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The possibility of direct androgen determination of high unusual estrogen-binding protein (UEBP) level in female rat hepatocytes to the level typical to the males was studied. The direct effect of androgen (A) on the UEBP content in hepatocytes of ovariectomized female rats was shown by estimation in vivo and on hepatocyte culture. It has been revealed that the permissive action of growth hormone (GH) is necessary for normal expression of direct androgen effect. The latter has been stable after cessation of hormone action. High concentration of GH was found to possess positive regulatory effect on the UEBP in hepatocytes of ovariectomized rats. Effect of GH quickly disappeared after hormone withdrawal and was under negative regulation by physiological concentrations of A. It was concluded that A owing to its direct action together with permissive influence of GH is capable of determining stable expression of male phenotype of the UEBP level in hepatocytes of females.

A new modification of specific estrogen-binding protein (SEBP) assay in the liver was used to measure the content of this protein at different stages of ontogenesis in male and female rats after administration of testosterone propionate (TP). It was shown that liver capability to form SEBP could be initially programmed by androgens. The crucial period of the SEBP-determining action of androgens in females is not restricted, since potential capability of androgens of primary induction of SEBP may be realized both neonatally and in the course of pubertation. The emergence of SEBP in the liver of males may be the result of natural pre(neo)natal androgenization. Androgens do not play any decisive role in the control of the level of induced SEBP, inasmuch the content of SEBP in the liver of non-pubertal and pubertal males does not appreciably change after TP administration but grows with pubescence. SEBP is capable of long-term existence in the absence of androgens. The presence of the ovaries produces an inhibitory effect on the level of androgen-induced SEBP and the time of its existence after TP discontinuation. Hypophysectomy does not provoke SEBP emergence in pubertal intact and ovariectomized females but prevents its induction with androgens. Adrenal- and thyroectomy produce no influence on the SEBP-programming effect of TP or promote its spontaneous appearance in the same groups of female rats.

The effects of androgens (A), estrogens (E) and hypophysectomy on the content of an unusual rat liver estrogen-binding protein (UEBP) were studied by the differential quantitative method of the UEBP content measurement. The UEBP content was shown to increase during maturation of male rats. After A injections the UEBP content was high only in the liver of prepubertal but not of mature or immature males. Castration or hypophysectomy of mature males equally caused a decrease in the UEBP content in mature males whereas subsequent administration of A made it completely return to normal. Hypophysectomy of castrated males did not alter the UEBP content. A single injection of E provoked an appreciable reduction in the UEBP level after several days. Administration of A interfered with the inhibitory action of E after simultaneous injection of A and E and recovered the E-induced lowering of the UEBP content upon administration of A following E. Hypophysectomy of castrated males did not affect significantly the UEBP level. The UEBP content was insensitive to the direct action of pituitary factors. The pituitary is necessary for the realization of the effects of E alone but not A. It is suggested that the regulatory role of A consists in the maintenance of the constant optimal UEBP level in rat liver.

A study was made of the role of estrogens (E) in the induction and regulation of the level of specific estrogen binding protein (SEBP) in the rat liver using a differentiated quantitative method of its determination. It was shown that E could not replace androgens (A) in the primary determination of the SEPB level, neither did they prevent its A-dependent induction. Multiple administration of 0.4 microgram of estradiol (E2) caused a significant decrease in the SEPB level in intact and castrated male rats as well as in ovariectomized females with the A-induced SEPB level. Multiple administration of even 10 micrograms of E2 did not influence the SEPB level in hypophysectomized males. The rate of development of the E2 effect on the SEPB level of the mature male liver increased with the growth of the dose and duration of hormone administration. The inhibitory effect of E2 was also revealed in a single administration of 10 micrograms of the hormone. In that case the effect was observed after a 3-day lag period, and a maximum decrease in the SEPB level occurred in 6 days. The regulatory negative effect of E2 was reversible. Complete regeneration of the initial SEPB content took place 10-12 days after the development of the maximum effect of E2.

Male rat hepatocyte cultures have been obtained. The culturing hepatocytes had a stable level of some morphological and functional properties. A high level of estrogen receptors (ER) and E2-sensitive unusual estrogen-binding protein (UEBP) was found. A direct dose-dependent inhibiting effect of physiological (10(-10)-10(-7) M) concentrations of E2 on UEBP content was established in cell cultures incubated with the hormone for 3 days. Hexestrol (but not cholesterol) was found to exert a direct inhibiting effect. The inhibiting effect of E2 (10(-9) M) was observed after a 24 hour incubation of hepatocytes with the hormone but was less pronounced. In this case a significant increase in UEBP concentration in hepatocytes was noted 72 hours after the removal of E2. It is concluded that physiological concentrations of E2 can exert a direct regulatory influence on certain functions of culturing hepatocytes acting via hepatocyte ER.

The effect of some hormones of total metabolic action on a degree of sex differentiation of the liver by a specific estrogen-binding protein (SEBP) was investigated. Insulin administration did not change the SEBP level of the male rat liver. Adrenalectomy and dexamethasone administration caused no significant changes of sex differentiation of the SEBP level in the male and female rat liver. Neither did thyroidectomy cause significant changes in the SEBP level. Dose-related T3 administration decreased reversibly the SEBP level in the liver of adult male rats. The effect of T3 on the SEBP level was preserved after castration or hypophysectomy of males. T3 administration decreased a degree of determination of a raised level of SEBP in the female rat liver by androgens. STH injections were effective mainly in hypophysectomized male rats resulting, on the one hand, in an increase in the level of SEBP and creating conditions, on the other hand, for a decrease in its level caused by estradiol. It has been concluded that thyroid hormones and STH are able to be modulators of adaptive changes of sex differences of the liver by SEBP.