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Temporal relationships among testosterone production, steroidogenic acute regulatory protein (StAR), and P450 side-chain cleavage enzyme (P450scc) during Leydig cell aging.
J Androl. 2005 Jan-Feb; 26(1):25-31.JA

Abstract

Previous studies have shown that the capacity of Leydig cells from aged (21-24-month-old) Brown Norway rats to produce testosterone is reduced from young (4-month-old) levels, and that this is correlated with reductions in steroidogenic acute regulatory protein (StAR), peripheral benzodiazapine receptor (PBR), and the levels and activities of the steroidogenic enzymes. The age(s) at which particular changes in the steroidogenic pathway occur, and the relationship of particular changes to reduced testosterone production, are not known. We examined 3 critical components of the steroidogenic pathway, cyclic adenosine monophosphate (cAMP) production, StAR, and P450 side-chain cleavage enzyme (P450scc) in relationship to age-related decreases in testosterone production. Leydig cells isolated from Brown Norway rats of increasing ages (4, 9, 15, and 20 months) were evaluated. The ability of Leydig cells to produce testosterone was reduced at 9 months, although not significantly. Significant reductions in testosterone production were first seen in cells isolated from rats of 15 months of age, and further reductions occurred thereafter. Reduced testosterone was correlated with reductions in StAR, P450scc mRNA, and protein. Significant decline in luteinizing hormone-stimulated intracellular cAMP levels was seen by 9 months, before significant reductions in testosterone, StAR, and P450scc. Further declines in cAMP levels were seen at 15 and 20 months. These studies suggest that age-related reductions in intracellular cAMP may lead to the reduced testosterone production that characterizes aged Leydig cells. This suggestion is supported by recent studies from our lab demonstrating that long-term (3 days) culture of old Leydig cells with dbcAMP restored testosterone production to levels approximating those of young cells.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. lluo@hsph.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15611563

Citation

Luo, Lindi, et al. "Temporal Relationships Among Testosterone Production, Steroidogenic Acute Regulatory Protein (StAR), and P450 Side-chain Cleavage Enzyme (P450scc) During Leydig Cell Aging." Journal of Andrology, vol. 26, no. 1, 2005, pp. 25-31.
Luo L, Chen H, Zirkin BR. Temporal relationships among testosterone production, steroidogenic acute regulatory protein (StAR), and P450 side-chain cleavage enzyme (P450scc) during Leydig cell aging. J Androl. 2005;26(1):25-31.
Luo, L., Chen, H., & Zirkin, B. R. (2005). Temporal relationships among testosterone production, steroidogenic acute regulatory protein (StAR), and P450 side-chain cleavage enzyme (P450scc) during Leydig cell aging. Journal of Andrology, 26(1), 25-31.
Luo L, Chen H, Zirkin BR. Temporal Relationships Among Testosterone Production, Steroidogenic Acute Regulatory Protein (StAR), and P450 Side-chain Cleavage Enzyme (P450scc) During Leydig Cell Aging. J Androl. 2005 Jan-Feb;26(1):25-31. PubMed PMID: 15611563.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Temporal relationships among testosterone production, steroidogenic acute regulatory protein (StAR), and P450 side-chain cleavage enzyme (P450scc) during Leydig cell aging. AU - Luo,Lindi, AU - Chen,Haolin, AU - Zirkin,Barry R, PY - 2004/12/22/pubmed PY - 2005/4/14/medline PY - 2004/12/22/entrez SP - 25 EP - 31 JF - Journal of andrology JO - J Androl VL - 26 IS - 1 N2 - Previous studies have shown that the capacity of Leydig cells from aged (21-24-month-old) Brown Norway rats to produce testosterone is reduced from young (4-month-old) levels, and that this is correlated with reductions in steroidogenic acute regulatory protein (StAR), peripheral benzodiazapine receptor (PBR), and the levels and activities of the steroidogenic enzymes. The age(s) at which particular changes in the steroidogenic pathway occur, and the relationship of particular changes to reduced testosterone production, are not known. We examined 3 critical components of the steroidogenic pathway, cyclic adenosine monophosphate (cAMP) production, StAR, and P450 side-chain cleavage enzyme (P450scc) in relationship to age-related decreases in testosterone production. Leydig cells isolated from Brown Norway rats of increasing ages (4, 9, 15, and 20 months) were evaluated. The ability of Leydig cells to produce testosterone was reduced at 9 months, although not significantly. Significant reductions in testosterone production were first seen in cells isolated from rats of 15 months of age, and further reductions occurred thereafter. Reduced testosterone was correlated with reductions in StAR, P450scc mRNA, and protein. Significant decline in luteinizing hormone-stimulated intracellular cAMP levels was seen by 9 months, before significant reductions in testosterone, StAR, and P450scc. Further declines in cAMP levels were seen at 15 and 20 months. These studies suggest that age-related reductions in intracellular cAMP may lead to the reduced testosterone production that characterizes aged Leydig cells. This suggestion is supported by recent studies from our lab demonstrating that long-term (3 days) culture of old Leydig cells with dbcAMP restored testosterone production to levels approximating those of young cells. SN - 0196-3635 UR - https://www.unboundmedicine.com/medline/citation/15611563/Temporal_relationships_among_testosterone_production_steroidogenic_acute_regulatory_protein__StAR__and_P450_side_chain_cleavage_enzyme__P450scc__during_Leydig_cell_aging_ DB - PRIME DP - Unbound Medicine ER -