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Exogenous steroids and the control of oestradiol secretion by human granulosa-lutein cells by follicle stimulating hormone and insulin-like growth factor-I. 1994

A M Wood, and A Lambert, and M A Hooper, and G G Mitchell, and W R Robertson
Department of Medicine, University of Manchester, UK.

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)

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008184 Luteal Cells PROGESTERONE-producing cells in the CORPUS LUTEUM. The large luteal cells derive from the GRANULOSA CELLS. The small luteal cells derive from the THECA CELLS. Lutein Cells,Granulosa-Luteal Cells,Granulosa-Lutein Cells,Large Luteal Cells,Small Luteal Cells,Theca-Luteal cells,Theca-Lutein Cells,Cell, Granulosa-Luteal,Cell, Granulosa-Lutein,Cell, Large Luteal,Cell, Luteal,Cell, Lutein,Cell, Small Luteal,Cell, Theca-Lutein,Cells, Granulosa-Luteal,Cells, Granulosa-Lutein,Cells, Large Luteal,Cells, Luteal,Cells, Lutein,Cells, Small Luteal,Cells, Theca-Lutein,Granulosa Luteal Cells,Granulosa Lutein Cells,Granulosa-Luteal Cell,Granulosa-Lutein Cell,Large Luteal Cell,Luteal Cell,Luteal Cell, Large,Luteal Cell, Small,Luteal Cells, Large,Luteal Cells, Small,Lutein Cell,Small Luteal Cell,Theca Luteal cells,Theca Lutein Cells,Theca-Luteal cell,Theca-Lutein Cell,cell, Theca-Luteal,cells, Theca-Luteal
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D005260 Female Females
D005640 Follicle Stimulating Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D006107 Granulosa Cells Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH). Cell, Granulosa,Cells, Granulosa,Granulosa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000446 Aldehyde-Lyases Enzymes that catalyze a reverse aldol condensation. A molecule containing a hydroxyl group and a carbonyl group is cleaved at a C-C bond to produce two smaller molecules (ALDEHYDES or KETONES). EC 4.1.2. Aldolases,Aldehyde Lyases

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