Metabolism of 5α-dihydroprogesterone in women and men: 3β- and 3α- ,6α-dihydroxy-5α-pregnan-20-ones are major urinary metabolites

Journal of Clinical Endocrinology and Metabolism

Volumn 81, Issue 10, 1996, Pages 3644-3649

  Chantilis, Sam ^a   Dombroski, Raymond ^a   Shackleton, Cedric H L ^b   Casey, M Linette ^a   Macdonald, Paul C ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b CHILDREN S HOSPITAL OAKLAND RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5ALPHA PREGNANE 3,20 DIONE; DRUG METABOLITE; TRACER;

ADULT; ARTICLE; BOLUS INJECTION; CANCER CELL CULTURE; COLUMN CHROMATOGRAPHY; FEMALE; GAS CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; HYDROXYLATION; INTRAVENOUS DRUG ADMINISTRATION; ISOTOPE LABELING; MALE; MASS SPECTROMETRY; NORMAL HUMAN; PRIORITY JOURNAL; PROGESTERONE METABOLISM; RADIOACTIVITY; THIN LAYER CHROMATOGRAPHY; URINALYSIS; URINARY EXCRETION;

5-ALPHA-DIHYDROPROGESTERONE; ADOLESCENT; ADULT; CARBON RADIOISOTOPES; FEMALE; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HUMANS; HYDROXYLATION; LIVER; MALE; MIDDLE AGED; PREGNANEDIONES; PREGNANOLONE; PROGESTERONE; TRITIUM;

MAMMALIA;

EID: 0029842528     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.81.10.3644     Document Type: Article

References (31)

