Low progesterone levels wen jing tang1/16/2024 In accordance, progesterone induces several hepatic cytochrome P450 enzymes, such as CYP3A4, especially during pregnancy when concentrations are much higher than usual. Progesterone and some of its metabolites, such as 5β-dihydroprogesterone, are agonists of the pregnane X receptor (PXR), albeit weakly so ( EC 50 >10 μM). Progesterone, through its neurosteroid active metabolites such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a positive allosteric modulator of the GABA A receptor. In addition, progesterone binds to and behaves as a partial agonist of the glucocorticoid receptor (GR), albeit with very low potency ( EC 50 >100-fold less relative to cortisol). Progesterone prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and glucocorticoids such as cortisol and corticosterone, and produces antimineralocorticoid effects, such as natriuresis, at physiological concentrations. Moreover, progesterone is also known to be an antagonist of the sigma σ 1 receptor, a negative allosteric modulator of nicotinic acetylcholine receptors, and a potent antagonist of the mineralocorticoid receptor (MR). It also functions as a ligand of the PGRMC1 (progesterone receptor membrane component 1) which impacts tumor progression, metabolic regulation, and viability control of nerve cells. In addition, progesterone is an agonist of the more recently discovered membrane progesterone receptors (mPRs), of which the expression has regulation effects in reproduction function ( oocyte maturation, labor, and sperm motility) and cancer although additional research is required to further define the roles. As a potent agonist of the nuclear progesterone receptor (nPR) (with an affinity of K D = 1 nM) the resulting effects on ribosomal transcription plays a major role in regulation of female reproduction. Progesterone is the most important progestogen in the body. See also: Pharmacodynamics of progesterone § Mechanism of action
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