HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Catalina, F. Articles by Bennett, M. Search for Related Content PubMed PubMed Citation Articles by Catalina, F. Articles by Bennett, M.

---

ORIGINAL RESEARCH ARTICLE

Dietary Dehydroepiandrosterone Inhibits Bone Marrow and Leukemia Cell Transplants: Role of Food Restriction

Fernando Catalina^*, Leon Milewich, Vinay Kumar^* and Michael Bennett^*,1

^* Departments of Pathology and
Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390–9072

Dietary dehydroepiandrosterone (DHEA) inhibits the proliferation of syngeneic bone marrow cells (BMC) infused into lethally irradiated mice. Potential mechanisms for suppression of hematopoiesis were evaluated and the findings were as follows: (i) depletion of NK, T, B or macrophage cells failed to reverse suppression by DHEA; (ii) stem cell stimulation by erythropoietin, growth hormone, interleukin-2, Friend leukemia virus, or cyclophosphamide failed to reverse suppression; (iii) supplementation of fatty acids, mevalonate, or deoxyribonucleotides, which are dependent upon glucose-6-phosphate dehydrogenase function, did not enhance BMC growth in mice fed DHEA; (iv) DHEA downstream metabolites 4-androstenedione and 17ß-estradiol, as well as the synthetic steroid, 16-chloroepiandrosterone (but not testosterone or 5-androstene-3ß,17ß-diol), also inhibited BMC growth. Tamoxifen antagonized the effects of 17ß-estradiol but not DHEA; (v) dietary DHEA causes hypothermia, but housing of DHEA-fed mice at 34°C to maintain normal body temperature did not reverse suppression; (vi) DHEA leads to a decrease in food intake in rodents. Pair-feeding control diet to mice fed DHEA mimicked the effects of dietary DHEA; (vii) adrenalectomy and orchiectomy decrease the levels of stress and sex hormones, respectively. Neither procedure affected the ability of food restriction or DHEA feeding to inhibit hematopoiesis; (viii) growth of GR-3 NM pre-B leukemia cells in unirradiated mice was also suppressed by DHEA or food restriction. We conclude that DHEA, by reducing food intake in mice, inhibits bone marrow and leukemia cell growth. The precise mechanism(s) by which reduced food intake per se inhibits hematopoiesis is not known, but may involve an increased rate of cellular apoptosis.

Key Words: DHEA • steroids • food restriction • hematopoiesis • leukemia • marrow grafts

This article has been cited by other articles:

				N. Homma, T. Nagaoka, V. Karoor, M. Imamura, L. Taraseviciene-Stewart, L. A. Walker, K. A. Fagan, I. F. McMurtry, and M. Oka Involvement of RhoA/Rho kinase signaling in protection against monocrotaline-induced pulmonary hypertension in pneumonectomized rats by dehydroepiandrosterone Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L71 - L78. [Abstract] [Full Text] [PDF]

				M. Oka, V. Karoor, N. Homma, T. Nagaoka, E. Sakao, S. M. Golembeski, J. Limbird, M. Imamura, S. A. Gebb, K. A. Fagan, et al. Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension Cardiovasc Res, June 1, 2007; 74(3): 377 - 387. [Abstract] [Full Text] [PDF]