  The progesterone receptor (PR) mediates progesterone regulation of female
reproductive physiology, as well as gene transcription in non-reproductive
tissues, such as brain, bone, lung and vasculature, in both women and men. An
unusual property of progesterone is its high affinity for the mineralocorticoid
receptor (MR), which regulates electrolyte transport in the kidney in humans
and other terrestrial vertebrates. In humans, rats, alligators and frogs,
progesterone antagonizes activation of the MR by aldosterone, the physiological
mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark,
ray-finned fishes and chickens, progesterone activates the MR. Interestingly,
cartilaginous fishes and ray-finned fishes do not synthesize aldosterone,
raising the question of which steroid(s) activate the MR in cartilaginous
fishes and ray-finned fishes. The simpler synthesis of progesterone, compared
to cortisol and other corticosteroids, makes progesterone a candidate
physiological activator of the MR in elephant sharks and ray-finned fishes.
Elephant shark and ray-finned fish MRs are expressed in diverse tissues,
including heart, brain and lung, as well as, ovary and testis, two reproductive
tissues that are targets for progesterone, which together suggests a
multi-faceted physiological role for progesterone activation of the MR in
elephant shark and ray-finned fish. The functional consequences of progesterone
as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish
and chicken MRs are not fully understood. Indeed, little is known of
physiological activities of progesterone via any vertebrate MR.
