Effect of retinoid status on the messenger ribonucleic acid expression of nuclear retinoid receptors alpha, beta, and gamma, and retinoid X receptors alpha, beta, and gamma in the mouse testis.
The testicular gene expression of the retinoic acid receptors, RAR alpha, -beta, and -gamma, was studied in normal mice and in vitamin A-deficient mice after the administration of all-trans-retinoic acid (ATRA). All three types of RARs were expressed in normal and/or vitamin A-deficient testes. Only the expression of RAR beta messenger RNA was transiently induced within 24 h after ATRA injection. ATRA-induced RAR beta expression was also found in purified Sertoli cells, suggesting that these cells mediate at least part of the effect of retinoids on germ cells. When an equimolar amount of retinol was administered instead of ATRA, no induction of RAR beta was seen at the point of maximal induction by ATRA, suggesting that the effect of retinol was delayed and probably less. The related nuclear receptors, RXR alpha, -beta, and, for the first time, gamma, were also shown to be present in the mouse testis. Upon administration of ATRA, messenger RNA expression of RXR alpha and -beta did not change significantly. The expression of RXR gamma was too low to allow quantification. Finally, the effect of the retinoid metabolism inhibitor liarozole on ATRA-induced proliferation of A spermatogonia was examined. The labeling index of A spermatogonia, 24 h after the administration of 0.25 mg ATRA, was significantly lowered by liarozole due to a shift of the maximal 5-bromo-deoxyuridine incorporation to an earlier point (20 h). This indicates that liarozole delays retinoid metabolism, thereby increasing the actual ATRA concentration, and more importantly, that ATRA by itself is an active retinoid in spermatogenesis. Apparently, ATRA does not need to be metabolized to 4-oxo-RA, which was previously shown to be a more potent inducer of spermatogonial proliferation than ATRA, to be effective.
Gaemers
I C
IC
Department of Cell Biology, Utrecht University Medical School, The Netherlands.
van Pelt
A M
AM
van der Saag
P T
PT
Hoogerbrugge
J W
JW
Themmen
A P
AP
de Rooij
D G
DG
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000097768:Retinoic Acid Receptor gamma
D007093:Imidazoles; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta; C002202:4-oxoretinoic acid; C061121:liarozole