Estrogens as regulator of hematopoietic stem cell, immune cells and bone biology

Hematopoietic stem cells provide continuous supply of all the immune cells, through proliferation and differentiation decisions. These decisions are controlled by local bone marrow environment as well as by long-range signals for example endocrine system. Sex dependent differential immunological responses have been described under homeostasis and disease conditions. Females show higher longevity than male counterpart that seems to depend on major female sex hormone, estrogen. There are four estrogens - Estrone (E1), estradiol (E2), Estriol (E3) and Estetrol (E4) that spatially and temporarily present during different female reproductive phases. In this review, we discussed recent updates describing the effects of estrogen on HSC, immune cells and in bone biology. Estradiol (E2) being a major/abundant estrogen is extensively investigated, while effects of other estrogens E1, E3 and E4 are started to unravel recently. Furthermore, clinical effect of estrogen as hormone therapy is discussed in HSC and immune cells perspectives. The data presented in this review is compiled by searches of PubMed, database of American Cancer Society (ACS). We have included article from September 1994 to March 2020 as covering all article in chronological order is not fissile so we included relevant article with substantial information in this specific area of research by using the search term (alone or in combination) estrogen, hematopoietic stem cell, immune cells, gender difference, estrone, estriol, estetrol, therapeutic application, pregnancy, effect on bone.

Automated summary

Hematopoietic stem cells provide a continuous supply of all immune cells through proliferation and differentiation decisions, with these decisions being controlled by the local bone marrow environment and long-range signals. Female longevity seems to depend on the major female sex hormone, estrogen, under homeostasis and disease conditions. Estrogen has effects on HSC, immune cells, and bone biology, with Estradiol (E2) being extensively investigated while the effects of other estrogens such as E1, E3, and E4 are starting to be understood. The clinical effects of estrogen as hormone therapy on HSC and immune cells are also discussed.