Age-related decreases in Leydig cell testosterone production are not restored by exposure to LH in vitro.
Aging in Brown Norway rats is associated with reduced Leydig cell T production. To address the mechanism by which aging Leydig cells become steroidogenically hypofunctional, Leydig cells from young and old rat testes were isolated and cultured long-term with LH. Leydig cells isolated from young rats that had received LH-suppressive T implants served as positive controls. The ability of young control Leydig cells to produce T at high levels was sustained over a 3-d culture period. T production by cells from young LH-suppressed rats increased over this period, almost to control levels. In contrast, culture of the steroidogenically hypofunctional old Leydig cells with LH failed to increase their T production, suggesting that LH stimulation, by itself, is unable to reverse the steroidogenic deficits of old Leydig cells. Reduced numbers of LH binding sites characterized Leydig cells from old rats and LH-suppressed young rats. However, whereas Leydig cells from young LH-suppressed rats produced cAMP at the high levels of young control cells, the old cells produced far less cAMP, suggesting that old Leydig cells have defects in the LH-cAMP signaling cascade. When stimulated with forskolin, old cells produced the same amount of cAMP as young control and young LH-suppressed cells, suggesting that adenylate cyclase is maintained in the old cells. Taken together, these results suggest that inefficient signal transduction may explain the reduced steroidogenesis that characterizes old Leydig cells.
Chen
Haolin
H
Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. hchen@jhsph.edu
Hardy
Matthew P
MP
Zirkin
Barry R
BR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011974:Receptors, LH / Q000187:drug effects; D013739:Testosterone / Q000096:biosynthesis*
D011974:Receptors, LH; D013739:Testosterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP