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

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2005-05, Vol.113 (5), p.317-323
• Main Authors: ERLANDSSON, M. C., ISLANDER, U., MOVERARE, S., OHLSSON, C., CARLSTEN, H.
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - immunology; Biological and medical sciences; Bone and Bones - drug effects; Bone Density; Bone Marrow - drug effects; bone mineral density; estradiol; Estradiol - agonists; Estrogen Antagonists - pharmacology; Estrogen/agonists/antagonists & inhibitors; Estrogens - agonists; Female; Fundamental and applied biological sciences. Psychology; Genistein; Genistein - pharmacology; Immunoglobulins - metabolism; Infectious diseases; lymphopoiesis; Lymphopoiesis - drug effects; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN OCH HÄLSOVETENSKAP; Mice; Microbiology; Receptors; Receptors, Estrogen - agonists; Receptors, Estrogen - antagonists & inhibitors; Thymus Gland - drug effects; uterus; Uterus - drug effects
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2005.apm_113502.x

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 17β‐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.