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5α-Dihydroprogesterone

5α-Dihydroprogesterone (5α-DHP, allopregnanedione, or 5α-pregnane-3,20-dione) is an endogenous progestogen and neurosteroid that is synthesized from progesterone. It is also an intermediate in the synthesis of allopregnanolone and isopregnanolone from progesterone.

5α-DHP is metabolized by the aldo-keto reductases (AKRs) AKR1C1, AKR1C2, and AKR1C4 with high catalytic efficiency. AKR1C1 preferentially forms 20α-hydroxy-5α-pregnane-3-one while AKR1C2 preferentially forms allopregnanolone. Similarly AKR1C1 reduces and consequently inactivates allopregnanolone into 5α-pregnane-3α,20α-diol. In contrast to the other AKRs, AKR1C3 has low catalytic efficiency for reduction of 5α-DHP. These AKRs are highly expressed in the human liver and mammary gland but have relatively modest expression in the human brain and uterus.

5α-DHP is an agonist of the progesterone receptor and a positive allosteric modulator of the GABAA receptor (albeit with an affinity for this receptor that is regarded as relatively low (in comparison to 3α-hydroxylated progesterone metabolites such as allopregnanolone and pregnanolone)). It has also been found to act as a negative allosteric modulator of the GABAA-rho receptor. The steroid has been found to possess 82% of the affinity of progesterone for the progesterone receptor in rhesus monkey uterus. 5α-Dihydroprogesterone has been said to possess about 33% of the relative progestogenic potency of progesterone. In addition, it is a weak agonist of the pregnane X receptor (PXR) (EC50 10,000 μM), with approximately six-fold lower potency relative to its 5β-isomer, 5β-dihydroprogesterone.

Allopregnanolone is transformed back into 5α-DHP by 3α-hydroxysteroid oxidoreductase, and conversion of allopregnanolone into 5α-DHP is responsible for the progestogenic activity of allopregnanolone. 5α-DHP, via the progesterone receptor, and allopregnanolone, via the GABAA receptor, act together to induce lordosis in animals. A study found that 41% of allopregnanolone that was administered via injection was transformed into 5α-DHP in the rat brain.

Levels of 5α-DHP have been quantified.

Chemistry

References

References

  1. (2007). "Handbook of Contemporary Neuropharmacology".
  2. (October 2007). "Neurosteroid regulation of central nervous system development". Pharmacol. Ther..
  3. (November 2001). "The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders". Brain Res. Brain Res. Rev..
  4. (January 2014). "Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism". Steroids.
  5. (October 2000). "Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones". Biochem. J..
  6. (September 1993). "Progesterone receptor-mediated effects of neuroactive steroids". Neuron.
  7. (2008). "Antinociceptive profile of ring A-reduced progesterone metabolites in the formalin test". Pain.
  8. (2002). "Medicinal chemistry and molecular pharmacology of GABA(C) receptors". Curr Top Med Chem.
  9. (February 1977). "A specific progesterone receptor of myometrial cytosol from the rhesus monkey". J. Steroid Biochem..
  10. (22 May 2000). "Menopause: Biology and Pathobiology". Academic Press.
  11. (1998). "The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions". J. Clin. Invest..
  12. (February 1999). "Indomethacin inhibits lordosis induced by ring A-reduced progestins: possible role of 3alpha-oxoreduction in progestin-facilitated lordosis". Horm Behav.
  13. (November 1995). "Ring A reduced progestins potently stimulate estrous behavior in rats: paradoxical effect through the progesterone receptor". Physiol. Behav..
  14. (September 2015). "Reproducibility of an assay to measure serum progesterone metabolites that may be related to breast cancer risk using liquid chromatography-tandem mass spectrometry". Horm Mol Biol Clin Investig.
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neurosteroids progestogens gabaa-receptor-positive-allosteric-modulators gabaa-rho-receptor-negative-allosteric-modulators pregnane-x-receptor-agonists diketones pregnanes 5α-pregnanes
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