Steroidogenic fate of the Leydig cells that repopulate the testes of young and aged Brown Norway rats after elimination of the preexisting Leydig cells.
The capacity of Brown Norway rat Leydig cells to produce testosterone (T) decreases with aging. In a previous study, we reported that a new generation of Leydig cells can be restored in both young and old rat testes after a single injection of ethane dimethanesulfonate (EDS), and that the abilities of the new Leydig cells in young and old rats to produce T were equivalent. Our objective herein was to compare the steroidogenic fate of the new Leydig cells over time. Young (3 month-old) and old (18 month-old) rats were injected with EDS to eliminate the existing Leydig cells. Ten weeks after EDS, Leydig cells had been restored and T production by the new Leydig cells isolated from young and old rat testes was equivalent. Thirty weeks after EDS treatment of young rats, the ability of the new Leydig cells to produce T had not diminished from 10 weeks post-EDS. In contrast, at 30 weeks post-EDS, T production by new cells in old rat testes was reduced significantly from the 10-week level. Serum T levels at 10 and 30 weeks were consistent with Leydig cell T production. Serum LH levels did not differ in any group. Thus, although the Leydig cells restored to both young and old rats after EDS initially produced T at high, equivalent levels, the cells in the old testes did not maintain this ability. These results suggest that: 1) the cells from which new populations of Leydig cells are derived may differ depending upon the age of the rat; and/or 2) factors extrinsic to the new Leydig cells in young and old testes differ, and it is these differences that are responsible for reductions in T by the newly formed Leydig cells in the testes of old rats.
The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: hchen13@jhu.edu.
Haolin
H
Chen
The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jingjing
J
Guo
The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Renshan
R
Ge
The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Qingquan
Q
Lian
The Research Institute of the McGill University Health Centre, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Department of Biochemistry, McGill University, Montreal, Canada; Department of Pharmacology & Therapeutics, McGill University, Montreal, Canada.
Vassilios
V
Papadopoulos
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Barry R
BR
Zirkin
D000375:Aging / Q000502:physiology*; D000818:Animals; D007985:Leydig Cells / Q000378:metabolism* / Q000473:pathology*; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008698:Mesylates / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN; D013739:Testosterone / Q000097:blood*
D008698:Mesylates; D013739:Testosterone; D007986:Luteinizing Hormone; C002994:ethylene dimethanesulfonate
Aging; EDS; Leydig cells; Steroidogenesis