This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zirkin, B. R. Search for Related Content PubMed Articles by Zirkin, B. R.

Response to Commentaries

Culty M, Luo L, Yao Z, Chen H, Papadopoulos V, Zirkin B. Cholesterol transport, peripheral benzodiazepine receptor, and steroidogenesis in aging Leydig cells. J Androl. 2002 ;23:439–447.[Abstract/Free Full Text]

We now know a great deal about age-related Leydig cell deficits. Aging Leydig cells are characterized by reductions in luteinizing hormone receptor number, cyclic adenosine monophosphate (cAMP) production, steroidogenic acute regulatory (StAR) protein, peripheral benzodiazepine receptor (PBR), cholesterol transport, and conversion of cholesterol to testosterone by enzymes residing in the mitochondria and smooth endoplasmic reticulum. Is there any one among these changes that leads to the rest? Recently obtained results strongly suggest that the reduced ability of Leydig cells to produce cAMP is likely to represent a critical, initiating event that leads to downstream deficits in the steroidogenic machinery; and, consistent with this, that it may be possible to restore steroidogenic function to the old Leydig cells by bypassing cAMP. Just how deficits in signal transduction affect cholesterol transport, and the exact relationship of the latter to PBR and StAR, remain to be determined.

Although the causes of age-related Leydig cell deficits remain elusive, support is emerging for the idea that reactive oxygen is likely to play a major role in the reduced ability of old Leydig cells to produce testosterone. The risk of damage from reactive oxygen species is particularly high for steroidogenic cells because reactive oxygen is produced both via the electron transport chain and the P450 enzymes. Recent studies from our laboratory indicate that the production of superoxide increases with Leydig cell aging (Chen et al, 2001), and that the expression of genes for SOD1, catalase, and glutathione peroxidase, the products of which protect Leydig cells from oxidative stress, are reduced in aging Leydig cells. We speculate that aging may alter the ability of the Leydig cell to respond to stress, and that this leads to damage to the cell's steroidogenic machinery and ultimately to reduced steroidogenesis. The "maddening puzzle" appears to be on the edge of becoming less maddening.

References

Chen H, Cangello D, Benson S, Folmer J, Zhu H, Trush MA, Zirkin BR. Age-related increase in mitochondrial superoxide generation in the testosterone of Brown Norway rat testes: relationship to reduced steroidogenic function? Exp Gerontol. 2001; 36: 1361 -1373.[Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zirkin, B. R. Search for Related Content PubMed Articles by Zirkin, B. R.