TY - JOUR
T1 - Differential regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells
T2 - Role of SR-B1-mediated selective cholesteryl ester transport
AU - Rao, Rekha M.
AU - Jo, Youngah
AU - Leers-Sucheta, Susan
AU - Bose, Himangshu S.
AU - Miller, Walter L.
AU - Azhar, Salman
AU - Stocco, Douglas M.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - The rat R2C Leydig tumor cell line is constitutively steroidogenic in nature, while the mouse MA-10 Leydig tumor cell line synthesizes large amounts of steroids only in response to hormonal stimulation. Earlier studies showed abundant cAMP-independent steroid production and constitutive expression of steroidogenic acute regulatory (StAR) protein in R2C cells. The objective of the current study was to identify possible genetic alterations in the R2C 112C cell line responsible for rendering it a constitutively steroidogenic cell line, especially those that might have altered its cholesterol homeostatic mechanisms. Measurement of the levels of cholesterol esters and free cholesterol, precursors for steroidogenesis, indicated that R2C mitochondria were fourfold enriched in free cholesterol content compared with MA-10 mitochondria. In addition to the previously demonstrated increased expression of StAR protein, we show that R2C cells possess marginally enhanced protein kinase A activity, exhibit higher capacity to take up extracellular cholesterol esters, and express much higher levels of scavenger receptor-type B class 1 (SR-B1) and hormone sensitive lipase (HSL). These observations suggest that the high level of steroid biosynthesis in R2C cells is a result of the constitutive expression of the components involved in the uptake of cholesterol esters (SR-B1), their conversion to free cholesterol (HSL), and its mobilization to the inner mitochondrial membrane (StAR).
AB - The rat R2C Leydig tumor cell line is constitutively steroidogenic in nature, while the mouse MA-10 Leydig tumor cell line synthesizes large amounts of steroids only in response to hormonal stimulation. Earlier studies showed abundant cAMP-independent steroid production and constitutive expression of steroidogenic acute regulatory (StAR) protein in R2C cells. The objective of the current study was to identify possible genetic alterations in the R2C 112C cell line responsible for rendering it a constitutively steroidogenic cell line, especially those that might have altered its cholesterol homeostatic mechanisms. Measurement of the levels of cholesterol esters and free cholesterol, precursors for steroidogenesis, indicated that R2C mitochondria were fourfold enriched in free cholesterol content compared with MA-10 mitochondria. In addition to the previously demonstrated increased expression of StAR protein, we show that R2C cells possess marginally enhanced protein kinase A activity, exhibit higher capacity to take up extracellular cholesterol esters, and express much higher levels of scavenger receptor-type B class 1 (SR-B1) and hormone sensitive lipase (HSL). These observations suggest that the high level of steroid biosynthesis in R2C cells is a result of the constitutive expression of the components involved in the uptake of cholesterol esters (SR-B1), their conversion to free cholesterol (HSL), and its mobilization to the inner mitochondrial membrane (StAR).
KW - Cyclic adenosine monophosphate
KW - Leydig cells
KW - Progesterone
KW - Steroid hormones
KW - Testis
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U2 - 10.1095/biolreprod.102.007518
DO - 10.1095/biolreprod.102.007518
M3 - Article
C2 - 12493702
AN - SCOPUS:0037230367
SN - 0006-3363
VL - 68
SP - 114
EP - 121
JO - Biology of reproduction
JF - Biology of reproduction
IS - 1
ER -