Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function.
Steroid biosynthesis in ovary is enhanced by the orphan nuclear receptor, steroidogenic factor-1 (SF-1); however, we reported that liver receptor homolog-1 (LRH-1), a closely related receptor to SF-1, is also expressed in mouse ovary. To further investigate the role of LRH-1 in mouse ovary, we used in situ hybridization to identify the cell types that express LRH-1 versus SF-1, and carried out functional studies to determine the role of LRH-1 in the regulation of the human (h) ovary-specific CYP19 promoter. LRH-1 expression was found to be abundant and highly restricted to cells involved in estrogen biosynthesis-granulosa cells during the estrous cycle, and in corpora lutea (CL) of pregnancy. In contrast, SF-1 was expressed most highly in C(19)-steroid-producing theca cells and interstitium, and at low levels in granulosa and luteal cells. Transfection studies using granulosa cells demonstrated that LRH-1 is a potent regulator of both basal and forskolin-induced transcription of the ovary-specific hCYP19 promoter. This activity was dependent upon two nuclear receptor half-sites within the proximal hCYP19 promoter. Based on these findings, we propose that LRH-1 plays an important role as a competence factor in regulating aromatase, and thus estrogen biosynthesis, in ovary.
Hinshelwood
Margaret M
MM
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9038, USA. mhinshelwood@biochem.swmed.edu
Repa
Joyce J
JJ
Shelton
John M
JM
Richardson
James A
JA
Mangelsdorf
David J
DJ
Mendelson
Carole R
CR
D000818:Animals; D001141:Aromatase / Q000235:genetics; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D003338:Corpus Luteum / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008184:Luteal Cells / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D054339:Steroidogenic Factor 1; D013799:Theca Cells / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; C515057:NR5A1 protein, human; C431936:Nr5a2 protein, mouse; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C083666:Son protein, mouse; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D005576:Colforsin; D000242:Cyclic AMP; D001141:Aromatase