In vitro metabolism of gestodene in target organs: formation of A-ring reduced derivatives with oestrogenic activity

European Journal of Pharmacology
A E LemusG Pérez-Palacios

Abstract

Gestodene (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4,5-gonadien-3-one), the most potent progestin ever synthesized, stimulates breast cancer cell growth through an oestrogen receptor-mediated mechanism, and its use in hormonal contraception has been associated with side effects attributable to oestrogenic actions. These observations have remained controversial, since gestodene does not bind to the oestrogen receptor or exert oestrogen-like activities. Recently, we have demonstrated that non-phenolic gestodene derivatives interact with oestrogen receptors and induce oestrogenic effects in cell expression systems. To assess whether gestodene is biotransformed to metabolites with intrinsic oestrogenic potency, [3H]- and [14C]-labelled gestodene were incubated in vitro with rat anterior pituitary, hypothalamus and ventral prostate homogenates under different experimental conditions. The most remarkable finding was the isolation and identification of 3beta,5alpha-tetrahydrogestodene and 3alpha,5alpha-tetrahydrogestodene as metabolic conversion products of gestodene, presumably with 5alpha-dihydrogestodene as intermediate. The overall results seem to indicate that the weak oestrogenic effects attributable to gestodene could be me...Continue Reading

References

Mar 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·A E LemusG Pérez-Palacios
Jun 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·B van der BurgS W de Laat
Nov 1, 1990·Pharmacology, Biochemistry, and Behavior·G MoralíG Pérez-Palacios
Jan 1, 1985·Journal of Steroid Biochemistry·B A ChávezG Pérez-Palacios
Jun 1, 1994·Molecular and Cellular Endocrinology·E KalkhovenB van der Burg
Jan 1, 1994·Annual Review of Biochemistry·D W Russell, J D Wilson
Dec 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·W G SchoonenH J Kloosterboer
Aug 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·S Ward, D J Back
Jan 1, 1997·Brain Research Bulletin·F CelottiA Poletti

❮ Previous
Next ❯

Citations

Dec 16, 2003·The Journal of Steroid Biochemistry and Molecular Biology·J Shields-BotellaJ Paris
Sep 6, 2002·Pharmacology, Biochemistry, and Behavior·G MoralíG Pérez-Palacios
Feb 19, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Rocio García-BecerraFernando Larrea
Feb 22, 2011·Steroids·Alfred O Mueck, Regine Sitruk-Ware
Mar 8, 2005·The Journal of Steroid Biochemistry and Molecular Biology·J Shields-BotellaJ R Pasqualini
Dec 15, 2020·Pharmacology & Therapeutics·Alexis J BickJanet P Hapgood
Jul 21, 2004·The Journal of Steroid Biochemistry and Molecular Biology·Rocio García-BecerraFernando Larrea

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

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.

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.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.