title: 16α-hydroxyprogesterone: origin, biosynthesis and receptor interaction.
abstract: The metabolism of progesterone (PROG) by cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) results in the formation of both 17α-hydroxyprogesterone (17-OHPROG) and 16α-hydroxyprogesterone (16-OHPROG) in humans. Unlike 17-OHPROG, 16-OHPROG is not metabolised further in steroidogenic tissue. While this metabolite can be readily detected in serum and urine, its physiological role remains unclear. This paper reviews the production of 16-OHPROG by human CYP17A1 by providing insight into the catalysis of PROG by CYP17A1 and highlights the role of Ala105 in the 16α-hydroxylation reaction. As 16-OHPROG has been putatively linked to reproductive function, we investigated the interaction of this steroid metabolite with both isoforms of the human progesterone receptor (hPR). We show for the first time that 16-OHPROG can bind to both hPR-A and hPR-B and act as an agonist for both receptors.
authors.affiliation: Department of Biochemistry, University of Stellenbosch, Stellenbosch 7602, South Africa.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Storbeck
authors.forename: Pieter
authors.initials: P
authors.lastname: Swart
authors.forename: Donita
authors.initials: D
authors.lastname: Africander
authors.forename: Riaan
authors.initials: R
authors.lastname: Conradie
authors.forename: Renate
authors.initials: R
authors.lastname: Louw
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Swart
mesh_terms: D055162:Biocatalysis; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism
chemical_list: D006908:Hydroxyprogesterones; D011980:Receptors, Progesterone; C018975:16-hydroxyprogesterone; D013254:Steroid 17-alpha-Hydroxylase