A proportion of women with polycystic ovary syndrome (PCOS) are overweight or obese. PCOS affects 5–20% of women of reproductive age, and is characterised by anovulation, menstrual irregularities, insulin resistance and hyperandrogenism.

In this study, Khan et al. investigated the effects of exendin-4 (Ex-4) and peptide YY (PYY) on reproductive function in mice fed a high-fat diet (HFD). Both peptides reduced blood glucose and energy intake without affecting body weight. Ex-4 increased the frequency of metoestrus and decreased that of dioestrus, eliminating repeated dioestrus and acyclicity in treated mice. Luteinising hormone levels were elevated in both Ex-4 and PYY groups, compared with controls. Changes in adrenal morphology induced by the HFD, such as reduced capsule and zona glomerulosa thickness, were reversed by peptide treatments. In the ovaries, the HFD increased atretic follicles, an effect that was mitigated by Ex-4 and PYY. Ex-4 also enhanced the formation of corpora lutea due to prolonged metoestrus. Gene expression analysis revealed altered insulin receptor and progesterone receptor expression in the adrenals, with Ex-4 downregulating the glucagon-like peptide-1 receptor (GLP-1R), and PYY affecting Prgtr expression in both the adrenals and the ovaries.

These findings suggest that modulating GLP-1R and neuropeptide Y2 receptor (NPY2R) can influence reproductive physiology, with potential direct effects on ovarian and adrenal function in female mice.

Read the full article in Journal of Endocrinology 264 e240189 https://doi.org/10.1530/JOE-24-0189