17α-Hydroxypregnenolone explained

17α-Hydroxypregnenolone is a pregnane (C21) steroid that is obtained by hydroxylation of pregnenolone at the C17α position. This step is performed by the mitochondrial cytochrome P450 enzyme 17α-hydroxylase (CYP17A1) that is present in the adrenal and gonads. Peak levels are reached in humans at the end of puberty and then decline.[1] High levels are also achieved during pregnancy. It is also a known neuromodulator.

Prohormone

17α-Hydroxypregnenolone is considered a prohormone in the formation of dehydroepiandrosterone (DHEA), itself a prohormone of the sex steroids.

This conversion is mediated by the enzyme 17,20 lyase. As such 17α-hydroxypregenolone represents an intermediary in the Δ5 pathway that leads from pregnenolone to DHEA. 17α-Hydroxypregneolone is also converted to 17α-hydroxyprogesterone, a prohormone for glucocorticosteroids and androstenedione through the activity of 3α-hydroxysteroid dehydrogenase.

Clinical use

Measurements of 17α-hydroxypregnenolone are useful in the diagnosis of certain forms of congenital adrenal hyperplasia.[2] In patients with congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency 17α-hydroxypregnenolone is increased, while in patients with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency levels are low to absent.

Neurosteroid

17α-hydroxypregnenolone is a known neuromodulator as its acts in the central nervous system. Specifically, it is known to modulate locomotion.[3]

See also

Notes and References

  1. Hill M, Lukác D, Lapcík O, Sulcová J, Hampl R, Pouzar V, Stárka L . Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects . Clinical Chemistry and Laboratory Medicine . 37 . 4 . 439–47 . April 1999 . 10369116 . 10.1515/CCLM.1999.072 . 41315909 .
  2. Riepe FG, Mahler P, Sippell WG, Partsch CJ . Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period . The Journal of Clinical Endocrinology and Metabolism . 87 . 9 . 4301–6 . September 2002 . 12213889 . 10.1210/jc.2002-020452 . free .
  3. Tsutsui K, Haraguchi S, Vaudry H . 7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates . General and Comparative Endocrinology . 265 . 97–105 . September 2018 . 28919448 . 10.1016/j.ygcen.2017.09.014 . 5636071 .