Considerations
Pharmacological MR manipulation comes with some considerations.
Fludrocortisone binds to some extent to the GR (Agarwal, Coupry and
Philippe, 1977; Grossmann et al. , 2004). Furthermore,
fludrocortisone administration reduces cortisol release (Nowacki,
Wingenfeld, Kaczmarczyk, Chae, Abu-Tir, et al. , 2020),
highlighting MR function in HPA axis feedback regulation, but
complicating interpretation, given potential consequences for GR.
Fludrocortisone also activates aldosterone-selective MR in the NTS,
although, no effects were found on blood pressure (Otte, Wingenfeld,
Kuehl, Richter, et al. , 2015; Wingenfeld et al. , 2015) or
aldosterone release (Nowacki, Wingenfeld, Kaczmarczyk, Chae, Salchow,et al. , 2020). Spironolactone is known to have effects on PR and
progesterone acts as an MR antagonist (Quinkler and Diederich, 2002;
Struthers, Krum and Williams, 2008). Therefore, sex specific effects on
MR function and cognition must be considered in future studies. Although
some studies report none (Piber et al. , 2016; Deuter et
al. , 2017), the consequence of genetic MR haplotypes did depend on sex
(M D Klok et al. , 2011; Wirz et al. , 2017). Notably, age
related differences were reported in fludrocortisone effects in major
depressive disorder (MDD) patients (see below (Otte, Wingenfeld, Kuehl,
Kaczmarczyk, et al. , 2015; Otte, Wingenfeld, Kuehl, Richter,et al. , 2015)) compared to controls (Hinkelmann et al. ,
2015).
Overall, increasing evidence strongly suggest MR function as essential
for cognitive and emotional function. These MR mediated effects seem to
be moderated by age, sex, and potentially other variables. Thus, further
research into MR effects is not only warranted in healthy humans but
also in patients with stress-related mental disorders who often show
alterations in cognitive and emotional function.