[Criteria of the sensitivity of Zajdela and Morris hepatoma cells to glucocorticoids]. / Kriterii chuvstvitel'nosti kletok gepatom Zaidela i Morrisa k gliukokortikoidam.

Glucocorticoids induce tyrosine aminotransferase synthesis in 7777 Morris hepatoma but fail to do so in Zajdela hepatoma. This internal property indicates the resistance to the hormone. However, both hepatoma cell lines do respond to the triamcinolone acetonide in a similar way, as judged by some other criteria, e. g. interaction with the immobilized hormone on the inert carrier, adhesion to glass and kinetic parameters of alkaline phosphodiesterase I activity. Moreover, both cell types respond to glucocorticoids by modification of synthesis of some proteins, as revealed previously by two-dimensional electrophoresis. The results show that in case of tumour cells which retain their specific receptor apparatus but do not respond to glucocorticoids by usual criteria, the conclusion whether tumour cells are hormone-sensitive or not has to be drawn from the analysis of their multiple response judging by several assays.

[Specificity characteristics of estrogen interaction with the cytoplasmic receptors of the uterus and oviducts in green monkeys (Cercopithecus griseus)]. / Kharakteristika spetsifichnosti vzaimodeistviia éstrogenov s tsitoplazmaticheskimi retseptorami matki i iaitsevodov zelenykh martyshek (Cercopithecus griseus).

The specificity of interaction in Cercopithecus griseus uterus and oviduct cytosol receptor systems with 14 estrogenic substances has been characterized. It was shown that the activity of steroid-receptor interaction was mainly due to presence of hydroxyl groups in C3- and C17b-positions. The nearest environment of these functional groups in molecules affected also the affinity of steroids to the systems investigated. Analysis of the cytosol estrogen-receptor system specificity from Cercopithecus griseus, guinea pig, human uterus and oviduct showed the general pattern of the estrogen binding to the above-mentioned systems. Similarity was also noted between these Cercopithecus griseus and human estrogen-receptor systems.

The specificity of the human uterine receptor.

The aim of the present study was to assess the contribution of different parts of natural and synthetic steroid molecules in their binding to high affinity oestradiol receptor preparations obtained from whole human uteri. Fifty-five compounds were used in the study of which 38 contained the steroid nucleus. The affinity (in terms of association constants) of the compounds for the receptor was determined from competitive studies with radioactive oestradiol. As a consequence the compounds could be grouped according to their association constants for the receptor. The contribution of the individual functional groups of the steroid molecule to the binding process was analysed. The preliminary quantitative evaluation of the contribution was derived from the equation: log K=logdeltaKs + sigmalogdeltaKF where K8 is the contribution of the basic 1,3,5-(10)-oestratriene skeleton, KF the associated functional groups and K the affinity constant for the entire molecule. The main positive contribution in the binding is provided by skeleton and the 3-hydroxyl group. It is concluded that functional groups present at either the 3 or 17 position act independently of each other in the binding process. The possible synergism between the functional groups and the steroid skeleton is discussed.

PIP: This study analyzes the role of the functional regions of the estrogen molecule in the interaction with receptor preparations obtained from the whole human uteri. Radioactive estradiol compounds and 55 nonradioactive compounds were used in the study. 38 of the 55 compounds contained the steroid nucleus. Human uteri obtained from postmenopausal women suffering from prolapse were homogenized and centrifuged, and then analyzed for estradiol binding. The affinity, expressed in terms of association constants, of the competing compounds was determined from the formula by Ekins et al. (1968). The association constants were subdivided into compliments of molecular fragments for the quantitative evaluation of the significance of the different steroid functions according to a logarithmic equation. Competition studies were conducted among the radioactive estradiol, receptor preparations, and the competing compound at 5 concentration levels. The findings show that the presence of functional groups enhances or reduces the binding of various compounds to the receptor system. There is a significant enhancement of binding only when 3 or 17 beta hydroxyl groups are present. The suggested mathematical calculations of individual functional group increments appear to be an effective tool in the study of estrogen/receptor interaction.

[Characteristics of the estrogen receptor system of the guinea pig uterus]. / Kharakteristika éstrogenretseptornoi sistemy matok morskikh svinok.

Physico-chemical parameters of estradiol-receptor interaction in guinea pig uterine cytosol (velocity constants of association and dissociation, half-life time of estradiol-receptor complex, and the value of free energy change) were studied. The number of receptor sites per cell was calculated. It was shown that under conditions of different degree of approximation to the equilibrium, the affinity percentage in the system under study remained unchanged for the majority of steroids, this pointing to the achievement of equilibrium in these cases. The steroid affinity to the analyzed R-system depended on presence of intact 3- and 17beta-hydroxils with somewhat greater significance of 3-(phenolic) hydroxil of steroid molecule.

[Study of the specificity of the estradiol-binding system in the uteri of guinea pigs]. / Izuchenie spetsifichnosti éstradiolsviazyvaiushchei sistemy matok morskikh svinol

The authors analyzed the affinity of the steroids belonging to the estran series to the estradiol-binding system of the guinea pig uteri. The presence of free hydroxyl groups in positions 3 (phenol) and 17beta and their interorientation proved to determine the interaction with the recptor system of the guinea pig uterus. The data obtained indicated that the biological activity of the steroids was determined by the peculiarities of their structural interaction with the receptor systems of the uteri.

[The biological role of estriol]. / K voprosu o biologicheskoi roli éstriola

It was demonstrated on the uteri of women and guinea pigs that estriol (in vitro) possessed a marked affinity to the estradiol-binding system of human and guinea pig uteri; the activity of steroid-receptor interaction of estriol in vitro constituted 9.4% for guinea pigs and 17% for man in relation to the estradiol activity. Administration of estriol to guinea pigs in vivo in a dose of 0.25-0.5 mg led to a sharp reduction of the estradiol-binding capacity of the receptor system of the uterus. It is supposed that there existed a competitive relationship between estradiol and estriol for binding with the active centres of the receptor proteins of the uterus.