University of Illinois at Chicago College of Medicine Graduate Education in Medical Sciences Co-Director University of Illinois at Chicago College of Medicine Physiology and Biophysics Associate Professor |  |
QualificationsBiochemistry, Biophysics and G, College of Medicine, Physiology and Biophysics, 1983. Ph.D.. Expertise and Research InterestsRole of inflammation and oxidative stress in the etiology of hormonal carcinogenesis
Prevention and treatment of ovarian cancer with functional food based diets (flax seed) rich in omega-3 fatty acids
Chicken as a model for human disease
Immune-endocrine control of male reproductive function Regulation of steroidogenic enzyme gene expression in Leydig cells
Impact of the environment on reproductive processes Role of oxidative stress in regulation of reproductive function Other ExpertiseMitochondrial biology Adrenal physiology
Future ResearchOur exploration into immune modulation of Leydig cell steroidogenesis revealed that oxidative stress related perturbation of Leydig cell mitochondria mediates the abrupt cessation of testosterone production at the level of cholesterol transfer to the steroidogenic pathway. This mechanism is central to a host of pathologies known to present with hypogonadism including alcoholism, diabetes, aging and certain environmental endocrine disruptors. Our laboratory has initiated studies in oxidative stress effects of alcoholism, diabetes and aging as well as environmental agro and industrial compounds such as dioxin, polycyclic armoatic hydrocarbons, and conazoles.
Industrial RelevanceTherapeutic intervention for workplace exposure to endocrine disruptors that cause decreased testosterone
KeywordsCOS Keywords:Biochemistry, Cytokines, Endocrinology, Gene Expression, Gene Regulation, Inflammation, Molecular Biology, Oxidative Stress, Physiology, Reproductive Endocrinology.Additional Terms:Biochemistry, Cancer, Cytokine, Endocrinology, Inflammation, Leydig Cell, Mitochondria, Molecular Biology, Oxidative Stress, Physiology, Reactive Oxygen Species, Steroidogenesis, Testosterone.MembershipsAmerican Association for the Advancement of Science American Physiological Society American Society for Biochemistry and Molecular Biology American Society for Reproductive Immunology Endocrine Society Mitochondrial Research Society Society for the Study of Reproduction Previous Positions1989-1995, Assistant Professor,
University of Illinois at Chicago,
College of Medicine,
Physiology and Biophysics
Funding Received- United States Department of Defense (DOD):
"CYP1B1, oxidative stress, and inflammation in the etiology of ovarian epithelial cancer using an avian model of ovarian carcinoma,
$300,000,
2005
to 2007.
- American Cancer Society (ACS):
CYP1B1, Oxidative Stress and Prostate Cancer,
100,000,
2004
to 2006.
- National Institutes of Health (NIH):
"Mechanisms of Estrogen Biosynthesis in Endometriosis,
Co-Investigator (Ser,
2004
to 2009.
- NICHD U-54 Director, histology core:
Center for Women's Health and Reproduction,
7,000,000,
2002
to 2007.
