Chemoprevention by dietary dehydroepiandrosterone (DHEA): inhibition of lymphopoiesis.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Chemoprevention by dietary dehydroepiandrosterone (DHEA): inhibition of lymphopoiesis.

Diss Abstr Int [B]; 52(9):4660 1992. Unique Identifier : AIDSLINE ICDB/93682331
Risdon GH; Univ. of Texas Health Science Center at Dallas

Abstract: DHEA, a C-19 steroid, is one of the major secretory products of the human adrenal gland. Low levels of DHEA-sulfate have been correlated with both the risk and presence of breast cancer in women and cardiovascular disease in men. In rodents, the ingestion of DHEA inhibits the development of neoplasia, diabetes, obesity and autoimmune diseases. The efficacy of dietary DHEA in murine autoimmunity led us to investigate the potential effects of DHEA upon the immune system. Although dietary DHEA (0.45% w/w) had no effect on cellular or humoral immunity, as much as a 50% reduction in the cellularity of spleen, thymus and lymph nodes from DHEA-fed mice was observed. Histological analysis of spleens revealed a decrease in the ratio of splenic white pulp to red pulp. The splenic white pulp is comprised primarily of lymphocytes, while the red pulp consists of erythrocytes and granulocytes. Since most agents which diminish lymphocyte numbers typically decrease the number of mature lymphocytes, such a decrease in lymphoid organ cellularity without a concomitant effect upon the immune response could result from an inhibition of the generation of mature lymphocytes from their precursor. To address this hypothesis, mice fed DHEA or not were sublethally irradiated. Sublethal irradiation eliminates the majority of hemopoietic cells, sparing the less-differentiated precursors which respond by repopulating the hemopoietic system. Examination of the kinetics of myeloid and lymphoid repopulation demonstrated that DHEA inhibited T-, B- and NK-cell differentiation without affecting the regeneration of granulocytic or erythroid lineage cells. The mechanism of this selective inhibition of lymphocyte differentiation is still under investigation. It appears that DHEA may inhibit lymphopoiesis by regulating the release of the anterior pituitary hormone, prolactin. Furthermore, this inhibition appears to be mediated by a direct affect of DHEA, since an analog of DHEA which cannot be metabolized is also effective at inhibiting lymphopoiesis. The efficacy of dietary DHEA in a murine model of the acquired immunodeficiency syndrome (AIDS) was also examined. The pathogenesis of this murine AIDS is similar to that of human AIDS, resulting in abnormal T- and B-cell function, polyclonal B-cell proliferation and a lymphoproliferative disease which causes splenomegaly and lymphadenopathy. DHEA was found to slow the development of the lymphoproliferative disease in infected mice, even when DHEA feeding was initiated 2 wk after inoculation with the virus.

Keywords: Acquired Immunodeficiency Syndrome Animal Autoimmune Diseases/CHEMICALLY INDUCED B-Lymphocytes/DRUG EFFECTS/PATHOLOGY Breast Neoplasms/*METABOLISM Cardiovascular Diseases/*METABOLISM Cell Differentiation Erythrocytes/PATHOLOGY Female Granulocytes/PATHOLOGY Hematopoietic System/DRUG EFFECTS Human Killer Cells, Natural/DRUG EFFECTS/PATHOLOGY Leukocyte Count Lymph Nodes/DRUG EFFECTS/PATHOLOGY Lymphocytes/PATHOLOGY Lymphoproliferative Disorders/DRUG THERAPY Male Mice Obesity/CHEMICALLY INDUCED Prasterone/ADVERSE EFFECTS/*PHARMACOLOGY/THERAPEUTIC USE Prolactin/ANALYSIS Spleen/DRUG EFFECTS/PATHOLOGY T-Lymphocytes/DRUG EFFECTS/PATHOLOGY THESIS
930530
M9350992

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1993. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1993. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .