MR effects on the peripheral stress response
In response to stressors, circuits converge on the brainstem to
stimulate sympathetic nervous system activation (Herman et al. ,
2016), and on the hypothalamic paraventricular nucleus to stimulate the
HPA axis (Lightman, Birnie and Conway-Campbell, 2020). MRs can stimulate
sympathetic outflow, as demonstrated by denervation studies in rat
models for hypertension (Rahmouni et al. , 2001). MRs also
crucially maintain the HPA axis set point, demonstrated by Mary
Dallman’s study that reinstated the hypothalamic and pituitary set point
in adrenalectomised rats with low dose corticosteroids (Dallman et
al. , 1989). In a more physiological setting, the MR antagonist RU28318
increased basal HPA axis activity and potentiated the initial rise in
ACTH and corticosterone secretion in response to stress (Ratka et
al. , 1989; van Haarst, Oitzl and de Kloet, 1997). In humans, systemic
treatment using MR antagonist spironolactone increased basal and stress
induced cortisol secretion (Cornelisse, Joels and Smeets, 2011). In
contrast, GR antagonism did not affect basal HPA axis activity but
instead attenuated the initial HPA stress response and prolonged
cortisol secretion by inhibiting GR negative feedback (Ratka et
al. , 1989; van Haarst, Oitzl and de Kloet, 1997).