Synthesis of deuterium- and tritium-labelled 4-hydroxyandrostene-3,17-dione, an aromatase inhibitor, and its metabolism in vitro and in vivo in the rat

Biochemical Pharmacology
D A MarshA M Brodie


The metabolism of the aromatase inhibitor-4-hydroxyandrostenedione (4-OHA) was studied in vitro and in vivo in the rat. To accomplish this, deuterium- and tritium-labeled 4-OHA were prepared from 4-hydroxyandrosta-4, 6-dione-3,17-dione. The latter was synthesized from 4-androstene-3,17-dione. Using deuterated 4-OHA in in vitro incubations of rat ovarian microsomes, 4-hydroxytesterone (4-OHT) was identified by gas chromatography/mass spectroscopy as the major metabolite. 4-OHT constituted approximately 20% of the total radioactivity from [6,7-3H]-4-OHA in the ovarian microsomal incubations. Conversion of [6,7-3H]-4-OHA to 4-hydroxyesterone was approximately 0.1%. The major metabolite of [6, 7-3H]-4-OHA in vivo identified in the free, neutral fraction of rat blood was 3 beta-hydroxyandrostane-4,17-dione. The metabolite accounted for approximately 5% of the total radio-activity in the blood, Whereas 4-OHT accounted for only 0.1%, 4-OHT inhibited in vitro ovarian aromatization by 59%, but 3 beta-hydroxyandrostane-4-17-dione had little effect. It was concluded that the in vivo effects of 4-OHA previously reported are largely due to its own activity although additional effects of its metabolic products cannot be excluded.


Feb 1, 1986·Journal of Steroid Biochemistry·A B FosterI B Parr
Mar 1, 1990·Journal of Steroid Biochemistry·J KhubiehJ Chakraborty
Jan 1, 1988·Pharmacology & Therapeutics·S P Robinson, V C Jordan
Jan 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·J L Zhou, A M Brodie
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·A M BrodieB Long
Jul 1, 1986·Journal of Clinical Pharmacology·T A Baillie, A W Rettenmeier
Mar 1, 1988·Journal of Chemical Ecology·F X Webster, G D Prestwich

Related Concepts

Aromatase Inhibitors
Rats, Laboratory
In Vitro [Publication Type]

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Lipidomics & Rhinovirus Infection

Lipidomics can be used to examine the lipid species involved with pathogenic conditions, such as viral associated inflammation. Discovered the latest research on Lipidomics & Rhinovirus Infection.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Torsion Dystonia

Torsion dystonia is a movement disorder characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Here is the latest research.

Generating Insulin-Secreting Cells

Reprogramming cells or using induced pluripotent stem cells to generate insulin-secreting cells has significant therapeutic implications for diabetics. Here is the latest research on generation of insulin-secreting cells.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Epigenome Editing

Epigenome editing is the directed modification of epigenetic marks on chromatin at specified loci. This tool has many applications in research as well as in the clinic. Find the latest research on epigenome editing here.