Dibutyryl cyclic adenosine monophosphate restores the ability of aged Leydig cells to produce testosterone at the high levels characteristic of young cells.
The wealth of knowledge about the function and regulation of adult Leydig cells, the cells within the mammalian testis that produce testosterone, make these cells ideal for studying principles and mechanisms of aging. A hallmark of mammalian aging is decreased serum testosterone concentration. In the Brown Norway rat, this has been shown to be associated with the reduced ability of aged Leydig cells to produce testosterone in response to LH. Herein, we demonstrate that culturing the aged cells with dibutyryl cAMP, a membrane-permeable cAMP agonist that bypasses the LH receptor-adenlyly cyclase cascade, restores testosterone production to levels comparable to those of young cells and also restores steroidogenic acute regulatory protein and P450scc, the proteins involved in the rate-limiting steps of steroidogenesis. These results strongly suggest that signal transduction deficits are responsible for reduced steroidogenesis by aged Leydig cells and that bypassing signal transduction reverses the steroidogenic decline by the aged cells.
Chen
Haolin
H
Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. hchen@jhsph.edu.
Liu
June
J
Luo
Lindi
L
Zirkin
Barry R
BR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011974:Receptors, LH / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D011974:Receptors, LH; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D003994:Bucladesine; D002786:Cholesterol Side-Chain Cleavage Enzyme; D000262:Adenylyl Cyclases