Successful islet/abdominal testis transplantation does not require Leydig cells.
Pancreatic islet allo- and xenografts are not rejected and exhibit long-term beta-cell function if transplanted into the abdominal testis of the diabetic host. Successful transplantation appears dependent on local factors unique to the abdominal testis. Because Leydig cells remain viable in abdominal testes, which also retain high levels of testosterone, the following question was addressed: do Leydig cells and/or their secretory products influence islet transplantability in the successful islet/abdominal testis transplantation model? Streptozotocin-induced diabetic rats (Sprague-Dawley) were injected with 75 mg/kg ethane dimethanesulfonate (EDS) to selectively eliminate Leydig cells prior to or following transplantation with islets isolated from the BBWORdr rat. Subcutaneous silastic tubes packed with estradiol prevented Leydig cell repopulation in the EDS-treated recipient. Grafted diabetic animals, including the EDS-treated rats with serum testosterone at castration levels, became nornoglycemic following islet transplantation and remained so far for up to ten months. Leydig cells were not observed in testes of the EDS- or EDS/estradiol-treated rats, whereas the transplanted islets within these testes appeared structurally normal and highly vascularized. Islets resided within the testicular interstitial compartment and contained alpha-, beta and delta-cells, as identified by electron microscopy. Beta cells were most prominent, contained secretory granules and exhibited a close structural and functional relationship with adjacent intraislet capillaries. We conclude that Leydig cells and Leydig cell secretory products, including testosterone, are not necessary for protecting islets against rejection and they do not play an obligatory role in the success of the islet/abdominal testis transplantation protocol. Leydig cells and Leydig cell secretory products do not promote long-term beta-cell function and are not required for the return to and maintenance of normoglycemia in the grafted diabetic rat.
Cameron
D F
DF
Department of Anatomy, University of South Florida, Tampa.
Whittington
K
K
Schultz
R E
RE
Selawry
H P
HP
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016381:Islets of Langerhans Transplantation; D007985:Leydig Cells / Q000502:physiology*; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000166:cytology / Q000276:immunology; D013739:Testosterone / Q000097:blood; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D001786:Blood Glucose; D008698:Mesylates; D013739:Testosterone; C002994:ethylene dimethanesulfonate