Mullerian-inhibiting substance inhibits rat Leydig cell regeneration after ethylene dimethanesulphonate ablation

UMMS Affiliation

Department of Pediatrics; Department of Cell Biology; Lee Lab

Publication Date


Document Type



3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Animals; Anti-Mullerian Hormone; Cell Count; Cell Division; Cholesterol Side-Chain Cleavage Enzyme; Glycoproteins; In Situ Nick-End Labeling; Leydig Cells; Luteinizing Hormone; Male; Mesylates; Organ Size; Rats; Rats, Sprague-Dawley; Steroid 17-alpha-Hydroxylase; Testicular Hormones; Testis; Testosterone


Cell and Developmental Biology | Endocrinology, Diabetes, and Metabolism | Pediatrics


The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered by intratesticular injection for 4 days (Days 11-14 after EDS). On Days 15 and 35 after EDS (1 and 21 days post-MIS injections), endocrine function was assessed and testes were collected for stereology, immunohistochemistry, and assessment of proliferation and steroidogenesis. Although serum testosterone and luteinizing hormone (LH) were no different, intratesticular testosterone was higher on Day 35 in MIS-treated animals. At both time points, intratesticular 5alpha-androstan-3alpha,17beta-diol concentrations were much higher than that of testosterone. MIS-treated animals had fewer mesenchymal precursors on Day 15 and fewer differentiated Leydig cells on Day 35 with decreased numbers of BrdU+ nuclei. Apoptotic interstitial cells were observed only in the MIS-treated testes, not in the vehicle-treated group on Day 15. These data suggest that MIS inhibits regeneration of Leydig cells in EDS-treated rats by enhancing apoptotic cell death as well as by decreasing proliferative capacity.

DOI of Published Version



Biol Reprod. 2004 Mar;70(3):600-7. Epub 2003 Oct 29. Link to article on publisher's site

Journal/Book/Conference Title

Biology of reproduction


At the time of publication, Mary Lee and Xiufeng Wu were not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID