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U. K. BANIK

Summary.

A single intramuscular dose of HCG (50 i.u. or more per rat) was able to induce fetal resorption and eventual termination of pregnancy when injected on Day 4 or between Days 7 and 11 of pregnancy. This dose was inactive when administered on Day 12 of pregnancy. A single large dose (500 i.u./rat) induced fetal resorption when administered even on Day 12 of pregnancy. In intact rats treated with HCG, daily doses of progesterone were unable to maintain normal implantations; in ovariectomized rats treated with HCG, daily proges. terone did succeed in maintaining pregnancy in many of the animals. It is suggested that fetal resorption and the eventual pregnancy-terminating effects of HCG in rats are mediated through the alteration of normal ovarian steroidogenesis.

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U. K. Banik and M. L. Givner

Department of Endocrinology and Immunochemistry, Ayerst Research Laboratories, P.O. Box 6115, Montreal, Canada

Ovulation can be induced in mice and rats by various types and combinations of gonadotrophins, as well as by synthetic LH-RH following pretreatment with PMSG (see Stern & Schuetz, 1970; Gosden & Readhead, 1974). The present work was undertaken to establish whether LH-RH and an analogue could induce ovulation in dioestrous mice without pretreatment with PMSG.

Adult (30 ± 5 g) virgin Swiss albino mice were maintained in an air-conditioned room (24-25°C; 45-50% humidity) and exposed to equal periods of light and darkness. The decapeptides used were: (1) synthetic LH-RH (AY-24,031): H-Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, and (2) LH-RH analogue (AY-25,205): H-Pyr-His-Trp-Ser-Tyr-d-Ala-Leu-Arg-Pro-NH-CH2-CH3. The freeze-dried decapeptides were injected i.p. in 0·2 ml of 0·1% gelatin/0·9% saline between 15.00 and 15.30 hours on the day of dioestrus which was determined from examination of vaginal smears and recognition of the

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U. K. BANIK, T. TANIKELLA and S. RAKHIT

Summary.

Ten derivatives of halo propanediol were tested orally for male antifertility effects in adult Sprague-Dawley rats. Six of these compounds were effective in inducing temporary sterility at a daily dose ranging from 2·5 to 5 mg/rat. When administered over a minimum period of 7 days, these minimum effective doses did not interfere with the mating behaviour and spermatogenesis even during prolonged medication. However, at ten times the minimum effective dose, Compounds III (1-chloro-2,3-propanediol) and VII (1-chloro-2,3-bis[tetrahydropyran-2-yloxy]propane) caused severe testicular damage and irreversible sterility, while Compound X (4-[chloromethyl]-2-pentyl-1,3-dioxolane) did not. Our studies confirm that the presence of an α-chlorohydrin group is essential in halo propanediol derivatives for antifertility effects in male rats.

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U. K. BANIK, C. REVESZ and F. HERR

Summary.

Orally active synthetic oestrogens and progestins were studied in tests to prevent pregnancy in rats. By daily administration the contraceptive effect of ethynyloestradiol and a new oestrogen, 17α-[3-furyl]-estra-1,3,5(10),7-tetraene-3,17-diol 3-acetate (AY-11483), was potentiated by three progestins, namely, chlormadinone acetate, 6-chloro-3β,17α-dihydroxypregn-4,6-dien-20-one diacetate (AY-11440) and medrogestone. AY-11483 given alone, or together with AY-11440, was more potent in preventing ovulation and implantation than ethynyloestradiol alone or in combination with other compounds. Chlormadinone acetate or AY-11440 alone were completely inactive in all the assays. The mode of action of oestrogen or oestrogen and progestin in the prevention of ovulation and implantation is discussed. In the rat, implantation seems more vulnerable to oestrogens than does ovulation.

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U. K. BANIK and M. L. GIVNER

Summary.

Pro-oestrous rats, treated with fluphenazine dihydrochloride to block ovulation, were used to compare the ovulation-inducing activity of synthetic LH-RH with one of its analogues, [d-Ala6, des-Gly-NH2 10]-LH-RH ethylamide (AY-25,205). The lowest dose of LH-RH which produced a significant response was 125 ng compared with 2·9 ng AY-25,205. Statistical analysis of the data showed that AY-25,205 was approximately thirty-six times more potent than LH-RH. Treatment with AY-25,205 also induced partial ovulation in metoestrous rats (80 or 160 ng/rat) and apparently normal ovulation in dioestrous rats (10 to 160 ng/rat). The compound (160 ng) failed to induce further ovulation in oestrous rats which ovulated during the previous night. Advancement of premature ovulation in dioestrous rats with AY-25,205 prevented mating behaviour and pregnancy during the treatment cycle. The antifertility effect of the compound disappeared during the following cycle.

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C. REVESZ, U. K. BANIK and Y. LEFEBVRE

Summary.

The oral oestrogenic activity of AY-11483 has been compared to that of oestriol and mestranol. The compound shows significant activity in the vaginal cornification test in rats and mice; however, it has a relatively weak effect in the uterotrophic assay in rats, mice and rabbits. Furthermore, like oestriol, it exerts a weak effect on the endometrium in rabbits. Based on our findings, AY-11483 should be classified as an impeded oestrogen with possible clinical application.