title: Interleukin-6 inhibits adrenal androgen release from bovine adrenal zona reticularis cells by inhibiting the expression of steroidogenic proteins.
abstract: Interleukin-6 (IL-6) is secreted by adrenocortical cells and modifies cortisol secretion. In this study, the effects of IL-6 on adrenal androgen release were investigated. The zona reticularis (ZR) was generally isolated from bovine adrenal glands by dissection. In select experiments, the intact adrenal cortex (ie, all 3 adrenocortical zones) was dissected from the adrenal glands. For androgen release experiments, ZR and intact adrenocortical cubes were dispersed into isolated cells, the cells cultured and exposed to IL-6 and/or adrenocorticotropic hormone (ACTH), and androgen release determined by radioimmunoassay. Basal and ACTH-stimulated androgen release from the ZR was inhibited by IL-6 in a concentration-dependent (10-1000 pg/mL) and time-dependent (4-24 h) manner (P < 0.01 by 1-way analysis of variance and the Bonferroni test). In contrast, IL-6 increased basal and ACTH-stimulated androgen release from mixed adrenocortical cells (P < 0.01). The mechanism of IL-6 inhibition of androgen release was investigated by exposing ZR strips to IL-6 and measuring the expression of the messenger RNA (mRNA) and protein of steroidogenic factors. Basal and ACTH-stimulated expression of the mRNA and protein for steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, 3-β-hydroxysteroid dehydrogenase type 2, steroid 17-α-hydroxylase/17,20 lyase/17,20 desmolase, and the nuclear factor steroidogenic factor 1 (SF-1), that stimulates steroidogenesis, were decreased by IL-6 (P < 0.01). In contrast IL-6 increased the mRNA and protein for dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1), a nuclear factor that inhibits steroidogenesis (P < 0.01). In summary, IL-6 decreased androgen release and the expression of steroidogenic factors in the ZR, and this decrease may be mediated in part through increasing DAX-1 and decreasing SF-1.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: S
authors.initials: S
authors.lastname: McIlmoil
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Call
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: M
authors.initials: M
authors.lastname: Barney
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: J
authors.initials: J
authors.lastname: Strickland
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA. Electronic address: allan_judd@byu.edu.
authors.forename: A M
authors.initials: AM
authors.lastname: Judd
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002417:Cattle / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015850:Interleukin-6 / Q000494:pharmacology*; D015385:Zona Reticularis / Q000166:cytology*
chemical_list: D000728:Androgens; D015850:Interleukin-6
keywords: Adrenal; Androgen; Cytokine; Interleukin-6; Steroidogenesis