receptor which can bind to these hormones and then regulate the transcription of a specific gene in the nucleus.

So only those cells will respond to testosterone and estrogen who have specific intracellular receptors for them.