The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis.
Several observations suggest that sex steroids might participate in steady state regulation of B lymphopoiesis. B cell precursors decline dramatically in bone marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell populations are increased in hypogonadal mice or male castrates. Estrogen treatment of hypogonadal mice reduced precursors to normal. However, questions remain about which hormones and receptors are the most important. Furthermore, these observations need to be reconciled with advances regarding new sex steroid receptors. We have now characterized B lymphopoiesis in androgen receptor-deficient testicular feminization (Tfm) mice. Testicular feminization mice had substantially elevated numbers of B cell precursors in the bone marrow and B cells in the spleen as compared with wild-type mice. The importance of one estrogen receptor (ER alpha) was evaluated in gene-targeted mice, and B cell precursors were found to be within the normal range. Our previous studies indicated that hormone receptors in stromal cells may be important for estrogen-mediated suppression of B lymphopoiesis. We now show that estrogen-mediated inhibition of B cell precursor expansion in culture was blocked by a specific estrogen receptor antagonist (ICI 182,780). Stromal cells derived from ER alpha-targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these stromal cells revealed splice-variant transcripts of ER alpha, as well as message for a recently discovered estrogen-binding receptor, ER beta. Thus, androgens may normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens might utilize one or more receptors to achieve the same physiologic response.
Smithson
G
G
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Couse
J F
JF
Lubahn
D B
DB
Korach
K S
KS
Kincade
P W
PW
D013734:Androgen-Insensitivity Syndrome / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen