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Gail S. Prins, Ph.D.Gail S. Prins, Ph.D
Professor of Physiology
Department of Urology
Department of Physiology and Biophysics
University of Illinois at Chicago

 

 

 



Research Interests

My research interests concern basic and applied studies in male reproductive function. My basic research interest involves studies on the prostate gland with an emphasis on hormonal control of prostatic development, growth and function. A major research focus in this field is elucidation of the hormonal regulation of prostate gland steroid receptor expression and the interrelationship between this regulation and the normal and pathological growth, development and secretory function of the prostate gland. The rat is our animal model since its prostate consists of three distinct lobes which serve as a model for tissue heterogeneity, a hallmark of the human prostate gland. My work has described the ontogeny and adult expression patterns of androgen receptors, estrogen receptors (a and ), retinoic acid receptors (a, , g) and progesterone receptor in the separate prostate lobes using binding studies, immunocytochemistry, in situ hybridization, Western and Northern analysis and RT-PCR. We have determined that each of these steroid receptors has distinct localization in specific cell types within the prostate gland and, in addition, unique developmental profiles in the three prostate lobes. Importantly, they are differentially regulated by hormones which leads to complexity in response to the hormonal milieu. Autoregulation of androgen receptor as well as regulation by estrogens is being studied at the molecular level and our findings indicate a posttranscriptional mechanism of control through targeted proteolysis involving the ubiquitin-proteosome pathway.

Another major research interest of my laboratory concerns the effects of neonatal exposure to estrogens on the rodent prostate gland (estrogen imprinting or Developmental Estrogenization). The rat and mouse prostate undergoes morphogenesis after birth and this process can be imprinted by brief exposure to endogenous and exogenous hormones. We have demonstrated that neonatal estrogen exposure permanently imprints prostatic development and is associated with an increased incidence of hyperplasia, dysplasia and adenocarcinoma with aging. Thus, neonatal estrogenization of the rat has evolved as a useful model to evaluate the role of exogenous and endogenous estrogens as a predisposing factor for prostatic diseases later in life. The overall objective of our research in this area is to elucidate the cellular and molecular mechanisms by which fetal and neonatal estrogens initially imprint or transform the prostate gland. Our recent studies have shown that paracrine signaling (e.g.TGF pathways)  between stromal and epithelial cell compartments in the developing prostate as well as epithelial cell communication (gap junctions and cadherin molecules) are disrupted by estrogens leading directly to growth and differentiation defects. We have also determined that key members of the steroid receptor superfamily (namely AR, ERa, ERß, PR and RAR a and ß) are expressed in a cell-specific manner during prostate development and that these expression patterns are markedly altered by early estrogenic exposure. Recent studies with ERa knockout mice and ERKO mice demonstrate that the effects of estrogens are initially mediated through amplification of ERa within stromal cells although decreased expression of ERß in the adult prostate may be related to dysplasia upon aging. An alteration in steroid receptors may directly influence the expression of key developmental genes in the prostate. We have recently found specific changes in the expression of the hox-13 paralogues as well as in Nkx3.1 in the estrogenized prostate. Future research is aimed at defining these alterations at the cellular and molecular level.

This work will serve as a model for what might be expected to occur in the prostate gland's of sons of DES-exposed mothers. Between 1950-1971, women received diethylstilbestrol during pregnancy to decrease incidence of miscarriage. It was found in 1971 that daughters of DES-exposed mothers had a higher incidence of vaginal carcinoma and its use was discontinued. Little is known about potential problems that may arise in DES-exposed sons but it is important to note that the prostate gland and vagina arise from the same structure embryologically (urogenital sinus). Sons exposed in utero to DES between 1950 and 1970 are just now entering the age of "natural" prostatic disease and it will be of clinical importance to determine whether their disease profile is different or more aggressive. This research will also be used as a model for toxicologic exposure to environmental and dietary estrogens which is a major problem now confronting the scientific and medical community.  

Clinical Interests

I am the Director of the University Andrology Laboratoy at the University of Illinois. This laboratory services the Department of Obstetrics & Gynecology fertility practice at the University, performing all male fertility diagnostic tests (semen analysis, antisperm antibodies, sperm penetration assays) as well as preparation of semen specimens for therapeutic artificial insemination. We perform extensive diagnostic and therapeutic services for the Department of Urology on the west campus of the University of Illinois at Chicago Medical Center.  Our University Andrology Laboratory is located in the Out-Patient Care Center (OCC) on the corner of Taylor and Wood Streets.

        Fertility Center
        Suite 4A
        1801 West Taylor Street
        Chicago, IL 60612   

In addition, we operate a large Client Depositor (Patient) Sperm Bank.  I am certified as a High Complexity Laboratory Director by the American Association of Bioanalysts and our laboratories are CLIA accredited and CAP/COLA certified. Our sperm bank is a member of the AATB and is licensed by the New York State Department of Health.

 


Bibliography

Research:

Huang L, Pu Y, Alam S, Birch L, Prins GS. Review: Estrogenic Regulation of Signaling Pathways and Homeobox Genes during Prostate Development. J Andrology. (submitted), 2003.