Publications- Hauet T, Yao ZX, Bose HS, Wall CT, Han Z, Li W, Hales DB, Miller WL, Culty M, Papadopoulos V (Feb 2005) Peripheral-type benzodiazepine receptor-mediated action of steroidogenic
acute regulatory protein on cholesterol entry into leydig cell
mitochondria., Molecular Endocrinology (baltimore, Md.), 19 (2), 540-54
 - Payne AH, Hales DB (Dec 2004) Overview of steroidogenic enzymes in the pathway from cholesterol to
active steroid hormones., Endocrine Reviews, 25 (6), 947-70
 - Allen JA, Diemer T, Janus P, Hales KH, Hales DB (Dec 2004) Bacterial endotoxin lipopolysaccharide and reactive oxygen species inhibit
Leydig cell steroidogenesis via perturbation of mitochondria., Endocrine, 25 (3), 265-75
 - Fleury A, Mathieu AP, Ducharme L, Hales DB, LeHoux JG (Aug 2004) Phosphorylation and function of the hamster adrenal steroidogenic acute
regulatory protein (StAR)., The Journal of Steroid Biochemistry and Molecular Biology, 91 (4-5), 259-71
 - Selvage DJ, Hales DB, Rivier CL (Mar 2004) Comparison between the influence of the systemic and central injection of
alcohol on Leydig cell activity., Alcoholism, Clinical and Experimental Research, 28 (3), 480-8
 - LeHoux JG, Fleury A, Ducharme L, Hales DB (Feb 2004) Phosphorylation of the hamster adrenal steroidogenic acute regulatory
protein as analyzed by two-dimensional polyacrylamide gel
electrophoreses., Molecular and Cellular Endocrinology, 215 (1-2), 127-34
 - Benmessahel Y, Troadec JD, Cadepond F, Guennoun R, Hales DB, Schumacher M, Groyer G (Feb 2004) Downregulation of steroidogenic acute regulatory protein (StAR) gene
expression by cyclic AMP in cultured Schwann cells., Glia, 45 (3), 213-28
 - Granot Z, Geiss-Friedlander R, Melamed-Book N, Eimerl S, Timberg R, Weiss AM, Hales KH, Hales DB, Stocco DM, Orly J (Dec 2003) Proteolysis of normal and mutated steroidogenic acute regulatory proteins
in the mitochondria: the fate of unwanted proteins., Molecular Endocrinology (baltimore, Md.), 17 (12), 2461-76
 - Sierra A, Lavaque E, Perez-Martin M, Azcoitia I, Hales DB, Garcia-Segura LM (Sep 2003) Steroidogenic acute regulatory protein in the rat brain: cellular
distribution, developmental regulation and overexpression after
injury., The European Journal of Neuroscience, 18 (6), 1458-67
 - Provost AC, Pequignot MO, Sainton KM, Gadin S, Salle S, Marchant D, Hales DB, Abitbol M (Sep 2003) Expression of SR-BI receptor and StAR protein in rat ocular tissues., Comptes Rendus Biologies, 326 (9), 841-51
 - Diemer T, Allen JA, Hales KH, Hales DB (Jul 2003) Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and
inhibits steroidogenic acute regulatory (StAR) protein and
steroidogenesis., Endocrinology, 144 (7), 2882-91
 - Jirawatnotai S, Moons DS, Stocco CO, Franks R, Hales DB, Gibori G, Kiyokawa H (May 2003) The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 cooperate to
restrict proliferative life span in differentiating ovarian
cells., The Journal of Biological Chemistry, 278 (19), 17021-7
 - Diemer T, Hales DB, Weidner W (Feb 2003) Immune-endocrine interactions and Leydig cell function: the role of
cytokines., Andrologia, 35 (1), 55-63
 - Sorianello E, Fritz S, Beyer C, Hales DB, Mayerhofer A, Libertun C, Lux-Lantos V, Development of an experimental ovarian tumor: immunocytochemical analysis, European Journal of Endocrinology / European Federation of Endocrine Societies., 147(3), 387-95, September 2002
 - Salvador LM, Maizels E, Hales DB, Miyamoto E, Yamamoto H, Hunzicker-Dunn M, Acute signaling by the LH receptor is independent of protein kinase C
activation, Endocrinology, 143(8), 2986-94, Aug 2002
 - Hales DB, Another piece in the maddening puzzle of declining steroidogenesis in
aging Leydig cells, Journal of Andrology, 23(3), 327-8; discussion 32, 2002
 - Shea-Eaton W, Sandhoff TW, Lopez D, Hales DB, McLean MP, Transcriptional repression of the rat steroidogenic acute regulatory
