Differential regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells: Role of SR-B1-mediated selective cholesteryl ester transport

Rekha M. Rao, Youngah Jo, Susan Leers-Sucheta, Himangshu S. Bose, Walter L. Miller, Salman Azhar, Douglas M. Stocco

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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).

Original languageEnglish (US)
Pages (from-to)114-121
Number of pages8
JournalBiology of Reproduction
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

CD36 Antigens
Leydig Cell Tumor
Cholesterol Esters
Steroids
Cholesterol
Hormones
Sterol Esterase
Tumor Cell Line
Mitochondria
Cell Line
Mitochondrial Membranes
Cyclic AMP-Dependent Protein Kinases
steroidogenic acute regulatory protein

Keywords

  • Cyclic adenosine monophosphate
  • Leydig cells
  • Progesterone
  • Steroid hormones
  • Testis

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Differential regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells : Role of SR-B1-mediated selective cholesteryl ester transport. / Rao, Rekha M.; Jo, Youngah; Leers-Sucheta, Susan; Bose, Himangshu S.; Miller, Walter L.; Azhar, Salman; Stocco, Douglas M.

In: Biology of Reproduction, Vol. 68, No. 1, 01.01.2003, p. 114-121.

Research output: Contribution to journalArticle

Rao, Rekha M. ; Jo, Youngah ; Leers-Sucheta, Susan ; Bose, Himangshu S. ; Miller, Walter L. ; Azhar, Salman ; Stocco, Douglas M. / Differential regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells : Role of SR-B1-mediated selective cholesteryl ester transport. In: Biology of Reproduction. 2003 ; Vol. 68, No. 1. pp. 114-121.
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