The mammary gland is a dynamic organ with complex paracrine signaling downstream of hormone signaling. A history of pregnancy is protective against breast cancer over a lifetime, but this effect is strongest for an early first full birth. I have created a human breast tissue bank with human donor samples from breast reduction surgeries to study the effect of pregnancy on the breast tissue. A single-cell transcriptomic dataset and matched single-nucleus ATAC dataset were generated to describe the changes in the cell state and cell-cell signaling due to parity. The hormone receptor-positive luminal cells play a central role in the response to hormone signaling, and the degree of response is correlated with age and parity. Increasing age decreases the response to hormones, and parity modifies this relationship to suppress hormone response at the younger age. Cell-cell communications between different cell types are also suppressed in the parous mammary gland. There is a significant signature of interferon response the transcriptional state and accessible chromatin sites of the parous hormone receptor- positive luminal cells, as well as a broad inflammatory signal. These findings suggest a potential interaction of interferon response and hormone signaling in the parous breast. Finally, I generated a single-cell transcriptomics dataset to study the effects of testosterone replacement therapy on the breast tissue of transgender men, and found that testosterone suppresses estrogen signaling in these individuals, and thus potentially provides a protective effect against breast cancer.