Steroid hormone biosynthesis - Homo sapiens (human)

Steroid hormones derived from cholesterol are a class of biologically active compounds in vertebrates. The cholesterol side-chain cleavage enzyme CYP11A1 catalyzes conversion of cholesterol, a C27 compound, to the first C21 steroid, pregnenolone, which is converted by a bifunctional enzyme complex to the gestagen hormone, progesterone [MD:M00107]. Pregnenolone and progesterone are the starting materials for the three groups of steroids: C21 steroids of glucocorticoids and mineralocorticoids, C19 steroids of androgens, and C18 steroids of estrogens. (i) Progesterone is converted by hydroxylations at carbons 21 and 11 to corticosterone, which is further modified by hydroxylation and oxydoreduction at carbon 18 to yield aldosterone, a mineralcorticoid [MD:M00108]. Cortisol, the main glucocorticoid, is formed from 17alpha-hydroxyprogesterone with 11-deoxycortisol as an intermediate [MD:M00109]. (ii) Male hormone testosterone is formed from pregnenolone by two pathways, delta5 pathway via dehydroepiandrosterone and delta4 pathway via androstenedione [MD:M00110]. The enzyme CYP17A1 is responsible for the 17,20 lyase and 17alpha-hydroxylase activities in respective pathways. (iii) Female hormones estrone and estradiol are formed from testosterone and 4-androstene-3,17-dione by oxidative removal of the C19 methyl group and subsequent aromatization of ring A [MD:M00111]. In addition to these three groups, recent studies show that there is another group, termed neurosteroids, synthesized in the brain rather than the peripheral endocrine gland.

Metabolism; Lipid metabolism

Homo sapiens (human) [GN:hsa]

PMID:10998348

Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K

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 351:67-77 (2000)

PMID:11469811

Tomlinson JW, Stewart PM

Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase.

Best Pract Res Clin Endocrinol Metab 15:61-78 (2001)

PMID:12604236

Higaki Y, Usami N, Shintani S, Ishikura S, El-Kabbani O, Hara A

Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone.

Chem Biol Interact 143-144:503-13 (2003)

PMID:12832414

Thomas JL, Duax WL, Addlagatta A, Brandt S, Fuller RR, Norris W

Structure/function relationships responsible for coenzyme specificity and the isomerase activity of human type 1 3 beta-hydroxysteroid dehydrogenase/isomerase.

J Biol Chem 278:35483-90 (2003)

PMID:15642792

Cavigelli SA, Monfort SL, Whitney TK, Mechref YS, Novotny M, McClintock MK

Frequent serial fecal corticoid measures from rats reflect circadian and ovarian  corticosterone rhythms.

J Endocrinol 184:153-63 (2005)

PMID:16413106

Holmes MC, Seckl JR

The role of 11beta-hydroxysteroid dehydrogenases in the brain.

Mol Cell Endocrinol 248:9-14 (2006)

PMID:16547389

Matsunaga T, Shintani S, Hara A

Multiplicity of mammalian reductases for xenobiotic carbonyl compounds.

Drug Metab Pharmacokinet 21:1-18 (2006)

PMID:17459698

Morris DJ, Latif SA, Hardy MP, Brem AS

Endogenous inhibitors (GALFs) of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2: derivatives of adrenally produced corticosterone and cortisol.

J Steroid Biochem Mol Biol 104:161-8 (2007)

PMID:17475203

Sanai M, Endo S, Matsunaga T, Ishikura S, Tajima K, El-Kabbani O, Hara A

Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol.

Arch Biochem Biophys 464:122-9 (2007)

PMID:17926129

Ghayee HK, Auchus RJ

Basic concepts and recent developments in human steroid hormone biosynthesis.

Rev Endocr Metab Disord 8:289-300 (2007)