The leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult leydig cells and for fertility

Soichi Yamashita, Ping Tai, Jean Charron, Che Myong Ko, Mario Ascoli

Research output: Contribution to journalArticle

Abstract

MAPK kinase (MEK)1 and MEK2 were deleted from Leydig cells by crossing Mek1f/f;Mek2-/- and Cyp17iCre mice. Primary cultures of Leydig cell from mice of the appropriate genotype (Mek1f/f; Mek2-/-;iCre+) show decreased, but still detectable, MEK1 expression and decreased or absent ERK1/2 phosphorylation when stimulated with epidermal growth factor, Kit ligand, cAMP, or human choriogonadotropin (hCG). The body or testicular weights of Mek1f/f;Mek2-/-;iCre+ mice are not significantly affected, but the testis have fewer Leydig cells. The Leydig cell hypoplasia is paralleled by decreased testicular expression of several Leydig cell markers, such as the lutropin receptor, steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, 17α- hydroxylase, and estrogen sulfotransferase. The expression of Sertoli or germ cell markers, as well as the shape, size, and cellular composition of the seminiferous tubules, are not affected. cAMP accumulation in response to hCG stimulation in primary cultures of Leydig cells from Mek1f/f; Mek2-/-;iCre+ mice is normal, but basal testosterone and testosterone syntheses provoked by addition of hCG or a cAMP analog, or by addition of substrates such as 22-hydroxycholesterol or pregnenolone, are barely detectable. The Mek1f/f;Mek2-/-;iCre+ males show decreased intratesticular testosterone and display several signs of hypoandrogenemia, such as elevated serum LH, decreased expression of two renal androgen-responsive genes, and decreased seminal vesicle weight. Also, in spite of normal sperm number and motility, the Mek1f/f;Mek2-/-;iCre+ mice show reduced fertility. These studies show that deletion of MEK1/2 in Leydig cells results in Leydig cell hypoplasia, hypoandrogenemia, and reduced fertility.

Original languageEnglish (US)
Pages (from-to)1211-1222
Number of pages12
JournalMolecular Endocrinology
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Fingerprint

MAP Kinase Signaling System
Leydig Cells
Fertility
Chorionic Gonadotropin
Population
Testosterone
MAP Kinase Kinase 1
Cholesterol Side-Chain Cleavage Enzyme
LH Receptors
Weights and Measures
Pregnenolone
Seminiferous Tubules
Stem Cell Factor
Sperm Count
Seminal Vesicles
Sertoli Cells
Sperm Motility
Mitogen-Activated Protein Kinase Kinases
Mixed Function Oxygenases
Epidermal Growth Factor

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

The leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult leydig cells and for fertility. / Yamashita, Soichi; Tai, Ping; Charron, Jean; Ko, Che Myong; Ascoli, Mario.

In: Molecular Endocrinology, Vol. 25, No. 7, 01.07.2011, p. 1211-1222.

Research output: Contribution to journalArticle

Yamashita, Soichi ; Tai, Ping ; Charron, Jean ; Ko, Che Myong ; Ascoli, Mario. / The leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult leydig cells and for fertility. In: Molecular Endocrinology. 2011 ; Vol. 25, No. 7. pp. 1211-1222.
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