Hormonal regulation of testicular steroid and cholesterol homeostasis

Stephen Eacker, Nalini Agrawal, Kun Qian, Helén L. Dichek, Eun Yeung Gong, Keesook Lee, Robert E. Braun

Research output: Contribution to journalArticle

Abstract

The male sex steroid, testosterone (T), is synthesized from cholesterol in the testicular Leydig cell under control of the pituitary gonadotropin LH. Unlike most cells that use cholesterol primarily for membrane synthesis, steroidogenic cells have additional requirements for cholesterol, because it is the essential precursor for all steroid hormones. Little is known about how Leydig cells satisfy their specialized cholesterol requirements for steroid synthesis. We show that in mice with a unique hypomorphic androgen mutation, which disrupts the feedback loop governing T synthesis, that genes involved in cholesterol biosynthesis/uptake and steroid biosynthesis are up-regulated. We identify LH as the central regulatory molecule that controls both steroidogenesis and Leydig cell cholesterol homeostasis in vivo. In addition to the primary defect caused by high levels of LH, absence of T signaling exacerbates the lipid homeostasis defect in Leydig cells by eliminating a short feedback loop. We show that T signaling can affect the synthesis of steroids and modulates the expression of genes involved in de novo cholesterol synthesis. Surprisingly, accumulation of active sterol response element-binding protein 2 is not required for up-regulation of genes involved in cholesterol biosynthesis and uptake in Leydig cells.

Original languageEnglish (US)
Pages (from-to)623-635
Number of pages13
JournalMolecular Endocrinology
Volume22
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

Homeostasis
Steroids
Cholesterol
Leydig Cells
Pituitary Gonadotropins
Response Elements
Sterols
Androgens
Genes
Testosterone
Carrier Proteins
Up-Regulation
Hormones
Lipids
Gene Expression
Mutation
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Eacker, S., Agrawal, N., Qian, K., Dichek, H. L., Gong, E. Y., Lee, K., & Braun, R. E. (2008). Hormonal regulation of testicular steroid and cholesterol homeostasis. Molecular Endocrinology, 22(3), 623-635. https://doi.org/10.1210/me.2006-0534

Hormonal regulation of testicular steroid and cholesterol homeostasis. / Eacker, Stephen; Agrawal, Nalini; Qian, Kun; Dichek, Helén L.; Gong, Eun Yeung; Lee, Keesook; Braun, Robert E.

In: Molecular Endocrinology, Vol. 22, No. 3, 03.2008, p. 623-635.

Research output: Contribution to journalArticle

Eacker, S, Agrawal, N, Qian, K, Dichek, HL, Gong, EY, Lee, K & Braun, RE 2008, 'Hormonal regulation of testicular steroid and cholesterol homeostasis', Molecular Endocrinology, vol. 22, no. 3, pp. 623-635. https://doi.org/10.1210/me.2006-0534
Eacker, Stephen ; Agrawal, Nalini ; Qian, Kun ; Dichek, Helén L. ; Gong, Eun Yeung ; Lee, Keesook ; Braun, Robert E. / Hormonal regulation of testicular steroid and cholesterol homeostasis. In: Molecular Endocrinology. 2008 ; Vol. 22, No. 3. pp. 623-635.
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