The first indication that the receptors for some hormones are located inside target cells came from studying the vertebrate hormones estrogen and progesterone which are necessary for the normal development and function of the female reproductive system hormones.

The chemical signal of hormones activates the receptor, which then directly triggers the target cell's response by way of a change in gene expression.

Intracellular receptors located in the nucleus bind hormone molecules, which have diffused in from the bloodstream. The resulting hormone – receptor complexes bind, in turn, to specific sites in the cell's DNA and stimulate the transcription of specific genes.

Some steroid hormone receptors, however, are trapped in the cytoplasm and binding of a steroid hormone to its cytoplasmic receptor forms a hormone – receptor complex that can move into the nucleus to stimulate transcription of specific genes. mRNA produced in response to hormone stimulation is translated into new protein in the cytoplasm.