Macrophage secretions modulate the steroidogenesis of polycystic ovary in rats: Effect of testosterone on macrophage pro-inflammatory cytokines

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• 作者：Florencia Figueroa^a ; Roberto Davicino^b ; Blas Micalizzi^b ; Liliana Oliveros^a ; Myriam Forneris^a ; ^{mforn@unsl.edu.ar}
• 关键词：Polycystic ovary ; Estradiol valerate ; Macrophages ; Tumor necrosis factor alpha ; Nitric oxide ; Interleukin-6
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：22 May, 2012
• 卷：90
• 期：19-20
• 页码：733-739
• 文件大小：845 K

摘要

Aims

The macrophage secretions' effect on ovarian steroidogenesis is investigated in a polycystic ovary syndrome rat model (PCO rat). The influence of testosterone environment on the expression of macrophage pro-inflammatory cytokines that participate in ovarian steroidogenesis is studied.

Main methods

PCO rats were induced by estradiol valerate. Spleen macrophages were cultured with and without testosterone (10^鈭?#xA0;6 M) and their secretions were used to stimulate ovaries from PCO and control rats. Ovarian hormones released and ovary mRNA levels of P450 aromatase and 3尾-hydroxysteroid dehydrogenase were measured by radioimmunoassay and RT-PCR, respectively. The tumor necrosis factor alpha (TNF伪) and nitric oxide (NO) levels in macrophage culture medium, along with the TNF伪, interleukin (IL)-6, IL-10 and androgen receptors (AR) mRNA levels in macrophage cells were determined.

Key findings

Macrophages from PCO rats released more TNF伪 and NO, expressed higher TNF伪 and IL-6, lower AR, and no change in IL-10 mRNA levels than control macrophages. TNF伪, IL-6 and AR changes were greater after macrophage testosterone treatment. Macrophage secretions from PCO rats stimulated androstenedione and decreased estradiol release and ovarian mRNA P450 aromatase expression in PCO rats compared to macrophage secretions from control rats.

These effects were greater when macrophages from PCO rats were treated with testosterone. Ovarian progesterone response was unchanged.

Significance

The differential steroidogenic ability of macrophage secretions from PCO rats is associated to the in vitro testosterone environment. Testosterone, probably acting on macrophage AR, induces a greater release of TNF伪, modifying ovarian response by increasing androstenedione and slightly decreasing estradiol without affecting progesterone.