Regulatory effects of growth hormone, glucocorticoids, and thyroid hormone on the estrogen receptor level in the rat liver.
The multihormonal regulation of the estrogen receptor in the liver of female rats was studied under in vivo conditions. The steroid receptor level was assayed by hormone binding and specific mRNA analyzed by solution hybridization using a 35S-labeled RNA probe complementary to the ligand-binding domain of the estrogen receptor gene. Serum growth hormone levels were measured and correlated to the effects of glucocorticoid and thyroid hormone administration on the estrogen receptor expression. In animals subjected to adrenalectomy plus thyroidectomy, the estrogen receptor concentration was reduced from 59 fmol/mg cytosol protein to 10 fmol/mg protein (i.e., with 87% relative to control animals). Adrenalectomy or thyroidectomy alone caused a decrease with 14% and 66%, respectively. Substitution with 10 micrograms betamethasone and 1 microgram triiodothyronine daily for 9 days completely restored the receptor content to control levels. Substitution with either hormone alone increased, but only partially restored receptor levels. The effect of betamethasone alone was dose dependent from 10 micrograms/d to 100 micrograms/d. This dose dependence was not seen when the animal simultaneously received 1 microgram of triiodothyronine. Superphysiologic doses of triiodothyronine did not raise estrogen receptor levels above those seen in animals treated with physiologic doses. High doses of triiodothyronine (greater than 20 micrograms/d) decreased serum growth hormone levels. The estrogen receptor mRNA levels in livers from hypophysectomized animals were increased after treatment with growth hormone (2.5-fold), thyroid hormone (two-fold), and glucocorticoids (1.5-fold). The results obtained indicate a very complex regulation of liver estrogen receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Freyschuss
B
B
Department of Reproductive Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Sahlin
L
L
Eriksson
H A
HA
D000315:Adrenalectomy; D000818:Animals; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis* / Q000235:genetics; D013963:Thyroid Hormones / Q000494:pharmacology*; D013965:Thyroidectomy
D005938:Glucocorticoids; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013963:Thyroid Hormones; D013006:Growth Hormone