The effects of levonorgestrel on FSH-stimulated primary rat granulosa cell cultures through gene expression profiling are associated to hormone and folliculogenesis processes

• Published in: Molecular and cellular endocrinology 2017-01, Vol.439, p.337-345
• Main Authors: Lira-Albarrán, Saúl, Larrea-Schiavon, Marco F., González, Leticia, Durand, Marta, Rangel, Claudia, Larrea, Fernando
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Contraception; Down-Regulation - genetics; Estradiol - biosynthesis; Estrogens - biosynthesis; Female; Follicle Stimulating Hormone - pharmacology; Gene Expression Profiling; Gene transcription; Granulosa cells; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Levonorgestrel; Levonorgestrel - pharmacology; Multigene Family; Oligonucleotide Array Sequence Analysis; Organogenesis - drug effects; Organogenesis - genetics; Progesterone - pharmacology; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Signal Transduction - drug effects; Signal Transduction - genetics; Up-Regulation - genetics
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2016.09.020

Levonorgestrel (LNG), a synthetic progestin, is used in emergency contraception (EC). The mechanism is preventing or delaying ovulation at the level of the hypothalamic pituitary unit; however, little knowledge exists on LNG effects at the ovary. The aim of this study was to identify the effects of LNG on FSH-induced 17β-estradiol (E2) production, including LNG-mediated changes on global gene expression in rat granulosa cells (GC). Isolated GC from female Wistar rats were incubated in vitro in the presence or absence of human FSH and progestins. At the end of incubations, culture media and cells were collected for E2 and mRNA quantitation. The results showed the ability of LNG to inhibit both hFSH-induced E2 production and aromatase gene expression. Microarray analysis revealed that LNG treatment affects GC functionality particularly that related to folliculogenesis and steroid metabolism. These results may offer additional evidence for the mechanisms of action of LNG as EC. •Levonorgestrel inhibited hFSH-induced estradiol biosynthesis in rat granulosa cells.•The mechanism of aromatase inhibition is post-cAMP at the level of gene transcription.•Levonorgestrel alters FSH-responsive genes involved in folliculogenesis.•Progesterone-mediated oocyte maturation genes are modified by levonorgestrel.•The ovary is a target for levonorgestrel contraceptive effects.