Ethinylestradiol interacts with liver microsomes and induces binding sites for steroid hormones in the male rat liver.
The present work focuses on the interaction of 17 alpha-ethinyl estrogen derivatives with the [3H]dexamethasone ([3H]DEX) binding site from male rat liver microsomes and the induction of this site by the in vivo administration of natural and synthetic estrogens. [3H]DEX binds to a single-saturating binding site (Kd = 100 nM; maximal binding = 13 pmol/mg of protein) in the liver microsomes. In competition experiments, ethinylestradiol (EE2) and mestranol were able to inhibit [3H]DEX binding to microsomes, whereas natural estrogens, tamoxifen or estrogen sulfates were ineffective. Saturation analysis performed by incubating [3H]EE2 with liver microsomes revealed the existence of a low-affinity (Kd = 280 +/- 30 nM) and high capacity (maximal binding = 16 +/- 2 pmol/mg of protein) binding site. Saturation, competition and dissociation experiments suggest that [3H]DEX and [3H]EE2 interact with the same microsomal entity. Synthetic and natural estrogens increased the hepatic expression of the [3H]DEX binding site in immature, hypothyroid and hypophysectomized male rats. This induction required at least 2 days of treatment, and could only be achieved by pharmacological doses of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)
Fernández
L
L
Departamentos de Endocrinología Celular y Molecular, Universidad de Las Palmas de Gran Canaria, Canary Islands, Spain.
Boada
L D
LD
Luzardo
O P
OP
Zumbado
M
M
Díaz-Chico
J C
JC
Díaz-Chico
B N
BN
Chirino
R
R
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D003907:Dexamethasone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D007016:Hypophysectomy; D007037:Hypothyroidism / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004967:Estrogens; D004997:Ethinyl Estradiol; D003907:Dexamethasone