Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by...

Area of Science:

• Reproductive Biology
• Steroidogenesis
• Gynaecological Oncology

Background:

• Human ovarian surface epithelium (HOSE) is susceptible to gynaecological diseases like endometriosis and ovarian cancer.
• Steroid signaling is crucial for HOSE regulation, potentially influenced by ovulation-related injury-repair cycles.

Purpose of the Study:

• To investigate the steroidogenic gene expression profile of HOSE cells.
• To determine the impact of interleukin-1alpha (IL-1alpha) on HOSE gene expression, particularly concerning steroidogenesis and inflammation.

Main Methods:

• Utilized a custom microarray to analyze over 250 genes involved in steroid hormone, sterol, and retinoid pathways in cultured HOSE cells.
• Treated HOSE cells with IL-1alpha and assessed gene expression changes using microarray and quantitative reverse-transcription PCR (qRT-PCR).
• Verified gene expression results for selected genes using qRT-PCR.

Main Results:

• Untreated HOSE cells expressed genes for de novo cholesterol and C21/C19 steroid biosynthesis, but not for glucocorticoids, estrogens, or 5α-reduced androgens.
• IL-1alpha significantly upregulated 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) and several inflammation-associated genes (e.g., IL-6, IL-8, NFkappaB inhibitor alpha).
• IL-1alpha significantly suppressed 3betaHSD1 and other genes including aldehyde dehydrogenases (ALDH) and nuclear receptors.

Conclusions:

• Cultured HOSE cells possess a distinct steroidogenic phenotype.
• IL-1alpha coordinately induces 11betaHSD1 and glucocorticoid-regulated inflammatory genes in HOSE cells.
• Cortisol generated by 11betaHSD1 may play a role in resolving inflammation in the human ovarian surface epithelium.