Document Detail

Estrogen-regulated genes in rat testes and their relationship to recovery of spermatogenesis after irradiation.
MedLine Citation:
PMID:  21653891     Owner:  NLM     Status:  MEDLINE    
Despite numerous observations of the effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. Using rats in which irradiation had completely blocked spermatogonial differentiation, we previously showed that testosterone suppression with gonadotropin-releasing hormone-antagonist acyline and the antiandrogen flutamide stimulated spermatogenic recovery and that addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and using concurrent data on regulation of the genes by these hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or testosterone changes. Expression of 20 genes, largely in somatic cells, was up- or downregulated between 2- and 5-fold by E2. The unexpected and striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes suggested that these might represent noncoding mRNAs; indeed, we have identified several as miRNAs and their potential target genes in this system. We propose that genes for which expression levels are altered in one direction by irradiation and in the opposite direction by both testosterone suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.
Wei Zhou; Olga U Bolden-Tiller; Shan H Shao; Connie C Weng; Gunapala Shetty; Mahmoud AbuElhija; Pirjo Pakarinen; Ilpo Huhtaniemi; Amin A Momin; Jing Wang; David N Stivers; Zhilin Liu; Marvin L Meistrich
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-08
Journal Detail:
Title:  Biology of reproduction     Volume:  85     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2012-02-15     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  823-33     Citation Subset:  IM    
Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77025, USA.
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MeSH Terms
Androgen Antagonists / therapeutic use
Crosses, Genetic
Drug Therapy, Combination
Estradiol / therapeutic use*
Estrogens / therapeutic use*
Flutamide / therapeutic use
Gamma Rays
Gene Expression Regulation / drug effects*,  radiation effects
Gonadotropin-Releasing Hormone / antagonists & inhibitors
Hormone Antagonists / therapeutic use
Insulin / genetics,  metabolism
MicroRNAs / metabolism
Oligonucleotide Array Sequence Analysis
Oligopeptides / therapeutic use
Proteins / genetics,  metabolism
Rats, Inbred BN
Rats, Inbred Lew
Spermatogenesis / drug effects*,  radiation effects*
Testis / drug effects*,  metabolism*,  pathology,  radiation effects
Testosterone / antagonists & inhibitors
Grant Support
Reg. No./Substance:
0/Androgen Antagonists; 0/Estrogens; 0/Hormone Antagonists; 0/Insulin; 0/Leydig insulin-like protein; 0/MicroRNAs; 0/Oligopeptides; 0/Proteins; 13311-84-7/Flutamide; 170157-13-8/acyline; 33515-09-2/Gonadotropin-Releasing Hormone; 50-28-2/Estradiol; 58-22-0/Testosterone
Comment In:
Biol Reprod. 2011 Oct;85(4):647-9   [PMID:  21849707 ]

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