title: Exogenous steroids and the control of oestradiol secretion by human granulosa-lutein cells by follicle stimulating hormone and insulin-like growth factor-I.
abstract: This study first examined the relative activities of 17 alpha-hydroxylase, 17,20-lyase and aromatase in human granulosa-lutein cells by challenging the cells with steroid precursors in the oestradiol biosynthetic pathway. When cells from four patients were challenged with precursor steroids on the pathway to oestrogen synthesis (pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone and androstenedione at 5 x 10(-6) M), oestradiol (nmol/l) outputs after 1 day of culture were (median, interquartile range) as follows: 4.1 (2.1-8.8; pregnenolone), 3.1 (1.7-6.0; progesterone), 12.5 (6.9-18.1; 17 alpha-hydroxypregnenolone), 8.2 (4.1-16.7; 17 alpha-hydroxyprogesterone) and 251 (140-819; androstenedione). No further increases were seen when the steroid concentration was increased to 1 x 10(-5) M. Basal oestradiol secretion was 3.5 (1.6-8.2) nmol/l. We conclude that the conversion of pregnenolone/progesterone to oestradiol by granulosa-lutein cells is rate limited by 17 alpha-hydroxylase activity but that these cells are capable of oestradiol secretion (in the nmol/l range) in the absence of androstenedione. In the second part of this study we examined the control of granulosa-lutein oestradiol secretion by follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) in the presence and absence of exogenous androstenedione (10(-6) M). Cells were cultured for up to 6 days and basal oestradiol (nmol/l) fell dramatically over this period both in the presence and absence of androtenedione, e.g. from 339 (223-419) (median and interquartile range, cells from five patients cultured in the presence of androstenedion) after 2 days to 14 (7-59) after 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Manchester, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Wood
authors.forename: A
authors.initials: A
authors.lastname: Lambert
authors.forename: M A
authors.initials: MA
authors.lastname: Hooper
authors.forename: G G
authors.initials: GG
authors.lastname: Mitchell
authors.forename: W R
authors.initials: WR
authors.lastname: Robertson
mesh_terms: D000446:Aldehyde-Lyases / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*
chemical_list: D013256:Steroids; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases