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Increased, secretion of LH from anterior pituitary leads to Increased, Steroidogenic acute regulatory protein (StAR)
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Hypothalamic estrogen receptors inhibition leading to ovarian cancer||adjacent||High||Moderate||Kalyan Gayen (send email)||Under development: Not open for comment. Do not cite||Under Development|
Life Stage Applicability
|Adult, reproductively mature||High|
Key Event Relationship Description
The activity of StAR protein in theca cells is control by LH (Murayama et al., 2012). Subsequently, StAR protein regulates cholesterol transportation to the mitochondria and therefore, the production of steroid hormones is regulated by StAR protein (Clark and Stocco, 1995).
Evidence Collection Strategy
Evidence Supporting this KER
- Murayama et al. studied the in vitro LH pulse dose in Bovine ovaries and reported LH dose enhances the activity of StAR protein (Murayama et al., 2012).
- Johnson and Bridgham performed in vitro studied in granulosa cells from prehierarchal and preovulatory hen follicles to examine the regulation of steroidogenic acute regulatory protein (StAR) by LH. They reported the treatment with LH rapidly increased StAR mRNA and protein (Johnson and Bridgham, 2001).
In mammalian species (e.g., rat,rabbit, human), LH stimulates the StAR protein to increase the cholesterol transport in to the inner mitochondrial membrane. Cholesterol is the precursor of sex hormones. Therefore, LH regulate the steroidogenic function of theca cells (Murayama et al., 2012; Johnson and Bridgham, 2001; Rekawiecki et al., 2005).
Uncertainties and Inconsistencies
No uncertainties and inconsistencies are observed
Known modulating factors
Time scale for the response between LH to StAR protein in hours (3-20 h) (Johnson and Bridgham, 2001; Martinat et al., 2005; Rekawiecki et al., 2005).
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Clark, B. J., & Stocco, D. M. (1995). Expression of the steroidogenic acute regulatory (StAR) protein: a novel LH-induced mitochondrial protein required for the acute regulation of steroidogenesis in mouse Leydig tumor cells. Endocr Res, 21(1-2), 243-57. doi:10.3109/07435809509030440.
Eacker, S. M., Agrawal, N., Qian, K., Dichek, H. L., Gong, E. Y., Lee, K., et al. (2008). Hormonal regulation of testicular steroid and cholesterol homeostasis. Mol Endocrinol, 22(3), 623-35.
Johnson, A. L., & Bridgham, J. T. (2001). Regulation of steroidogenic acute regulatory protein and luteinizing hormone receptor messenger ribonucleic acid in hen granulosa cells. Endocrinology, 142(7), 3116-24.
Liu, T., Wimalasena, J., Bowen, R. L., & Atwood, C. S. (2007). Luteinizing hormone receptor mediates neuronal pregnenolone production via up-regulation of steroidogenic acute regulatory protein expression. J Neurochem. , 100(5), 1329-39.
Martinat, N., Crepieux, P., Reiter, E., & Guillou, F. (2005). Extracellular signal-regulated kinases (ERK) 1, 2 are required for luteinizing hormone (LH)-induced steroidogenesis in primary Leydig cells and control steroidogenic acute regulatory (StAR) expression. Reprod Nutr Dev, 45(1), 101-8. doi:10.1051/rnd:2005007.
Murayama, C., Miyazaki, H., Miyamoto, A., & Shimizu, T. (2012). Luteinizing hormone (LH) regulates production of androstenedione and progesterone via control of histone acetylation of StAR and CYP17 promoters in ovarian theca cells. Mol Cell Endocrinol, 350(1), 1-9. doi:S0303-7207(11)00677-0 [pii]10.1016/j.mce.2011.11.014.
Rekawiecki, R., Nowik, M., & Kotwica, J. (2005). Stimulatory effect of LH, PGE2 and progesterone on StAR protein, cytochrome P450 cholesterol side chain cleavage and 3beta hydroxysteroid dehydrogenase gene expression in bovine luteal cells. Prostaglandins Other Lipid Mediat, 78(1-4), 169-84. doi:S1098-8823(05)00080-8 [pii]10.1016/j.prostaglandins.2005.06.009.
Tsang, B. K., Armstrong, D. T., & Whitfield, J. F. (1980). Steroid biosynthesis by isolated human ovarian follicular cells in vitro. J Clin Endocrinol Metab. , 51(6), 1407-11.
Tsuchiya, M., Inoue, K., Matsuda, H., Nakamura, K., Mizutani, T., Miyamoto, K., et al. (2003). Expression of steroidogenic acute regulatory protein (StAR) and LH receptor in MA-10 cells. Life Sciences, 73(22), 2855-2863. doi:https://doi.org/10.1016/S0024-3205(03)00698-2.