Mary Lee, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Cell Biology
   Pediatrics

Testicular Development

We are interested in understanding the role of Mullerian inhibiting substance in the testis and elucidating the hormonal and cellular interactions that are critical for testicular development.  Our research involves both clinical investigations and laboratory studies.  Our basic research efforts have focused on clarifying the paracrine and endocrine regulation of Leydig cell differentiation and on identifying the effects of persistent organic pollutants (endocrine disruptors, such as dioxins) on the developing male reproductive system.

Areas of research interest:

• Biology and regulation of Mullerian inhibiting substance
• Sexual differentiation and intersex disorders
• Testicular differentiation and development (fetal and postnatal) of Leydig cells
• The effects of environmental toxins on reproductive development
• Gonadal toxicity of chemotherapy and radiation for childhood malignancies

Figure 1. Mullerian Inhibiting Substance (MIS) is a negative regulator of progenitor Leydig cell proliferation and differentation and an inhibitor of adult Leydig cell androgen biosynthesis.  

Figure 2. TUNEL staining of representative light micrographs of 4-µm-thick testicular sections from MIS and control-treated rats on Day 15 after EDS treatment. A) Control rat. B and C) MIS-treated rats. Most of the TUNEL-positive nuclei are located within the seminferous tubules and correspond to germ cells. Arrow: interstitial cell with TUNEL-positive nucleus. Scale bar = (A and B) 100 µm and (C) 25 µm. (Salva A, et al. Biology of Reproduction 2004;70:600-607)

Representative Publications

Lee MM and Moshang T.  “Endocrine Disorders of the Newborn” In Avery GB, Fletcher MA and MacDonald  MG, eds.  Neonatology:  Pathophysiology and Management of the Newborn, 6^th Edition.  Philadelphia :  Lippincott Williams & Wilkins, 2005, pp pending.

Catlin EA and Lee MM.  “Neonatal endocrinology,” in DeAngelis CD, Feigin RD, McMillan JA, and Warshaw JB, eds.  Oski’s Pediatrics:  Principles and Practice, 4th ed., Philadelphia :  Lippincott, Williams & Wilkins, 2005, pp pending.

Hauser R, Williams P, Altshul L, Korrick S, Peeples L, Patterson D, Turner WE, Lee MM,  Revich B, Zeilert V, and Sergeyev O. Characterization and predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia.  Organohalogen Compounds, 2004; 66:3245-3251.

Wu XF, Arumugam R, Baker SP, and Lee MM.  Pubertal and adult Leydig cell function in Mullerian Inhibiting Substance (MIS/AMH) deficient mice.  Endocrinology, 2005; 146:589-595 (first published on-line October 28, 2004 ).

Lee MM.  “Molecular Genetic Control of Sex Differentiation,” in Eugster EA and Pescovitz OH, eds.  Pediatric Endocrinology: Mechanisms, Manifestations and Management.  Philadelphia :  Lippincott, Williams and Wilkins, 2004, 231-242.

Hardy O, Worley G, Lee MM, Chaing S, Mackey J, Crissman B, and Kishnani PS.  Hypothyroidism in Down Syndrome: Screening guidelines and testing methodology.  Am J Med Genet, 2004, 124A:436-437.

Misra M, MacLaughlin DT, Donahoe PK and Lee MM.  The role of Mullerian inhibiting substance in the evaluation of phenotypic females with mild degrees of virilization.  J Clin Endocrinol Metab, 2003, 88:787-797.

Lee MM, Sergeyev O, Williams P, Korrick S, Zeilert V, Revich B, and Hauser R. Physical growth and sexual maturation of boys in Chapaevsk, Russia.  J Pediatric Endocrinol, 2003, 16: 169-178.

Lee MM, Misra M, Donahoe PK and MacLaughlin DT.  MIS/AMH in the assessment of cryptorchidism and intersex conditions.   Mol Cell Endocrinol, 2003, 211:91-98.

Salva A, Hardy MP, Wu XF, Sottas CM, MacLaughlin DT, Donahoe PK, and Lee MM.  Mullerian Inhibiting Substance prevents rat Leydig cell degeneration after ethylene dimethanesulphonate (EDS) ablation.  Biol Reprod, 2004, 70:600-607 (first published on-line October 29, 2003 ).

Litton J, Rice A, Friedman N, Oden J, Lee MM and Freemark M.  Insulin pump therapy in infants and preschool children with type 1 diabetes mellitus.  J Ped, 2002, 141:490-495.

Sriraman V, Niu E, Matias JR, Donahoe PK, MacLaughlin DT, Hardy MP and Lee MM.  Mullerian Inhibiting Substance inhibits testosterone synthesis in adult rats.  J Androl, 2001, 22:750-758

Lane AH, Lee MM, Fuller AF, Kehas D, Donahoe PK, MacLaughlin DT.  Diagnostic utility of Mullerian inhibiting substance determination in patients with primary and recurrent granulosa cell tumors.  Gynecol Oncol 1999; 73:51-55.

Lee MM, Seah CC, Masiakos P, Sottas C, Preffer F, Donahoe PK, MacLaughlin DTM, and Hardy MP.  Mullerian inhibiting substance type II receptor expression and function in primary rat Leydig cells. Endocrinology, 1999; 140:2819-2827

Lee MM, Donahoe PK,   Silverman B, Hasegawa T, Hasegawa Y, Gustafson ML, Chang YC, and MacLaughlin DT.  Measurements of serum Mullerian Inhibiting Substance in the evaluation of children with nonpalpable gonads.  New Engl J Med, 1997; 336: 1480-1486.  

Potential Rotations for Students

1. Characterize the Leydig cell phenotype of different KO and transgenic models of specific genes relevant to reproductive development to determine the role of these genes in Leydig cell development: i.e. GPR54, androgen receptor, etc.
2. Examine the mechanisms underlying the inhibitory effects of dioxin on Leydig cell steroidogenesis and investigate the developmental basis of this.
3. Investigate the role of MIS in the development of Leydig cell tumors.
4. Examine MIS signaling in Leydig cells.

Biography

M.D., SUNY-Buffalo School of Medicine      1983
Resident in Pediatrics, Children's Hospital of Buffalo     1983-1986
Fellow, Pediatric Endocrinology and Metabolism, Children's Hospital of Philadelphia     1986-1989                         
Research fellow, Massachusetts General Hospital     1989-1992
Assistant Professor of Pediatrics, Harvard Medical School, Boston, MA     1993-2000
Associate Professor of Pediatrics, Duke University Medical Center, Durham, NC     2000-2004         

Prof of Pediatrics and Cell Biology  
Director, Ped Endo and Diabetes, UMass Medical School     Current               

Phone: 508-856-4280
E-mail: Mary.Lee@umassmemorial.org
Keywords: Reproductive Endocrinology, Transgenic Mice, Cell Biology, Male Reproductive Biology, Testis Development

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