PMID- 9751509
OWN - NLM
STAT- MEDLINE
DCOM- 19981008
LR  - 20181201
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 139
IP  - 10
DP  - 1998 Oct
TI  - The effect of 9-cis-retinoic acid on proliferation and differentiation of a 
      spermatogonia and retinoid receptor gene expression in the vitamin A-deficient 
      mouse testis.
PG  - 4269-76
AB  - Retinoid X receptors (RXRs) are key regulators in retinoid signaling. Knowledge 
      about the effects of 9-cis-retinoic acid (9-cis-RA), the natural ligand for the 
      RXRs, may also provide insight in the functions of RXRs. In this study, the 
      effect of 9-cis-RA on spermatogenesis in vitamin A-deficient (VAD) mice was 
      examined. Administration of 9-cis-RA stimulated the differentiation and 
      subsequent proliferation of the growth-arrested A spermatogonia in the testis of 
      VAD mice. However, compared with all-trans-retinoic acid (ATRA), relatively 
      higher doses of 9-cis-RA were necessary. This could not simply be due to a lower 
      or delayed activity of 9-cis-RA, as simultaneous administration of ATRA and 
      9-cis-RA did not cause a synergistic effect. Instead, the presence of 9-cis-RA 
      diminished the effect of ATRA by approximately one third. Studies of in vivo 
      transport and metabolism showed that ATRA and 9-cis-RA, after administration to 
      VAD mice, penetrated the testis equally well. However, 9-cis-RA was metabolized 
      much faster than ATRA, and other metabolites were formed. This may account for 
      the above-described differential effects of ATRA and 9-cis-RA on spermatogenesis. 
      Similar to ATRA, 9-cis-RA transiently induced the messenger RNA expression of the 
      nuclear RA receptor RAR beta, suggesting a role for this receptor in the effects 
      of retinoids on the differentiation and proliferation of A spermatogonia. In 
      contrast, the messenger RNA expression of the nuclear retinoid receptors RXR 
      alpha, -beta, and -gamma was not changed significantly by administration of their 
      ligand, 9-cis-RA. Hence, 9-cis-RA does not seem to exert its effect on 
      spermatogenesis through altered expression of the RXRs.
FAU - Gaemers, I C
AU  - Gaemers IC
AD  - Department of Cell Biology, Medical School, Utrecht University, The Netherlands. 
      gaemers@nki.nl
FAU - Sonneveld, E
AU  - Sonneveld E
FAU - van Pelt, A M
AU  - van Pelt AM
FAU - Schrans, B H
AU  - Schrans BH
FAU - Themmen, A P
AU  - Themmen AP
FAU - van der Saag, P T
AU  - van der Saag PT
FAU - de Rooij, D G
AU  - de Rooij DG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (retinoic acid receptor beta)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Male
MH  - Mice
MH  - RNA, Messenger/analysis
MH  - Receptors, Retinoic Acid/*drug effects/genetics
MH  - Retinoid X Receptors
MH  - Spermatogenesis/drug effects
MH  - Spermatogonia/*drug effects
MH  - Testis/*drug effects/metabolism
MH  - Transcription Factors/*drug effects/genetics
MH  - Tretinoin/*pharmacology
MH  - Vitamin A Deficiency/*physiopathology
EDAT- 1998/09/29 00:00
MHDA- 1998/09/29 00:01
CRDT- 1998/09/29 00:00
PHST- 1998/09/29 00:00 [pubmed]
PHST- 1998/09/29 00:01 [medline]
PHST- 1998/09/29 00:00 [entrez]
AID - 10.1210/endo.139.10.6272 [doi]
PST - ppublish
SO  - Endocrinology. 1998 Oct;139(10):4269-76. doi: 10.1210/endo.139.10.6272.