Woodham C, Birch L, Prins GS: Neonatal estrogens down regulate prostatic androgen receptor levels through a proteosome-mediated protein degradation pathway. Endocrinology 144(10):(in press), 2003.

Gilleran JP, Putz O, DeJong M, DeJong S, Birch L, Pu YB, Huang L, Prins GS: The role of prolactin in the prostatic inflammatory response to neonatal estrogen. Endocrinology 144:2046-2054, 2003.

Prins GS, Chang WY, Wang Y, van Breeman RB: Retinoic acid receptors and retinoids are up-regulated in the developing and adult rat ventral prostate by neonatal estrogen exposure. Endocrinology 143:3628-3640, 2002.

Prins GS, Birch L, Couse JF, Choi I, Katzenellenbogen B,  Korach KS:  Estrogen imprinting of the developing prostate gland is mediated through stromal ERa:  Studies with  aERKO and  ßERKO mice. Cancer Research  61:6089-6097, 2001.

Prins GS, Birch L, Habermann H, Chang WC, Tebeau C, Putz O, Bieberich C:  Influence of neonatal estrogens on rat prostate development.  Reprod Fertil Dev 13:1-2. 2001.

Wang Y, Chang WY, Prins GS, van Breeman RB:  Simultaneous determination of all-trans, 9-cis, 13-cis retinoic acid and retinol in rat prostate using liquid chromatography - mass spectrometry.  J Mass Spectroscopy 36:882-888, 2001.

Putz O, Kim S, Schwartz, R Cooper, G LeBlanc, Prins GS: Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: I. Effects on the prostate gland. Biology of Reproduction 65:1496-1505,2001.

Putz O, Schwartz, Kim S, G LeBlanc, R Cooper, Prins GS: Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: II. Effects on male puberty and the reproductive tract. Biology of Reproduction 65:1506-1517, 2001.

Habermann H, Chang W, Birch L, Mehta P, Prins GS:  Developmental exposure to estrogens alters epithelial cell adhesion and gap junction proteins in the adult rat prostate. Endocrinology 142:359-369, 2001.

Prins GS: Molecular biology of the androgen receptor. Mayo Clinic Proceedings: Testosterone Replacement in Elderly Men. 75:S32-35, 2000.

Jarred RA, Cancilla B, Prins GS, Cunha GR, Risbridger GP: Evidence that estrogens directly alter androgen regulated prostate development.  Endocrinology 141:3471-3477, 2000.

Chang WY, Birch L, Woodham C, Gold L, Prins GS: Neonatal estrogen exposure alters the TGFb signaling system in the developing rat prostate and interrupts TGFß-mediated differentiation of the epithelium. Endocrinology 140:2801-2813, 1999.

Chang WY, Prins GS: Estrogen receptor-beta: Implications for the prostate gland. Prostate 40:115-124, 1999.

Chang WY, Wilson MJ, Birch L, Prins GS: Neonatal estrogen stimulates proliferation of periductal fibroblasts and alters the extracellular matrix composition in the rat prostate.  Endocrinology 140:405-415, 1999.

Prins GS, Marmer M, Woodham C, Chang W, Kuiper G, Gustafsson J-A, Birch L: Estrogen receptor beta mRNA ontogeny in the prostate of normal and neonatally estrogenized rats. Endocrinology 139:874-883, 1998.

Prins GS and L Birch: Neonatal estrogen exposure up-regulates estrogen receptor alpha expression in the developing and adult rat prostate lobes. Endocrinology 138:1801-1809, 1997.

Prins GS: Developmental estrogenization of the prostate gland. In: Prostate: Basic and Clinical Aspects. Ed: Rajesh K. Naz, CRC Press Inc., Boca Raton, Florida, Chpt 10, pg 247-263, 1997.

Prins GS, Birch L: The developmental pattern of androgen receptor expression in the rat prostate lobes is altered following neonatal exposure to estrogen. Endocrinology 136:1303-1314, 1995.

Prins GS and C Woodham: Autologous regulation of androgen receptor mRNA in the separate lobes of the rat prostate gland. Biology of Reproduction 53:609-619, 1995.

Prins GS, Birch L:  Immunocytochemical analysis of androgen receptor along the ducts of the separate rat prostate lobes following androgen withdrawal and replacement.  Endocrinology 132:169-178 1993.

Prins GS, Woodham C, Lepinske M, Birch L:  Effects of neonatal estrogen on prostatic secretory genes and their correlation with androgen receptor expression in the adult rat prostate lobes.  Endocrinology 132:2387-2398, 1993.

Prins, GS: Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression. Endocrinology 130:2401-2412, 1992.

Prins GS, Cooke P, Birch L, Donjacour AA, Yalcinkaya T, Siiteri PK, Cunha, GR: Androgen receptor expression and 5-a-reductase activity along the proximal-distal axis of the rat prostatic duct.  Endocrinology 130:3066-3073, 1992.

