Regulation of Leydig cell steroidogenic function during aging.
This article summarizes a talk on Leydig cell aging presented at the 1999 Annual Meeting of the Society for the Study of Reproduction. In the Brown Norway rat, serum testosterone levels decrease with aging, accompanied by increases in serum FSH. The capacity of Leydig cells to produce testosterone is higher in young than in old rats. Binding studies with hCG revealed reduced receptor number in old vs. young Leydig cells. In response to incubation with LH, cAMP production was found to be reduced in old vs. young Leydig cells, indicating that signal transduction mechanisms in the old cells are affected by aging. Steroidogenic acute regulatory protein and mRNA levels are reduced in old Leydig cells, suggesting that there may be deficits in the transport of cholesterol to the inner mitochondrial membrane of aged cells. The activity of P450 side-chain cleavage enzyme is reduced in old vs. young cells, as are the activities of each of 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/C17-20 lyase, and 17-ketosteroid reductase. Serum LH levels do not differ between young and old rats, and the administration of LH failed to induce old Leydig cells to produce high (young) testosterone levels, suggesting that the cause of age-related reductions in steroidogenesis is not LH deficits. We hypothesized that reactive oxygen, produced as a by-product of steroidogenesis itself, might be responsible for age-related reductions in testosterone production by the Leydig cells. Consistent with this, long-term suppression of steroidogenesis was found to prevent or delay the reduced steroidogenesis that accompanies Leydig cell aging. A possible explanation of this finding is that long-term suppression of steroidogenesis prevents free radical damage to the cells by suppressing the production of the reactive oxygen species that are a by-product of steroidogenesis itself.
Zirkin
B R
BR
Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA. brzirkin@jhsph.edu
Chen
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H
D000375:Aging / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D016922:Cellular Senescence / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D018871:Endoplasmic Reticulum, Smooth / Q000201:enzymology*; D006801:Humans; D007985:Leydig Cells / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*
D017382:Reactive Oxygen Species; D011974:Receptors, LH; D013256:Steroids; D007986:Luteinizing Hormone; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme