Biomaterial Database

Enzyme interactions of 2,10-ethanoandrostene-3,17-dione: aromatase and 17 beta-hydroxysteroid dehydrogenase. 1990

A T Greway, and M Mentzer, and M A Levy

Department of Medicinal Chemistry, Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.

An analogue of androstenedione containing an ethano bridge between carbons 2 and 10 of the A ring of the steroid, 1, has been evaluated as an inhibitor and a possible substrate of human placental aromatase. This compound was found to be a competitive inhibitor versus androstenedione (Kis = 25 +/- 2 nM) of the aromatase activity. Analyses of the incubation mixtures of 1 with human placental microsomes and NADPH by GC-MS indicated the formation of a new compound having an increase in molecular weight of 2 mass units (300 m.u.) from that of the parent steroid (298 m.u.). Subsequent analyses of incubations of 1 with an isolated 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) from Pseudomonas testosteronii in the presence of NADPH resulted in the formation of a new compound having the same retention time and molecular mass as that found for the product from the placental microsome incubation. Consequently, steroid 1 is both an inhibitor of human placental aromatase and a substrate for 17 beta-HSD.

UI	MeSH Term	Description	Entries
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D010920	Placenta	A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).	Placentoma, Normal,Placentome,Placentas,Placentomes
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000735	Androstenedione	A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.	4-Androstene-3,17-dione,delta-4-Androstenedione,4 Androstene 3,17 dione,delta 4 Androstenedione
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D015067	17-Hydroxysteroid Dehydrogenases	A class of enzymes that catalyzes the oxidation of 17-hydroxysteroids to 17-ketosteroids. EC 1.1.-.	17 beta-Hydroxysteroid Dehydrogenases,Testosterone Dehydrogenases,17-Ketosteroid Reductases,17 Hydroxysteroid Dehydrogenases,17 Ketosteroid Reductases,17 beta Hydroxysteroid Dehydrogenases,Dehydrogenases, 17 beta-Hydroxysteroid,Dehydrogenases, 17-Hydroxysteroid,Dehydrogenases, Testosterone,Reductases, 17-Ketosteroid
D047072	Aromatase Inhibitors	Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.	Aromatase Inhibitor,Inhibitor, Aromatase,Inhibitors, Aromatase
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In