Prins GS, Birch L, Greene GL: Androgen receptor localization in different cell types of the adult rat prostate.  Endocrinology 129:3187-3199, 1991.

Clinical:

Habermann H, Habermann W, Ray V, Prins GS: Gap Junctions in Prostate Disease. In: Andrology in the 21st Century. Ed: B. Robaire, Chemes H, Morales CR, Medimound Publications, pg 595-600, 2001

Habermann H, Ray V, Habermann W, Prins GS: Alterations in gap junction protein expression in human BPH and prostate cancer. J Urology 166, 2267-2273, 2001.

Cinar B, Koeneman KS, Edland M, Prins GS, Zhau HE, Chung LWK: Androgen receptor mediates the reduced tumor growth, enhanced androgen responsiveness and selected target gene transactivation in a human prostate cancer cell line. Cancer Research 61:7310-7317, 2001.

Small E, Taplin ME, Prins GS: The androgen receptor and the physiology and endocrinology of the prostate gland. In: Comprehensive Textbook of Genitourinary Oncology, Second edition. Ed: NJ Vogelzang, P Scardino, WU Shipley, DS Coffey, Williams & Wilkins, Baltimore, 2000.

Griffiths K, Denis LJ, Behre HE, Kreig M, Kyprianou N, Lee C, Mahler C, Petritisch P, Prezioso D, Prins GS, Tunn U, Vermeulen A: Oestrogens and Prostatic Disease: An IPHC Study Group. Prostate 45:87-100, 2000.

Prins GS: Molecular biology of the androgen receptor. Mayo Clinic Proceedings: Testosterone Replacement in Elderly Men. 75:S32-35, 2000.

Habermann, H, Seo R, Cieslak J, Niederberger C, Prins GS, Ross L: In vitro fertilization outcomes after intracytoplasmic sperm injection with fresh or frozen-thawed testicular spermatozoa. Fertility & Sterility 73:955-960, 2000.

Prins GS, Dolgina R, Studney P, Kaplan B, Ross L, Niederberger C: Quality of cryopreserved testicular sperm in patients with obstructive and non-obstructive azoospermia. J Urology 160 : 1504-1508, 1999.

Prins GS, Sklarew RJ, Pertschuk LP: Image analysis of androgen receptor immunostaining in prostate tumors accurately predicts response to hormonal therapy. J Urology 159:641-649, 1998.

Kasper S, Sheppard PC, Yan Y, Pettigrew N, Prins GS, Dodd JG, Duckworth ML, Matusik RJ: Development and progression of prostate tumors in transgenic mice by probasin targeted SV40 large T-antigen: A model for prostate cancer. Laboratory Investigation 78:319-333, 1998.

Yong EL, Tut TG, Ghadessy FJ, Prins GS, Ratnam SS: Partial androgen insensitivity and correlations with the predicted three dimensional structure of the androgen receptor ligand-binding domain. Molecular & Cellular Endocrinology 137:41-50, 1998.

Roman BL, Timms BG, Prins GS, Peterson RE: In utero and lactational exposure of the male rat to 2,3,7,8-Tetrachlorodibenzo-p-dioxin impairs prostate development: 2. Effects on growth and cytodifferentiation. Toxicology and Applied Pharmacology 150(2): 254270, 1998.

Prins GS: Semen. In: Encyclopedia of Reproduction. Ed: E. Knobil and JD Neill, Academic Press, pg 360-367, 1998.

Prins GS, Jung MH, Vellanoweth RL, Chatterjee B, Roy AK: Age-dependent expression of the androgen receptor gene in the prostate and its implication in cellular differentiation and hyperplasia. Developmental Genetics 18:99-106, 1996.

Small E and Prins GS: Physiology and endocrinology of the prostate. In: Comprehensive Textbook of Genitourinary Oncology. Ed: NJ Vogelzang, P Scardino, WU Shipley, DS Coffey, Williams & Wilkins, Baltimore, Chpt 37, pg 600-620, 1995.

Knudson G, Ross LS, Stuhldreher D, Houlihan D, Bruns E, Prins GS: Prevalence of sperm bound antibodies in infertile men with varicocele: The effect of varicocele ligation on antibody levels and semen response. J Urology 151:1260-1262, 1994.

Scommegna A, Ye S, Prins GS: Bromocryptine reverses the inhibitory effect of macrophages on sperm motility. Fertility & Sterility 61:331-335, 1994.

Sawetawan C, Bruns E, Prins GS: Improvement of post-thaw motility in poor quality human semen. Fertility & Sterility 60:706-710, 1993.

Kramer RY, Garner DL, Bruns ES, Ericsson SA, Prins GS: Comparison of motility and flow cytometric assessments of seminal quality in fresh, 24-hour extended and cryopreserved human spermatozoa. J Andrology 14:374-384, 1993.


 

Gail S. Prins, Ph.D.

University of Illinois at Chicago

Department of Urology; M/C 955

820 S. Wood Street

Chicago, IL  60612-7310

(312) 413 - 9766   Voice Number

(312) 996 - 1291   Fax Number

gprins@uic.edu    email address

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