Estrogen regulates development of the somatic cell phenotype in the eutherian ovary.
Steroids play a critical role in gonadal differentiation in birds, reptiles, and amphibia whereas gonadal differentiation in mammals is thought to be determined by genetic mechanisms. The gonads of female mice incapable of synthesizing estrogens due to disruption of the aromatase gene (ArKO) provide a unique model to test the role of estrogen in regulating the gonadal phenotype. We have shown that in the absence of estrogen, genetically female mice develop testicular tissue within their ovaries. The ovaries develop cells that possess structural and functional characteristics of testicular interstitial cells and of seminiferous tubule-like structures lined with Sertoli cells. Moreover, the ovaries express mRNA for the testis-specific Sertoli cell transcription factor Sox 9 and espin protein, which is specific for inter-Sertoli cell junctions. The development of the testicular tissue in this model can be reverted/postponed by replacing estrogen. When ArKO female mice were fed a diet containing phytoestrogens, the appearance of Leydig and Sertoli cells was postponed and reduced. Furthermore, administration of estradiol-17beta decreased the number of Sertoli and Leydig cells in the ovaries. These findings constitute definitive evidence that estrogen plays a critical role in maintaining female somatic interstitial and granulosa cells in the eutherian ovary.
Britt
Kara L
KL
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia. kara.britt@med.monash.edu.au
Kerr
Jeff
J
O'Donnell
Liza
L
Jones
Margaret E E
ME
Drummond
Ann E
AE
Davis
Susan R
SR
Simpson
Evan R
ER
Findlay
Jock K
JK
D000818:Animals; D001141:Aromatase / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006107:Granulosa Cells / Q000648:ultrastructure; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D007529:Isoflavones; D007985:Leydig Cells / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000032:analysis / Q000276:immunology; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger / Q000096:biosynthesis; D055758:SOX9 Transcription Factor; D012708:Sertoli Cells / Q000648:ultrastructure; D013737:Testis / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D006062:Gonadotropins; D006609:High Mobility Group Proteins; D007529:Isoflavones; D008840:Microfilament Proteins; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; C104108:espin protein, mouse; D004958:Estradiol; D001141:Aromatase