Estrogenic agonism and antagonism of the soy isoflavone genistein in uterus, bone and lymphopoiesis in mice

• The isoflavone genistein (Gen) is a naturally occurring phytoestrogen found in high concentrations in soy. The biological effects of Gen have been extensively studied. The immunomodulating properties of Gen are, however, less well investigated and the results are contradictory. Our aim was to study possible estrogen agonistic and antagonistic properties of Gen in uterus, bone, lymphopoiesis and B-cell function by comparing effects in castrated and intact female mice, respectively. Oophorectomized (OVX) and sham-operated mice were treated with s.c. doses of 17beta-estradiol (E2) (0.16 mg/kg), Gen (50 mg/kg), or vehicle (olive oil) as control. Effects on bone mineral density (BMD) were studied using peripheral quantitative computerized tomography, uterine and thymus weights were examined, lymphopoiesis in thymus and bone marrow was analyzed using flow cytometry, and the frequency of immunoglobulin-producing B cells in bone marrow and spleen was studied using an ELISPOT assay. Gen was clearly antagonizing endogenous estrogen in sham-operated female mice as shown by inhibiting the uterine weight and by increasing the frequency of B lymphopoietic cells in bone marrow. The only agonistic effect of Gen was shown by increased BMD in OVX mice. Our results are discussed in the context of estrogen receptor biology.

Nyckelord

Animals

B-Lymphocytes/immunology

Bone Density

Bone Marrow/drug effects

Bone and Bones/*drug effects

Estradiol/agonists

Estrogen Antagonists/*pharmacology

Estrogens/*agonists

Female

Genistein/*pharmacology

Immunoglobulins/metabolism

Lymphopoiesis/*drug effects

Mice

Receptors

Estrogen/agonists/antagonists & inhibitors

Thymus Gland/drug effects

Uterus/*drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)