Effect of a diphenylethylenediamine platinum complex on steroidogenesis in rats. 1996

T F Sergejew, and R W Hartmann
Fachrichtung 12.1 Pharmazeutische Chemie, Universität des Saarlandes, Saarbrücken, Germany.

Although less cytotoxic, the new platinum complex [meso-1,2-bis(2,6-difluoro-4-hydroxyphenyl)-ethylenediamine]sulfatopl atinum (II) (2) is equipotent to cisplatin (1) in the oestrogen-dependent MXT mammary tumour of the mouse. As this may be due to oestrogen level-lowering properties, we compared the effect of 1 and 2 on steroidogenesis in the rat. A single dose of 1 and 2 (20 mumol/kg s.c.) decreased plasma testosterone level in male rats by 90% (1, day 3) and 80% (2, day 7). Luteinizing hormone level remained unchanged in intact and in ovariectomized rats. The activities of the following testicular enzymes were decreased (day 7): cholesterol side-chain cleavage enzyme (1: 33%; 2: 36%), 3 beta-hydroxysteroid dehydrogenase/delta 4,delta 5-isomerase (1: 31%; 2: 48%) and 17 alpha-hydroxylase/17,20-lyase (1: 21%; 2: 15%). Testicular microsomal cytochrome P450 content was also diminished (1: 60%; 2: 49%, day 7). Corticosterone level in plasma and biosynthesis in adrenal explants was not affected, indicating the selectivity of action at the gonadal level. In vitro, neither 1 nor 2 (2 and 20 microM) influenced binding of human chorionic gonadotropin to testis interstitial cells during an observation period up to 21 h. These results suggest that 1 and 2 act at the gonadal level by inhibiting the expression of the steroidogenic enzymes. They do not, however, inactivate the luteinizing hormone receptor.

UI MeSH Term Description Entries
D007986 Luteinizing Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE 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. ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D008297 Male Males
D009944 Organoplatinum Compounds Organic compounds which contain platinum as an integral part of the molecule. Compounds, Organoplatinum
D010052 Ovariectomy The surgical removal of one or both ovaries. Castration, Female,Oophorectomy,Bilateral Ovariectomy,Bilateral Ovariectomies,Castrations, Female,Female Castration,Female Castrations,Oophorectomies,Ovariectomies,Ovariectomies, Bilateral,Ovariectomy, Bilateral
D010984 Platinum A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". Platinum Black
D011388 Prolactin A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate. Lactogenic Hormone, Pituitary,Mammotropic Hormone, Pituitary,Mammotropin,PRL (Prolactin),Hormone, Pituitary Lactogenic,Hormone, Pituitary Mammotropic,Pituitary Lactogenic Hormone,Pituitary Mammotropic Hormone
D011974 Receptors, LH Those protein complexes or molecular sites on the surfaces and cytoplasm of gonadal cells that bind luteinizing or chorionic gonadotropic hormones and thereby cause the gonadal cells to synthesize and secrete sex steroids. The hormone-receptor complex is internalized from the plasma membrane and initiates steroid synthesis. Chorionic Gonadotropin Receptors,Human Chorionic Gonadotropin Receptors,ICSH Receptors,LH Receptors,LH-hCG Receptor,LH-hCG Receptors,Luteinizing Hormone Receptors,Lutropin Receptor,Lutropin Receptors,Receptors, Chorionic Gonadotropin,Receptors, Human Chorionic Gonadotropin,Receptors, Interstitial Cell-Stimulating Hormone,Receptors, Luteinizing Hormone,hCG Receptors,Chorionic Gonadotropin Receptor,Human Chorionic Gonadotropin Receptor,LH Receptor,Luteinizing Hormone Receptor,Receptors, ICSH,Receptors, Interstitial Cell Stimulating Hormone,Receptors, LH-hCG,Receptors, Lutropin,Receptors, hCG,hCG Receptor,Gonadotropin Receptor, Chorionic,Gonadotropin Receptors, Chorionic,Hormone Receptor, Luteinizing,Hormone Receptors, Luteinizing,LH hCG Receptor,LH hCG Receptors,Receptor, Chorionic Gonadotropin,Receptor, LH,Receptor, LH-hCG,Receptor, Luteinizing Hormone,Receptor, Lutropin,Receptor, hCG,Receptors, LH hCG
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D003345 Corticosterone An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
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

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