Browsing by Author "FORCELLEDO, ML"

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    ADDITIVE EFFECT OF RU-486 AND ANORDRIN ON PREGNANCY INTERRUPTION IN THE MOUSE
    (1993) FORCELLEDO, ML; CARDENAS, H; CROXATTO, HB
    The effect of various doses of anordrin and RU 486, alone or combined, on serum progesterone (P) levels, fetal resorption, and recovery of ovulation was studied in mice. Each drug was given as a single sc injection on day 7 of pregnancy and autopsy was performed on days 8, 9, or 11. Serum P was normal at 24 h but fell significantly 48 h after treatment with anordrin (0.05 mg). Doses of 0.05 or 0.2 mg anordrin were effective in interrupting pregnancy in 30% and 70% of pregnant mice, respectively. RU 486, 0.01 mg per mouse, induced a pronounced decrease of P levels 24 h after treatment and interrupted pregnancy in 50% of pregnant mice. The combined treatment with submaximal doses of anordrin plus RU 486 did not further decrease P levels, but increased the proportion of mice with fetal resorptions to 90%. The combination of small doses of anordrin with RU 486 had an additive effect on pregnancy termination. The additive effect required a dose of RU 486 above the threshold level. Direct observation of aborted fetuses indicated that the resorptive process occurred earlier with RU 486 than with anordrin. Recovery of ovulation was associated with pregnancy termination in a high proportion of mice treated with either drug or their combination.
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    EFFECTIVENESS OF DIFFERENT ESTROGEN PULSES IN PLASMA FOR ACCELERATING OVUM TRANSPORT AND THEIR RELATION TO ESTRADIOL LEVELS IN THE RAT OVIDUCT
    (1986) FORCELLEDO, ML; DELACERDA, ML; CROXATTO, HB
    Elevations of circulating estradiol (E2) levels due to administration of exogenous E2 accelerate embryo transport through the genital tract in pregnant rats. This study relates oviductal embryo transport to tissue E2 levels associated with blood E2 oscillations of differing profiles. Plasma E2 pulses differing in rate of increase, amplitude, and duration were achieved through various schedules of iv and sc E2 administration. Rats on the first day of pregnancy received a total dose of 5 .mu.g 17.beta.-E2 by short (10-15 min) or long (200-300 min) term iv infusions. Some animals were used to monitor blood and tissue levels of E2 (oviduct and diaphragm). Others were killed 24 h after treatment to assess number of embryos recovered. Fast iv infusions caused brief, high amplitude (> 1000 pg/ml) E2 oscillations which were ineffective in eliciting accelerated embryo transport. The longer iv infusions produced lower but sustained elevations of circulating E2 levels comparable to those achieved by sc administration and were associated with accelerated embryo transport. The oviductal E2 concentration during and after a short iv infusion was never lower than that associated with a sc injection. The lack of response to a brief, high amplitude increase in circulating E2, therefore, could not be accounted for by decreased tissue content of the hormone. These results indicate that when the total mass of E2 administered is kept constant, the magnitude of embryo transport acceleration is positively correlated with the duration and negatively correlated with the amplitude and/or slope of increase in circulating estrogen. Since different tissue content of E2 does not account for the response or no response observed it follows that the geometry of E2 oscillations in plasma has a signal value for the target cells which acts independently from the bioavailability of the hormone.
