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The estrogenic or uterotropic (UA) and contraceptive (CA) activity of two modified steroids representing 17-R-oximino-9 alpha-oxy-11 beta-nitroxyestrone derivatives (compounds I and II) was experimentally studied by oral administration in female rats in comparison to ethynylestradiol (EED) and mestranol. Compounds I and II showed significant UA (about half that of EED and mestranol) and a pronounced contraceptive effect (exceeding that of mestranol). The dissociation of the drug effects for CA is also indicated by the index of contraception (IC) or the CA/UA ratio. The administration of compounds I and II did not lead to a loss of animals in the acute toxicity tests on female mice.

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Comparative study of the effect of two groups of C-ring transformed oestrogens on the reproductive system was conducted in experiments on female rats. 11-Nitrate-9 alpha, 11 beta-dioxyethynylestadiols (I-IV), 11-nitrate-9 alpha-oxyesterons (V-VII), and 11 formiate-11 beta-oxyethynylstadiol (VIII) were given per os to the rats. As compared to ethynylestradiol (EE), compounds I-IV demonstrated 4-10 times higher oestrogenic activity and 11-23 times higher contraceptive activity. 11-Nitrate (V-VII) proved to be less active oestrogens (77-91% of EE activity) but its contraceptive effect was equal to or exceeded that of EE. The oestrogenic activity of 11-formiate (VIII) was three times higher than that of EE, but its contraceptive effect was only 50% of the effect of EE. The higher contraceptive effect of compounds I-IV in comparison to their oestrogenic activity allows these oestrogens to be considered perspective substituents of EE among the oral contraceptives. In oral administration of compound I alone or compounds I and IV together with gestagen acetomepregenol (AMP), inhibition of luteinizing hormone release was stronger and more prolonged than in administration of EE alone or in combination with AMP. This effect may be considered to be one of the possible mechanisms of the activity of 11-nitrate oestrogens.

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The experiments on 715 adult non-inbred female rats and 111 Wistar male rats have established that the estrogen 11-nitrate of 3-acetoxy-9 alpha,11 beta-dioxyestra-1,3,5(10)-trien-17-one (11-nitrate of dioxyestron (NDE-As) has an oral contraceptive activity which is equal to ethynylestradiol (EE). A combined 14-day administration of NDE-As with various gestagens produces a higher contraceptive effect that does EE used in combination with the same gestagens. A 30-day use of NDE-As with combined acetomepregenol (AMP) results in a more significant and prolonged secretion of luteinizing hormone than does the EE-AMP combination. Unlike ethynylestradiol, NDE-As has no hypertriglyceridemic effect when given in oral doses of 0.25 and 1.25 mg/kg body weight.

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A study of the effects of 9 alpha-hydroxy-11 beta-nitroxy analogs of estrone and its acetate has shown that the insertion of 9,11-hydroxynitrate grouping in the estrogen molecule increased considerably antigonadotropic activity, determined by the inhibiting testicular growth effect, and the duration of uterotropic action in administration per os as compared to similar indices in subcutaneous injections. Dissociation of antigonadotropic and uterotropic activity was also noted in injection of the analogs in the stomach as a result of an increasing antigonadotropic effect. Experiments were performed on immature male and female rats.

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Luteinizing hormone (LH) and prolactin blood plasma levels and LH level in the pituitary of alcoholic male rats were studied Alcoholic rats (heavy drinkers) have revealed hyperprolactinemia and inadequate LH secretions. The possible role of gonadotropins in the development of hypogonadism in alcoholic rats is discussed.

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Two synthetic estrogens, STS 456 and STS 593, with noteworthy post-coital antifertility properties in the rat were studied for their estrogenic, antiestrogenic, progestagenic, antiprogestagenic, antigonadotrophic, androgenic and antiandrogenic effects in laboratory animals. Beside their weak estrogenic activity which corresponds to their slight affinity to the uterine estrogen receptor in the rat, both steroids show remarkable antiestrogenic effects. No progestagenic, androgenic and antiandrogenic effects were found but STS 593 showed some antiprogestagenic activity. The antigonadotrophic efficacy of STS 456 was relatively high while STS 593 was scarcely active. The results are discussed with respect to possible application of these drugs for interceptive purposes.

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The effect of 17 beta-estradiol and polypeptides of hypophyseal origin (prolactin, adenohypophysis cell culture secretion products) on the development of 5-day rat embryos in vitro was studied. Preimplantation rat embryos grew and developed normally in medium 199 enriched with 10% embryonic calf serum. The addition into this medium of estradiol in the concentrations of 10(-6) M, 10(-8) M or prolactin (0.01 micrograms/ml) did not produce an injuring effect on the growth of embryos incubated in vitro. A clear embryotoxic effect was noted in the incubation of embryos in a medium with high concentrations (0.1-1 microgram/ml) of prolactin or in a 3-day culture of rat adenohypophyseal cells. It may be inferred that the inhibitory effect of high doses of prolactin on embryo development is one of the possible causes of the embryotoxic effect of adenohypophysis cell culture secretion products.