1. MacDonald PC, Dombroski RA, Casey ML. 1991 Recurrent secretion of progesterone in large amounts: an endocrine J metabolic disorder unique to young women? Endocr Rev. 12:372-401.
2. Dombroski RA, Casey ML, MacDonald PC. 1993 The metabolic disposition of plasma 5α-dihydroprogesterone (5α-pregnane-3, 20-dione) in women and men. J Clin Endocrinol Metab. 77:944-948.
3. Tait JF, Tait SA. 1991 The effect of plasma protein binding on the metabolism of steroid hormones. J Endocrinol. 131:339-357.
4. Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM. 1986 Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 232:1004-1007.
5. Purdy RH, Morrow AL, Blinn JR, Paul SM. 1990 Synthesis, metabolism, pharmacological activity of 3α-hydroxysteroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes. J Med Chem. 33:1572-1581.
6. Gyermek L, Iriate J, Crabbé P. 1968 Steroids. CCCX. Structure-activity relationship of some steroidal hypnotic agents. J Med Chem. 11:117.
7. Phillips GH. 1975 Structure-activity relationships in steroidal anaesthetics. J Steroid Biochem. 6:607-613.
8. Carl P, Hogskilde S, Nielsen JW, et al. 1990 Pregnanolone emulsion. A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent. Anaesthesia. 45:189-197.
9. Oliver AE, Deamer DW, Akeson M. 1991 Evidence that sensitivity to steroid anesthetics appears late in evolution. Brain Res. 557:298-302.
10. Casey ML, MacDonald PC. 1982 Extraadrenal formation of a mineralocorticosteroid: deoxycorticosterone and deoxycorticosterone sulfate biosynthesis and metabolism. Endocr Rev. 3:396-403.
11. Weir RJ, Goig A, Fraser R, et al. 1976 Studies of the renin-angiotensin-aldosterone system, cortisol, DOC, and ADH in pregnancy. In: Lindheimer MD, Katz AL, Zuspan FP. eds. Hypertension in pregnancy. New York: Wiley and Sons; 251-261.
12. Parker CR, Rush AJ, MacDonald PC. 1983 Serum concentrations of deoxycorticosterone in women during the luteal phase of the ovarian cycle are not suppressed by dexamethasone treatment. J Steroid Biochem. 19:1313-1317.
13. Winkel CA, Parker CR, Simpson ER, MacDonald PC. 1980 Production rate of deoxycorticosterone in women during the follicular and luteal phases of the ovarian cycle: the role of extraadrenal 21-hydroxylation of circulating progesterone in deoxycorticosterone production. J Clin Endocrinol Metab. 51:1354-1358.
14. Parker CR, Winkel CA, Rush AJ, Porter JC, MacDonald PC. 1981 Plasma concentrations of 11-deoxycorticosterone in women during the menstrual cycle. Obstet Gynecol. 58:26-30.
15. Siiteri PK. 1963 The isolation of urinary estrogens and determination of their specific activities following the administration of radioactive precursors to humans. Steroids. 2:687-712.
16. Shackleton CHL. 1986 Profiling steroid hormones and urinary steroids. J Chromatogr. 379:91-156.
17. Isaacs JT, McDermott IR, Coffey DS. 1979 Characterization of two new enzymatic activities of the rat ventral prostate: 5α-androstane-3β,17β-diol 6α-hydroxylase and 5α-androstane-3β,17β-diol 7α-hydroxylase. Steroids. 33: 675-692.
18. Desgres J, Fay L, Jo D, Guiguet M, Padieu P. 1984 Oxidoreductive and hydroxylating metabolism of progesterone in rat liver epithelial cell lines. J Steroid Biochem. 21:391-403.
19. CO human breast cancer cells. II. Intracellular metabolic path of progesterone and synthetic progestins. J Steroid Biochem. 25:911-916.
20. Strömstedt M, Warner M, Banner CD, MacDonald PC, Gustafsson J-A. 1993 Role of brain P450 in regulation of the level of anaesthetic steroids in the brain. Mol Pharmacol. 44:1077-1083.
21. Haaparanta T, Glaumann H, Gustafsson J-A. 1984 Characterization and endocrine regulation of the cytochrome P-450 dependent microsomal hydroxylation of 5α-androstane-3β 17β-diol in the rat ventral prostate. Endocrinology. 114:2293-2300.
22. Gemzik B, Jacob S, Jennings S, Veltman J, Parkinson A. 1992 Species differences in 5α-androstane-3β,17β-diol hydroxylation by rat, monkey, and human prostate microsomes. Arch Biochem Biophys. 296:374-383.
23. Sundin M, Warner M, Haaparanta T, Gustafsson J-A. 1987 Isolation of catalytic activity of cytochrome P-450 from ventral prostate of control rats. J Biol Chem. 262:12293-12297.
24. Ofner P, Vena RL. 1974 Acetylation and hydroxylation of 5α-androstane-3β,17β-diol by prostate and epididymis. Steroids. 24:261-277.
25. Morfin RF, Di Stefano S, Charles J-F, Floch HH. 1977 Precursors for 6β- and 7α-hydroxylations of 5α-androstane-3β,17β-diol by human normal and hyperplastic prostates. Biochimie. 59:637-644.
26. 3 steroid metabolite in the rat ventral prostate: 5α-androstane-3β,6α,17β-triol. Steroids. 33:639-657.
27. Gemzik B, Parkinson A. 1992 Hydroxylation of 5α-androstane-3β,17β-diol by rat prostate microsomes: potent inhibition by imidazole-type antimycotic drugs and lack of inhibition by steroid 5α-reductase inhibitors. Arch Biochem Biophys. 296:366-373.
28. Gemzik B, Green J, Parkinson A. 1992 Hydroxylation of 5α-androstane-3β,17β-diol by rat prostate microsomes: effects of antibodies and chemical inhibitors of cytochrome P450 enzymes. Arch Biochem Biophys. 296:355-365.
29. Warner M, Strömstedt M, Möller L, Gustafsson J-A. 1989 Distribution and regulation of 5α-androstane-3β,17β-diol hydroxylase in the rat central nervous system. Endocrinology. 124:2699-2705.
30. O'Hare MJ, Nice EC, McIlhinney RAJ, Capp M. 1981 Progesterone synthesis, secretion and metabolism by human teratoma-derived cell-lines. Steroids. 38:719-737.
31. Fennessey PV, Pike AW, Gonzales-Aller C, Horwitz KB. 1986 Progesterone metabolism in T47Dco human breast cancer cells. I. 5α-Pregnane-3β:6α-diol-20-one is the secreted product. J Steroid Biochem. 25:641-648.