In vivo and in vitro estimations of the direct effect of estrogen on rat hepatocytes tested by the changes in the unusual estrogen-binding protein content

• Published in: Journal of steroid biochemistry Vol. 35; no. 3; pp. 457 - 463
• Main Authors: Smirnova, O.V., Vishnyakova, T.G., Rozen, V.B., Shnyra, A.A., Bocharov, A.V., Spirov, V.G.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.03.1990
• Subjects: Animals; Carrier Proteins - analysis; Cells, Cultured; Estradiol - pharmacology; Growth Hormone - physiology; Liver - analysis; Liver - drug effects; Male; Rats; Rats, Inbred Strains; Receptors, Estrogen - analysis; Receptors, Estrogen - drug effects
• ISSN: 0022-4731
• DOI: 10.1016/0022-4731(90)90254-P

The direct effect of estradiol (E 2) on the hepatocytes of mature male rats has been examined by measuring the changes in the unusual estrogen-binding protein (UEBP) content and parallel measuring the level of liver estrogen receptors (ER). The content of UEBP ( N UEBP) and ER ( N ER) in the liver were determined using the quantitative methods for differential specific determination of the E 2-binding sites of these proteins. It has been shown that the administration of E 2 in vivo induced a considerable decrease in hepatic N UEBP not only in intact males, but also in hypophysectomized males during the initial period after the operation (when the content of hepatic ER was still high) and produced no effect in hypohysectomized males during the later period (when liver ER were depleted). Repeated administration of human growth hormone (hGH) (twice a day) resulted in a considerable increase in n er in hypophysectomized males and restored the sensitivity to the subsequent inhibitory effect of E 2 on UEBP. We also used rat hepatocytes after a 4-day primary culturing. These cells had a stable morpho-functional status, high ER level, and sex-differentiated UEBP content. Culturing of mature male rat hepatocytes in the medium containing E 2 at concentrations close to physiological levels (10 −10−10 −7) decreased N UEBP in a dose-dependent manner. Hexestrol (10 −7M) but not cholesterol (10 −5M) also exhibited a direct effect on N UEBP in cultured rat hepatocytes. The effect of E 2 was reversible: statistically significant increase in N UEBP was observed 3 days after 10 −9 M E; had been removed from the culturing medium. It was concluded that hepatocytes may be a primary target for E 2 under physiological conditions and that GH may modulate the direct effect of E 2 at the hepatic level by modifying the content of liver ER.