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A Kurischko

Publications and source records attributed to A Kurischko.

13 recordsLinked to original sources
PubMed1993

[The endocrinologic profile of metabolites of the progestin dienogest].

Two identified metabolites of the orally active progestin dienogest, the compounds STS 749 (17 alpha-cyanomethyl-11 beta,17 beta-dihydroxy-estra-4,9-dien-3-one) and STS 825 (17 alpha-cyanomethyl-estra-1,3,5(10),9(11)-tetraene-3,17 beta-diol), furthermore 4 microbially formed metabolites and 10 chemically prepared analoga of dienogest were characterized by endocrinological tests. The compounds were investigated for progesterone-receptor binding, progestational and antiprogestational, estrogenic and antigonadotropic activities, furthermore for inhibition of fertility. In no case an increased progestational activity of metabolites or analoga was found, compared to the parent substance. Therefore, it should be excluded, that dienogest acts as a prodrug. Additionally, the dosages necessary to produce the progestational effects are quite similar using oral or subcutaneous application. Therefore, a first-pass effect can be neglected. Regarding the low endocrine side effects of dienogest, the antiprogestational activity may be caused, at least in part, by metabolites.

Androgen Antagonists↗
PubMed1983

Progestagenic and antigonadotrophic activities of STS 557.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was tested for progestagenic activity in rabbits and for ovulation-inhibiting activities in rabbits and rats in comparison with levonorgestrel and, in some cases, with norethisterone acetate or chlormadinone acetate. In the immature rabbit, the endometrium transformation-inducing activity of STS 557 was about 5 times higher than levonorgestrel for both oral and subcutaneous administration. The ovulation-inhibiting effect of STS 557 was 3.5 times higher than that of levonorgestrel in the rabbit after oral administration, and about 7 times higher in the rat. After subcutaneous injection, however, the antiovulatory activity of STS 557 in rats was only about 4% of that of levonorgestrel when the ED 50 were compared.

Administration, Oral↗
PubMed1983

Interceptive activities of STS 557 in rabbits, mice and rats.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) is a interceptive agent in rabbits, mice and rats. In rats, it also shows post-implantational pregnancyterminating activity. In rabbits treated orally before mating or after ovulation for three consecutive days, it inhibited pregnancy largely at total doses of 0.08 mg/kg in the former and completely with 8.0 mg/kg in the latter case. A single subcutaneous dose of 40 mg/kg given on day 1 of pregnancy inhibited completely nidation in rats. In inhibition of pregnancy in rats could also be realized when the dose of 40 mg/kg was distributed on several days and given subcutaneously at daily doses of 5.0 mg/kg on days 1--8 of pregnancy, and even only daily doses of 2 mg STS 557/kg were needed in this respect, if animals which showed no living conceptuses were scored as "non-pregnant". STS 557 was effective in terminating pregnancy in rats, too, when given subcutaneously after implantation for 4 days at daily doses of 50 mg/kg, beginning on day 5 or on day 8 of pregnancy. The nidation inhibiting effects of STS 557 in rabbits treated pre-coitally, and in mice as well as in rats treated post-coitally were more marked than those of levonorgestrel. The interceptive and post-implantational inhibiting activity of STS 557 may be based on its antiprogestagenic properties. Luteolysis in the nidation phase can be excluded as shown by radioimmunoassay of progesterone in rats. The antigestagenic effects on the endometrium in rats were evident in the diamine oxidase assay. The acceleration of tubal egg transport, the morphological changes of the endometrium shown by scanning electron microscopy, and the effects on blastocyst transfer, all investigated in rats, suggest peripheral mechanisms of action.

Amine Oxidase (Copper-Containing)↗
PubMed1982

Further report on the endocrinological profile of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9(10)-diene-3-one (STS 557) in rodents.

STS 557, a new orally active progestin with antifertility properties has been tested for uterotrophic, antiuterotrophic, vaginotrophic, and antiovulatory effects. Further, maintenance of pregnancy in ovariectomized mice, influence on pregnancy in mice and rats, and conditioning of the immature rat uterus for decidual response were investigated. Both estrogenic and anti-estrogenic activities in mice and rats were found to be very low. STS 557 fails to maintain pregnancy in ovariectomized animals but does not interfere with pregnancy in intact mice if implantation already took place. Moreover, no effects have been found regarding the influence on the first ovulation in prepuberal rats. The biological profile of STS 557 in animals seems to make this compound suitable for use as a post-coital contraceptive.

Animals↗
PubMed1980

Embryotoxic effects of post-coital fertility inhibiting steroids.

In mice post-coital estrogens caused retardation of tubal egg cleavage, whereas post-coital progestins stimulated egg division. In rats the situation was reversed. In this species estrogens accelerated the tubal embryo development and vice versa; the progestin STS 557 arrested division of embryos resting in the tube. Normal implantation occured following transfer of early blastocysts from estrogen-treated mice to untreated mice, but not following transfer of blastocysts from untreated animals to estrogen-treated animals. This shows that post-coital estrogens do not affect the embryos directly but they disturb the physiological integrity of the endometrium required for proper implantation.

