Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives

Journal Article · Thu Sep 01 04:00:00 EDT 1988 · Contraception; (United States)

DOI:https://doi.org/10.1016/0010-7824(88)90104-7· OSTI ID:6561676

Kloosterboer, H J; Vonk-Noordegraaf, C A; Turpijn, E W

The relative binding affinities (RBAs) of four progestational compounds (norethisterone, levonorgestrel, 3-keto-desogestrel and gestodene) for the human progesterone and androgen receptors were measured in MCF-7 cytosol and intact MCF-7 cells. For the binding to the progesterone receptor, both Org 2058 and Org 3236 (or 3-keto-desogestrel) were used as labelled ligands. The following ranking (low to high) for the RBA of the nuclear (intact cells) progesterone receptor irrespective of the ligand used is found: norethisterone much less than levonorgestrel less than 3-keto-destogestrel less than gestodene. The difference between the various progestagens is significant with the exception of that between 3-keto-desogestrel and gestodene, when Org 2058 is used as ligand. For the cytosolic progesterone receptor, the same order is found with the exception that similar RBAs are found for gestodene and 3-keto-desogestrel. The four progestagens clearly differ with respect to binding to the androgen receptor using dihydrotestosterone as labelled ligand in intact cells; the ranking (low to high) is: norethisterone less than 3 keto-desogestrel less than levonorgestrel and gestodene. The difference between 3-keto-desogestrel and levonorgestrel or gestodene is significant. The selectivity indices (ratio of the mean RBA for the progesterone receptor to that of androgen receptor) in intact cells are significantly higher for 3-keto-desogestrel and gestodene than for levonorgestrel and norethisterone. From these results we conclude that the introduction of the 18-methyl in norethisterone (levonorgestel) increases both the binding to the progesterone and androgen receptors.

• Research Organization: Organon Scientific Development Group, Oss (Netherlands)
• OSTI ID: 6561676
• Journal Information: Contraception; (United States), Journal Name: Contraception; (United States) Vol. 38:3; ISSN CCPTA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANDROGENS
ANDROSTANES
BIOCHEMICAL REACTION KINETICS
HORMONES
IN VITRO
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
LIGANDS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PREGNANES
PROGESTERONE
PROTEINS
REACTION KINETICS
RECEPTORS
STEROID HORMONES
STEROIDS
TRACER TECHNIQUES
TRITIUM COMPOUNDS