The effect of γ-linolenic acid on Polycystic Ovary Syndrome associated Focal Segmental Glomerulosclerosis via TGF-ß pathway.

BACKGROUND: In recent years, female infertility from Polycystic Ovary Syndrome (PCOS) has gained scientific interest. PCOS alters the metabolic and endocrine functioning in females. The elevation in androgens can damage the androgen receptors present on the kidney giving rise to renal disorders like Focal Segmental Glomerulosclerosis (FSGS). Transforming Growth Factor Beta (TGF-ß) in the ovary is activated by activin for Follicle Stimulating Hormone (FSH) secretion and in the kidney by thrombospondin 1 (TSP1) for cell growth and apoptosis. Studies show that gamma-linolenic acid (GLA) effectively treats breast cancer, eczema, inflammatory conditions and PCOS. AIM: The study aimed to find out the possibility of FSGS development in PCOS and to understand the effect of GLA on FSGS via the TGF-ß pathway. METHOD: To carry out the study, the dehydroepiandrosterone (DHEA) induced PCOS model was used. Three groups namely vehicle control, DHEA, and DHEA+GLA, were used with six animals in each. TGF-ß1, TGF-ß2, and TSP1 genes were studied using real-time PCR. RESULTS: The study showed an increase in the level of renal fibrosis biomarker, TSP1, in the DHEA group, which was further decreased by an anti-inflammatory agent, GLA. The TGF-ß1 and TGF-ß2 genes associated with the TGF-ß pathway were seen to be increased in DHEA-induced PCOS rats which showed a possible relation between the two conditions. CONCLUSION: The study shows a possible development of renal fibrosis in the DHEA-induced PCOS model. The GLA might act as a ligand to regulate TGF-ß signaling in glomerulosclerosis in a DHEA-induced PCOS model.

Role of TGF-ß signalling in PCOS associated focal segmental glomerulosclerosis.

Research on polycystic ovarian syndrome (PCOS) remains intense due to its evolving impact on metabolism, reproduction and cardiovascular function. Changes in metabolic pathways can also significantly impact renal function including the development of Focal Segmental Glomerulosclerosis (FSGS), one of the most highly investigated renal diseases. In FSGS, scarring of the glomerulus vascular tuft damages the kidneys. Onset of FSGS may either be congenital or due to other disorders that affect the metabolism and normal kidney function. Both PCOS and FSGS appear to be associated with Transforming Growth Factor-ß (TGF-ß) signalling. Over-expression of TGF-ß may be due to the activation of the thrombospondin 1 (TSP1) gene, which increases the probability of developing renal disorders. Higher androgen levels in PCOS may also cause podocyte damage thus directly impacting development of FSGS. This article reviews the role of TGF-ß's in PCOS and FSGS and explores the inter-relationship between these two disorders.