A direct comparison of the transcriptional activities of progestins used in contraception and menopausal hormone therapy via the mineralocorticoid receptor.

A direct comparison of the transcriptional activities of progestins used in contraception and menopausal hormone therapy via the mineralocorticoid receptor. Biochem Biophys Res Commun. 2020 Mar 28;: Authors: Louw-du Toit R, Hapgood JP, Africander D Abstract A variety of structurally and functionally distinct progestins is used in contraception and menopausal hormone therapy (MHT). Some progestins elicit off-target effects by binding to steroid receptors other than the progesterone receptor, which may impact their therapeutic and side-effect profiles. We directly compared the binding affinities, efficacies and potencies of selected progestins via the mineralocorticoid receptor (MR). We did not detect a significant difference in the affinities of medroxyprogesterone acetate (MPA), norethisterone acetate (NET-A), levonorgestrel (LNG), gestodene (GES), etonogestrel (ETG), nestorone (NES) and nomegestrel acetate (NoMAC) for the MR, while these were significantly lower compared to drospirenone (DRSP). While GES and NoMAC display affinities indistinguishable from progesterone (P4), the binding affinity of DRSP is significantly greater and all other progestins significantly lower than that of P4. Dose-response analyses showed that P4, GES and ETG display indistinguishable MR antagonist potencies for transactivation to the well-known MR antagonist spironolactone, while LNG, NoMAC and DRSP are significantly more potent than spironolactone and ...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research