(StAR) protein gene by the AP-1 family member c-Fos, Molecular and Cellular Endocrinology, 188(1-2), 161-70, February 2002
 - Moons DS, Jirawatnotai S, Tsutsui T, Franks R, Parlow AF, Hales DB, Gibori G, Fazleabas AT, Kiyokawa H, Intact follicular maturation and defective luteal function in mice
deficient for cyclin- dependent kinase-4, Endocrinology, 143(2), 647-54, February 2002
 - Hales DB (Oct-Nov 2002) Testicular macrophage modulation of Leydig cell steroidogenesis., Journal of Reproductive Immunology, 57 (1-2), 3-18
 - Artemenko IP, Zhao D, Hales DB, Hales KH, Jefcoate CR, Mitochondrial processing of newly synthesized steroidogenic acute
regulatory protein (StAR), but not total StAR, mediates cholesterol
transfer to cytochrome P450 side chain cleavage enzyme, Journal of Biological Chemistry, 276(49), 46583-96, December 2001
 - Wang ZJ, Jeffs B, Ito M, Achermann JC, Yu RN, Hales DB, Jameson JL, Aromatase (Cyp19) expression is up-regulated by targeted disruption of
Dax1, Proceedings of the National Academy of Sciences (USA), 98(14), 7988-93, July 2001
 - Hales DB, Editorial: gonadal-specific transcription factors--gata (go) 4 it!, Endocrinology, 142(3), 974-6, March 2001
 - Fritz S, Grunert R, Stocco DM, Hales DB, Mayerhofer A, StAR protein is increased by muscarinic receptor activation in human
luteinized granulosa cells, Molecular and Cellular Endocrinology, 171(1-2), 49-51, Jan 2001
 - Cascio C, Brown RC, Liu Y, Han Z, Hales DB, Papadopoulos V, Pathways of dehydroepiandrosterone formation in rat brain glia, Journal of Steroid Biochemistry and Molecular Biology, 75(2-3), 177-86, December 2000
 - Hales KH, Diemer T, Ginde S, Shankar BK, Roberts M, Bosmann HB, Hales DB, Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and
Leydig cell steroidogenic acute regulatory protein, Endocrinology, 141(11), 4000-12, November 2000
 - Diemer T, Ludwig M, Huwe P, Hales DB, Weidner W, Influence of urogenital infection on sperm function., Curr Opin Urol, 10(1), 39-44, 2000
 - Lehoux JG, Hales DB, Fleury A, Briere N, Martel D, Ducharme L, The in vivo effects of adrenocorticotropin and sodium restriction on the
formation of the different species of steroidogenic acute regulatory
protein in rat adrenal, Endocrinology, 140(11), 5154-64, November 1999
 - Fiedler EP, Plouffe L Jr, Hales DB, Hales KH, Khan I, Prostaglandin F(2alpha) induces a rapid decline in progesterone production
and steroidogenic acute regulatory protein expression in isolated rat
corpus luteum without altering messenger ri, Biology of Reproduction, 61(3), 643-50, September 1999
 - Hales DB, Diemer T, Hales KH, Role of cytokines in testicular function., Endocrine, 10(3), 201-17, June 1999
 - Sam AD 2nd, Sharma AC, Lee LY, Hales DB, Law WR, Ferguson JL, Bosmann HB, Sepsis produces depression of testosterone and steroidogenic acute regulatory \(StAR\) protein., Shock, 11(4), 298-301, April 1999
 - Sandhoff TW, Hales DB, Hales KH, McLean MP, Transcriptional regulation of the rat steroidogenic acute regulatory
protein gene by steroidogenic factor 1, Endocrinology, 139(12), 4820-31, December 1998
 - Fleury A, Ducharme L, Hales DB, Stocco DM, LeHoux JG, Acute in vivo effects of ACTH on the expression of steroidogenic acute
regulatory protein in rat adrenal, Endocrine Research, 24(3-4), 571-4, 1998
 - Sharma AC, Sam AD 2nd, Lee LY, Hales DB, Law WR, Ferguson JL, Bosmann HB, Effect of NG-nitro-L-arginine methyl ester on testicular blood flow and
serum steroid hormones during sepsis, Shock (augusta, Ga.), 9(6), 416-21, June 1998
 - Hales DB, Greene R, Arginine vasopressin inhibition of cytochrome P450c17 and testosterone
production in mouse Leydig cells, Endocrine, 8(1), 19-28, February 1998
 - Ronen-Fuhrmann T, Timberg R, King SR, Hales KH, Hales DB, Stocco DM, Orly J, Spatio-temporal expression patterns of steroidogenic acute regulatory
protein (StAR) during follicular development in the rat
ovary, Endocrinology, 139(1), 303-15, Jan 1998