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    EFFECTS OF RU486 ON THE OVARIAN RESPONSE OF IMMATURE RATS TO PREGNANT MARES SERUM GONADOTROPIN OR DIETHYLSTILBESTROL
    (1994) FORCELLEDO, ML; LEIVA, L; CROXATTO, HB
    The purpose of this study was to further investigate the role of progesterone in follicular development induced by pregnant mare serum gonadotrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, using RU486 to prevent the receptor-mediated actions of progesterone. Intact or hypophysectomized 26-day-old rats received either a single injection of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or without 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the ovarian weight gain, the ovarian and circulating concentrations of progesterone, the concentrations of immunoreactive and bioactive LH and the number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response following PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysectomized 24 h before initiating treatment or in intact rats where ovulation was blocked with chlorpromazine. The ovarian weight gain, the development of antral follicles and the increments in tissue and plasma progesterone concentrations and luteinizing hormone (LH) plasma concentrations elicited by DES in intact rats, were further increased by concomitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited by RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in response to HCG. These results show that ovarian growth and follicular development induced by exogenous gonadotrophin or oestrogen in the immature rat are enhanced by RU486 and that this synergistic effect of the progesterone receptor blocker is either pituitary-mediated or requires the permissive action of a pituitary factor. Overall they support a negative effect of progesterone on follicular development in the rat.
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    INCREASED SECRETION OF ADRENAL PROGESTERONE EXPLAINS THE LACK OF RESPONSE OF OVIDUCTAL EMBRYO TRANSPORT TO A SHORT INTRAVENOUS-INFUSION OF ESTRADIOL IN THE RAT
    (1990) MORAN, FM; FORCELLEDO, ML; CROXATTO, HB
    Administration of estradiol (E2) as a single subcutaneous injection, but not as a short intravenous infusion (< 150 min), accelerates oviductal embryo transport in pregnant rats although the first mode determines lower E2 circulating levels. Since progesterone (P) can antagonize the effect of E2 on embryo transport we examined the circulating P levels under these two modes of E2 administration.
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    OVUM TRANSPORT IN PREGNANT, PSEUDOPREGNANT, AND CYCLIC RATS AND ITS RELATIONSHIP TO ESTRADIOL AND PROGESTERONE BLOOD-LEVELS
    (1981) FORCELLEDO, ML; VERA, R; CROXATTO, HB
    The time of passage of ova from the oviduct to the uterus and the systemic plasma levels of estradiol [E2] and progesterone [P4] were investigated in pregnant and pseudopregnant rats, and in rats with regular 4-day cycles. The relationships between ovum transport rates and steroid levels in plasma in these 3 physiologic conditions were examined. The day following proestrus was designated day 1 in the 3 groups. The number and distribution of ova were similar in the 3 physiologic conditions during the first 3 days, but significant differences appeared thereafter. The major shift in the distribution of ova between oviduct and uterus occurred between days 3 and 4 in cycling rats and between days 4 and 5 in pregnant and pseudopregnant rats. The total number of ova recovered decreased significantly on day 4 in cycling rats, on day 5 in pseudopregnant rats, and remained unchanged in pregnant animals. Differences in plasma E2 levels did not reach statistical significance. P4 concentration in plasma was significantly higher in pseudopregnant than in pregnant rats on days 2 through 5, and it was significantly lower in cycling rats in comparison with the outer groups on days 3 and 4. The E2/P4 ratio differed between groups from day 1. The time of passage of ova from the oviduct to the uterus is subject to physiologic regulation in the rat; postovulatory changes in sex steroid levels in plasma may contribute to this regulation.
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    SUBCELLULAR HYPOTHALAMIC FRACTIONS ACTIVE ON OVULATION AND LUTEINIZING-HORMONE RELEASE IN RAT
    (1977) FORCELLEDO, ML; LASTRA, MDL
    Nuclear, microsomal and cytosol fractions were obtained from hypothalamic cells by differential centrifugation in sucrose solutions of different molarities. The nuclear fraction (NF) from immature female rats had an inhibitory effect on ovulation induced with pregnant mare''s serum (PMS) in immature rats and with luteinizing hormone (LH) in chlorpromazine (CPZ)-treated proestrous rats. The microsomal fraction from the same rats increased both types of ovulation. Nuclear and microsomal fractions obtained from immature male rats were inactive on ovulation. Cytosol fractions were inactive. NF active to inhibit ovulation significantly reduced the release of LH induced with synthetic LH-RH in immature male rats and in chronically castrated male rats primed with testosterone (T).