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Abstract

Deletion of the Igf1 gene: Suppressive effects on adult Leydig cell development 
Hu,Guo-Xin; Lin,Han; Chen,Guo-Rong; Chen,Bing-Bing; Lian,Qing-Quan; Hardy,Dianne O.; Zirkin,Barry R.; Ge,Renshan
Journal of Andrology 31(4): 379-387
Publication date: 2010


Deletion of the insulin-like growth factor 1 (Igf1) gene wasshown in previous studies to result in reduced numbers of Leydigcells in the testes of 35 day-old mice, and in reduced circulatingtestosterone levels. In the current study, we asked whetherdeletion of the Igf1 gene affects the number, proliferation,and/or steroidogenic function of some or all of the precursorcell types in the developmental sequence that leads to the establishmentof adult Leydig cells (ALCs). Decreased numbers of cells inthe Leydig cell lineage (i.e. 3betaHSD-positive cells) wereseen in testes of postnatal day (PND) 14-90 Igf1 mice comparedto age-matched Igf1 controls. The development of ALCs proceedsfrom stem (SLCs) through progenitor (PLCs) and immature (ILCs)Leydig cells. The BrdU labeling index of putative SLCs was similarin the Igf1 and Igf1 mice. In contrast, the labeling indexof PLCs was reduced in the Igf1 mice at each of PND 14 through35, and that of more mature Leydig cells (referred to hereinas LCs, a combination of ILCs plus ALCs) was reduced from PND21 through 56. In Igf1 mice that received recombinant IGF-I,the labeling indices of PLCs and LCs were similar to those ofaged-matched Igf1 mice, indicating that the reductions inthe labeling indices seen in the PLCs and LCs of the Igf1mice were a consequence of reduced IGF-I. At each of PND 21through 90, testicular testosterone concentrations were significantlyreduced in the Igf1 mice, as were the expressions of testis-specificmRNAs involved in steroidogenesis, including StAR, Cyp11a1,and Cyp17a. The increased expression of the gene for 5alpha-reductase(Srd5a1) in adult Igf1 testes suggests that the depletionof Igf1 might suppress or delay Leydig cell maturation. Theseobservations, taken together, indicate that the reduced numbersof Leydig cells in the adult testes of Igf1 mice result atleast in part from altered proliferation and differentiationof ALC precursor cells, but not of the stem cells that giverise to these cells.