 - Xiong Y, Hales DB, Differential effects of tumor necrosis factor-alpha and interleukin-1 on 3
beta-hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase expression
in mouse Leydig cells, Endocrine, 7(3), 295-301, December 1997
 - Clark BJ, Combs R, Hales KH, Hales DB, Stocco DM, Inhibition of transcription affects synthesis of steroidogenic acute
regulatory protein and steroidogenesis in MA-10 mouse Leydig tumor
cells, Endocrinology, 138(11), 4893-901, November 1997
 - Li X, Hales KH, Watanabe G, Lee RJ, Pestell RG, Hales DB, The effect of tumor necrosis factor-alpha and cAMP on induction of AP-1 activity in MA-10 tumor Leydig cells., Endocrine, 6(3), 317-24, 1997
 - Bosmann HB, Hales KH, Li X, Liu Z, Stocco DM, Hales DB, Acute in vivo inhibition of testosterone by endotoxin parallels loss of
steroidogenic acute regulatory (StAR) protein in Leydig
cells, Endocrinology, 137(10), 4522-5, October 1996
 - Sharma AC, Bosmann HB, Motew SJ, Hales KH, Hales DB, Ferguson JL, Steroid hormone alterations following induction of chronic intraperitoneal
sepsis in male rats, Shock (augusta, Ga.), 6(2), 150-4, August 1996
 - McLean MP, Warden KJ, Sandhoff TW, Irby RB, Hales DB, Altered ovarian sterol carrier protein expression in the pregnant
streptozotocin-treated diabetic rat, Biology of Reproduction, 55(1), 38-46, July 1996
 - Naaman-Reperant E, Hales DB, Durand P, Effect of transforming growth factor beta-1 on the cholesterol side-chain
cleavage system in the adrenal gland of sheep fetuses and
newborns, Endocrinology, 137(3), 886-92, March 1996
 - Li X, Youngblood GL, Payne AH, Hales DB, Tumor necrosis factor-alpha inhibition of 17 alpha-hydroxylase/C17-20 lyase gene \(Cyp17\) expression., Endocrinology, 136(8), 3519-26, 1995
 - Xiong Y, Hales DB, Expression, regulation, and production of tumor necrosis factor-alpha in
mouse testicular interstitial macrophages in vitro, Endocrinology, 133(6), 2568-73, December 1993
 - Hales DB, Interleukin-1 inhibits Leydig cell steroidogenesis primarily by decreasing
17 alpha-hydroxylase/C17-20 lyase cytochrome P450 expression, Endocrinology, 131(5), 2165-72, November 1992
 - Durkee TJ, McLean MP, Hales DB, Payne AH, Waterman MR, Khan I, Gibori G, P450(17 alpha) and P450SCC gene expression and regulation in the rat
placenta, Endocrinology, 130(3), 1309-17, March 1992
 - Hales DB, Sha L, Payne AH, Glucocorticoid and cyclic adenosine 3'5'-monophosphate-mediated induction
of cholesterol side-chain cleavage cytochrome P450 (P450scc) in MA-10
tumor Leydig cells. Increases in mRNA are cy, Endocrinology, 126(6), 2800-8, June 1990
 - Hales DB, Payne AH, Glucocorticoid-mediated repression of P450scc mRNA and de novo synthesis
in cultured Leydig cells, Endocrinology, 124(5), 2099-104, May 1989
 - Hales DB, Ho B, Thompson JA, Inter- and intramolecular deuterium isotope effects on the cytochrome
P-450-catalyzed oxidative dehalogenation of 1,1,2,2-tetrachloroethane, Biochemical and Biophysical Research Communications, 149(2), 319-25, December 1987
 - Payne AH, Anakwe OO, Hales DB, Georgiou M, Perkins LM, Quinn PG, Regulation of mitochondrial and microsomal cytochrome P-450 enzymes in
Leydig cells, Advances in Experimental Medicine and Biology, 219, 467-87, 1987
 - Hales DB, Betz G, NADPH-cytochrome P-450 reductase from untreated rat testicular and liver
microsomes: isolation and comparison, Endocrinology, 119(2), 811-8, August 1986
 - Hales DB, Betz G, Steroid interactions with cytochrome P-450 from testis microsomes, Journal of Steroid Biochemistry, 21(6), 639-42, December 1984
 - Betz G, Tsai P, Hales D, Reconstitution of steroid 17,20-lyase activity after separation and
purification of cytochrome P-450 and its reductase from rat testis
microsomes, Endocrinology, 107(4), 1055-60, October 1980

Profile DetailsIndividual Expertise profile of Dale B. Hales, Copyright Dale B. Hales. © COS Expertise TM, 2008, ProQuest LLC All rights reserved. |