Abnormalities, Drug-Induced↗
PubMed1980

STS 557 as an interceptive in rodents and baboons.

Studies with mice, rats, guinea pigs and baboons were undertaken to define the interceptive action of the new progestin STS 557 (17 alpha -cyanomethyl-17 beta-hydroxy-estra-4.9(10)-diene-3-one) and to compare it with other progestins used in oral contraceptives. STS 557, norethindrone and norethindrone acetate reduced deciduoma formation as well as the number of implantations in mice and rats. Chlormadinone acetate and levonorgestrel when administered at the appropriate dose could not prevent early pregnancy or deciduoma formation. But in contrast to STS 557, levonorgestrel maintained early pregnancy in ovariectomized rats. On the other hand, STS 557 was ineffective as a postcoital agent in guinea pigs. When 0.4 mg STS 557 was orally administered to 37 female baboons 3 or 6 h after the mating period, only one pregnancy occurred in a total of 60 cycles investigated (controls: 11 pregnancies in 12 cycles investigated). The results are discussed in view of the development of an interceptive method based on STS 557.

Animals↗
PubMed1980

STS 557, a new orally active progestin with antiprogestational and contragestational properties in rabbits.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4.9(10)-diene-3-one) is a potent progestin. This compound was 10 times as potent as the standard levonorgestrel as judged by the classic Clauberg-McPhail Assay. The antiprogestational response is significant when STS 557 treatment starts 2 days before progesterone administration. It does not disturb the priming activity of estradiol. This compound alone is adequate for endometrial priming. Early pregnancy is maintained in ovariectomized does. Administration on day 1 of pregnancy reduces the number of implantations. In comparison with chlormadinone acetate and d-norgestrel, only STS 557 treatment causes complete inhibition of egg fertilization.

Animals↗
PubMed1980

Effects of levonorgestrel and STS 557 on testis in rodents.

In immature male Wistar rats levonorgestrel and STS 557 (17 alpha-cyanomethyl-17 beta-hydroxyestra-4,9(10)-diene-3-one) reduced testicular growth, testicular DNA contents and plane of tubular cross-section in a dose dependent manner. In this respect, STS was less active than levonorgestrel. In immature castrated male rats the LH-suppressing effect of STS 557 was about 15 times lower than that of levonorgestrel. The results suggested that peripheral inhibitory effect of the two progestins was coupled with central LH suppression. On the other hand, in mating tests with male hybrid mice STS 557 possessed high fertility inhibiting activities in comparison to levonorgestrel and chlormadinone acetate. Limited dissociation has been shown between fertility inhibition and mating rate. All changes were reversible. Findings are discussed in view of development of male contraceptives.

Animals↗
PubMed1979

Direct evidence for the involvement of prostaglandin F2 alpha in the first step of estrone-induced blastocyst implantation in the spayed rat.

The effect of prostaglandin F2 alpha (PGF2 alpha) on blastocyst implantation in spayed rats has been studied. In preliminary experiments, the first implantation sites were observed 8 - 12 hours after a single injection of estrone in ovariectomized and progesterone-conditioned rats. Intraluminal instillation of PGF2 alpha into the right uterine horn 8 - 10 h after the estrone injection increased the number of implantation sites. Even treatment with PGF2 alpha without previous estrone injection induced the first step of blastocyst implantation as shown by uterine dye site reaction (Niagara-blue test). The results are discussed with regard to the possible role of PGF2 alpha in the regulation of the blastocyst implantation processes in the rat.

Animals↗
PubMed1978

Relationship between uterotrophic and interceptive activities of steroidal estrogens.

The steroidal estrogens ethinylestradiol, mestranol and the synthetic "impeded" estrogen derivatives STS 456, STS 593 and J 628 were studied for their postcoital antifertility activity and estrogenicity in mice, rats and rabbits. Results of these studies suggest a positive relationship between these two biological endpoints with the exception of the findings in rats. As seen in uterotrophic--anti-implantation ratio, in view of only one species it is possible to dissociate the interceptive and the unwanted uterotrophic activities. The profound species differences in the effects of exogenous estrogens on the nidation phase are discussed.

Animals↗
PubMed1977

Androgen-dependent fighting behaviour in male mice.

The influence of testosterone propionate, 17 alpha-methyl-testosterone and cyproterone acetate on isolation induced fighting behaviour of mice was studied in a simple testing procedure. Decreased aggressiveness has been established in mature, sexual experienced and isolated male mice both following castration and administration of the antiandrogen cyproterone acetate, respectively. Replacement therapy with testosterone propionate s.c. and 17 alpha-methyl-testosterone p.o. has been shown to restore the decreased level of aggresiveness after castration.

Aggression↗