Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice.

In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism.

Androgen-induced epigenetic modulations in the ovary.

In recent years, androgens have emerged as critical regulators of female reproduction and women's health in general. While high levels of androgens in women are associated with polycystic ovary syndrome (PCOS), recent evidence suggests that a certain amount of direct androgen action through androgen receptor is also essential for normal ovarian function. Moreover, prenatal androgen exposure has been reported to cause developmental reprogramming of the fetus that manifests into adult pathologies, supporting the Developmental Origins of Health and Disease (DOHaD) hypothesis.

Bis-Quinolinium Cyclophane Blockers of SK Potassium Channels Are Antagonists of M3 Muscarinic Acetylcholine Receptors.

Dequalinium is used as an antimicrobial compound for oral health and other microbial infections. Derivatives of dequalinium, the bis-quinolinium cyclophanes UCL 1684 and UCL 1848, are high affinity SK potassium channel antagonists. Here we investigated these compounds as M3 muscarinic receptor (mACHR) antagonists.