TY - JOUR
T1 - Expression of LRH-1 and SF-1 in the mouse ovary
T2 - Localization in different cell types correlates with differing function
AU - Hinshelwood, Margaret M.
AU - Repa, Joyce J.
AU - Shelton, John M.
AU - Richardson, James A.
AU - Mangelsdorf, David J.
AU - Mendelson, Carole R.
N1 - Funding Information:
This research was supported by NIH 5-R01-DK31206 as well as an Obstetrics/Gynecology Basic Research Fund. The authors also wish to thank Dr Mala Mahendroo for her assistance with the timed pregnant mice and Jeffrey Stark, Chris Pomajzl and David Sutcliffe for their assistance with histology.
PY - 2003/9/30
Y1 - 2003/9/30
N2 - 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.
AB - 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.
KW - Aromatase
KW - Granulosa cell
KW - LRH-1
KW - Luteal cell
KW - Ovary
KW - SF-1
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U2 - 10.1016/S0303-7207(03)00257-0
DO - 10.1016/S0303-7207(03)00257-0
M3 - Article
C2 - 12972182
AN - SCOPUS:0042335826
SN - 0303-7207
VL - 207
SP - 39
EP - 45
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -