Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor
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Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor. / De Gendt, Karel; Atanassova, Nina; Tan, Karen A L; de França, Luiz Renato; Parreira, Gleydes Gambogi; McKinnell, Chris; Sharpe, Richard M; Saunders, Philippa T K; Mason, J Ian; Hartung, Stefan; Ivell, Richard; Denolet, Evi; Verhoeven, Guido.
In: ENDOCRINOLOGY, Vol. 146, No. 9, 01.09.2005, p. 4117-26.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor
AU - De Gendt, Karel
AU - Atanassova, Nina
AU - Tan, Karen A L
AU - de França, Luiz Renato
AU - Parreira, Gleydes Gambogi
AU - McKinnell, Chris
AU - Sharpe, Richard M
AU - Saunders, Philippa T K
AU - Mason, J Ian
AU - Hartung, Stefan
AU - Ivell, Richard
AU - Denolet, Evi
AU - Verhoeven, Guido
PY - 2005/9/1
Y1 - 2005/9/1
N2 - It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.
AB - It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.
KW - Age Factors
KW - Androgens
KW - Animals
KW - Cell Count
KW - Female
KW - Leydig Cells
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Microscopy, Electron
KW - Receptors, Androgen
KW - Sertoli Cells
KW - Testis
U2 - 10.1210/en.2005-0300
DO - 10.1210/en.2005-0300
M3 - SCORING: Journal article
C2 - 15919750
VL - 146
SP - 4117
EP - 4126
JO - ENDOCRINOLOGY
JF - ENDOCRINOLOGY
SN - 0013-7227
IS - 9
ER -