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The synthesis of retro-analog of methionine-5-enkephalin was performed. This peptide is an isomer of the natural methionine-5-enkephalin, but differs from it by opposite direction of peptide linkages between the amino acid residues. The influence of retro-analog on prolactin secretion was studied both in vivo and in vitro. The retro-analog was found to stimulate the prolactin secretion more effectively than methionine-5-enkephalin.

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When administered subcutaneously to male rats, the novel peptides retromet-enkephalin and retro-leu-enkephalin stimulated prolactin (PRL) release less powerfully than morphine but somewhat greater than met-enkephalin. Leu-enkephalin did not affect PRL secretion in vivo. Neither morphine nor any of opioid peptides under study were able to stimulate basal or the dopamine-inhibited PRL release from cultured adenohypophyseal cells of male rats. It is concluded that stimulatory effects of opiates and opioid peptides on PRL secretion in rats are mediated via the hypothalamus or some other neural structures.

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A series of bromo- and silyl-derivatives was studied in experiments on immature female rats in vivo and in vitro. All the estrogens studied were conventionally divided into 4 groups according to their ability for concurrent binding with the rat uterus cytosol receptors and their specific bioeffect: equally concurrent and bioeffective compounds (estrone, ethynyl estradiol); slightly concurrent substances with a pronounced uterotropic action (4-silyl estrogens, mestranol); little effective compounds with 4 to 8% of estradiol concurrent activity (2- and 4-bromo-and silyl estradiols, estriol); compounds, not having concurrent and biological effects (2-silyl estrones, 4-bromoestradiol diacetate).

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Comparative study of the estrogen properties of 2- and 4-brom and silyl-substituted estradiol administered subcutaneously and orally was carried out on sexually immature female rats. In comparison with initial estrogen, estradiol, silyl-group (SiMe3) substituted in the 4th position diminished the estrogen activity after subcutaneous injection but improved it considerably when given orally. Introduction of silyl radical in the 2nd position or of bromine in the 2nd and 4th positions of the estradiol molecule led to practically complete loss of the estrogenic activity irrespective of the method of administration of these compounds.

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Estrogen (in uterotropic test on sexually immature female rats), antifertile (in experiments on sexually mature pregnant female rats), and antigonadotropic (in a test on sexually immature male rats) properties of some 2- and 4-bromine and silylsubstituted estradiols were compared in oral administration. 4-silylestradiols expressed marked antigonadotropic effects equal by activity to mestranol standard, and reduced as compared with the standard antifertile and estrogenic properties. 2- and 4-bromide and 2-silylestradiols were weakly active or inactive oral estrogens and possessed no antifertile properties.

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Experiments were conducted on sexually-immature female rats, ovariectomized mice and castrated male rats. Hormonal properties of some 11-azaestran were studied. As shown, introduction of azafunction into the position of the 11 molecule of the steroid sharply reduced the hormonal activity, irrespective of other functions in the molecule determining the reference of the steroid to the estron, estradiol, or 19-nortestosterone series.

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Experiments were conducted on castrated male rats. The effect of antiandrogen 17,17-dimethyl-18-norandrostadien-4,13-one-3 on the androgenic and myotrophic activity of testosterone and of some of its modified analogues, preparations with anabolic action, was studied. The intensity of the antihormonal effects depended not only on the antiandrogen dose used, but also on the dose of the agonist preparation. The author suggests a modification of the method used to assess the biological action of antiandrogens, consisting in a single administration of the "anabolic" preparation with a prolonged action and a 7-day administration of antiandrogen to castrated animals.

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The authors tested a new biological model for the quantitative determination of the anabolic effect of steranobols of prolonged action. The principle of the method consists in creation of an isolated overload of the skeletal muscles of the shin (m. soleus and. m. plantaris) following section of the tendons of their synergist--m. gastrocnemius in rats, with the subsequent recording their weight gain caused by the administration of anabolic steroid. The method is simple, sensitive and permits to use the animals of different weight and sex without subjecting them to castration.

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The immobilized form of proteases complex of Str. griseus actinomycete is obtained by means of glutaric aldehyde with aminoethyl cellulose. Hydrolysis of synthetic substrates showed that the system of peptide hydrolases is bound, but the ratio of activities as compared to the initial proteolytic complex changes, pH-optimum of the total proteolytic activity, pH- and temperature optima of stability are not changed with immobilization. On the whole no essential stabilization of the complex was observed. After five repeated cycles of the immobilized form utilization of the activity loss accounts for 40-60%.

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