Research Projects

Rationale: Polyamines have been shown to regulate the neuroendocrine axis and glucose transport; anti-polyamine, eflornithine, is a major constituent of Vaniqa, a drug used to treat hirsutism, a condition closely associated with polycystic ovarian syndrome (PCOS). Putrescine, a polyamine, has been recently shown by the PI’s group to manage PCOS-like conditions in the PCOS-like hyperandrogenized mice model, and it induces fertility in them (data unpublished). Also, it has been found out that there is differential regulation of genes associated with polyamine metabolism in the granulosa cells of PCOS subjects’ vs control using PCOS RNA seq data and a pilot work from PI’s group showed circulatory levels of putrescine and spermidine, polyamines, to be significantly low in PCOS subjects as compared to control ones (data unpublished). Homocysteine, S-adenosylmethionine (SAM) and polyamines are obtained from methionine metabolism, and are biochemically interrelated through methylation and one-carbon metabolism pathways. SAM is a methyl donor cum mediator between polyamines and homocysteine. Homocysteine metabolism is closely associated with polyamine metabolism with SAM as an important intermediate metabolite. A precursor for decarboxylated SAM (dcSAM), is required in polyamine biosynthesis. Reports suggest that PCOS subjects have increased homocysteine levels, and promoters of genes in PCOS ovaries are hypomethylated, particularly in specific genes related to hormonal regulation, metabolism, and inflammatory responses. Gaps: Till now there exists no report showing whether altered polyamine metabolism affects homocysteine levels and reproductive status in normal and PCOS condition; or if polyamine/ SAM treatment can improve the hypomethylation and hyperhomocysteinemia scenario in PCOS has not been explored yet; this might ameliorate PCOS condition. Also, the scenario of homocysteine, SAM and polyamines in Indian PCOS subjects are not yet known, knowledge if gained might open new strategy for PCOS management. Also, the effect of SAM on PCOS granulosa cells in increasing its methylation status is unknown, which might be helpful in increasing the success rates in IVF patients of PCOS cases. Hypothesis: Altered polyamine metabolism might be related to increased homocysteine and SAM levels in normal and PCOS cases and affecting fertility; supplementation of polyamine/ SAM might improve the polyamine, SAM and homoscysteine scenario in the PCOS condition and improve the methylation status of affected genes and ovarian physiology in PCOS condition in PCOS like hyperandrogenized mice model and in human PCOS granulosa cells.