Submitted on August 2, 2006
Revised on August 18, 2006
Accepted on August 23, 2006
Low-density lipoprotein and cAMP cooperate to regulate expression and function of the low-density lipoprotein receptor-related protein in rat ovarian granulosa cells
Salman Azhar, Satyanarayana Medicherla, Wen-Jun Shen, Yoshio Fujioka, Loren G. Fong, Eve Reaven, and Allen D. Cooper
Gerontology, Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304
Corresponding Author: salman.azhar{at}med.va.gov
Rat ovarian granulosa rely heavily on lipoprotein-derived cholesterol for steroidogenesis, which is principally supplied by the LDL receptor- and SR-BI-mediated pathways. In the current study, we characterized the hormonal and cholesterol regulation of another member of the LDL receptor superfamily, LRP and its role in granulosa cell steroidogenesis. Co-incubation of cultured granulosa cells with LDL and Bt2cAMP greatly increased the mRNA/protein levels of LRP. Bt2cAMP and Bt2cAMP + hLDL also enhanced SR-BI mRNA levels. However, there was no change in the expression of RAP, a chaperone for LRP, or another lipoprotein receptor, LRP8/apoER2 in response to Bt2cAMP + hLDL, whereas the mRNA expression of LDL receptor was significantly reduced. The induced LRP was fully functional, mediating increased uptake of its ligand, 2-macroglobulin. The level of binding of another LRP ligand, chylomicron remnants, did not increase, although the extent of remnants degradation that could be attributed to the LRP doubled in cells with the elevated levels of LRP. The addition of lipoprotein type LRP ligands such as chylomicron remnants and VLDL to incubation medium significantly increased the progestin production in both under basal and stimulated conditions. In summary, our studies demonstrate a role for LRP in lipoprotein-supported ovarian granulosa cell steroidogenesis.
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