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J F van Uem

Publications and source records attributed to J F van Uem.

11 recordsLinked to original sources
PubMed1994

Non-competitive anti-oestrogenic activity of progesterone antagonists in primate models.

We have summarized some of the studies containing basic biological data suggesting potential therapeutic utility of the anti-proliferative activity of antiprogestins on uterine tissues. The non-competitive anti-oestrogenic effects of RU486 were examined using oestradiol-treated ovariectomized monkeys given RU486, progesterone or both. The oestradiol-induced luteinizing hormone surge of control animals was abrogated by progesterone and/or RU486. Secretory transformation by progesterone was inhibited by RU486 co-administration. RU486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) induced inhibited proliferation and secretory activity. Thus, in the presence of progesterone, RU486 is antagonistic but, in its absence, RU486 exhibits endometrial progestational effects at low doses and an anti-proliferative (anti-oestrogenic) effect at higher doses. These data encourage continued evaluation of RU486 as a potential contraceptive agent acting at the pituitary and/or endometrial level. Our study also demonstrates that after physiological oestradiol replacement therapy, oestradiol receptor concentrations rise dramatically following antiprogestin treatment; this effect was dose-dependent.

Animals↗
PubMed1990

Ooplasmic transfusion: prophase germinal vesicle oocytes made developmentally competent by microinjection of metaphase II egg cytoplasm.

Approximately one fourth of all human oocytes collected for in vitro fertilization are of immature origin. Even when these oocytes undergo nuclear maturation, fertilization, and cleavage in vitro, transfer of such embryos rarely results in pregnancy reaching delivery. We hypothesized that human embryos derived from prophase I oocytes were developmentally incompetent because they lacked a factor(s) found in in vivo matured oocytes. Using micromanipulation techniques in monkeys, we removed ooplasm from metaphase II oocytes and injected it into prophase I oocytes. After nuclear maturation, oocytes were transferred to the fallopian tube for fertilization. After ooplasmic transfusion, prophase I oocytes resulted in a delivery rate of 13%. When metaphase II ooplasm was heated or exposed to ribonuclease A before microinjection into prophase I oocytes, it lost effectiveness in conferring developmental competence.

Animals↗
PubMed1989

Contraceptive potential of RU 486 by ovulation inhibition: I. Pituitary versus ovarian action with blockade of estrogen-induced endometrial proliferation.

In previous studies, RU 486 administration arrested spontaneous folliculogenesis. To investigate the central versus peripheral effects of RU 486 on the ovarian/menstrual cycle, including endometrial proliferation, RU 486 was administered daily (10 mg/kg/day, im) from menstrual cycle day 3 or 7 to day 25 in normal adult cynomolgus monkeys receiving hMG treatment (37.5 IU/day) from days 3-8 (n = 6). RU 486 administration with hMG/hCG therapy did not inhibit ovarian response, as evidenced by steroidogenesis and ovulation. Nine of 23 oocytes retrieved by lavage or follicular aspiration at laparotomy after ovulation induction were morphologically classified as mature preovulatory status. Whereas an endometrial biopsy performed on cycle day 25 in control monkeys revealed an in phase mature secretory endometrium, histologic sections from RU 486 plus hMG/hCG treated females uniformly demonstrated atrophic to weakly proliferative endometrium on cycle day 25, despite serum estradiol levels greater than 300 pg/ml. Three months after the initial 25-day study endometrial biopsies revealed persistent atrophic endometrium, even though repeated ovulation induction with hMG/hCG therapy elevated serum estrogen concentrations. The findings prevailed whether RU 486 treatment began on cycle day 3 or 7. The intermenstrual interval was significantly (P less than 0.01) lengthened by RU 486 treatments (28.5 +/- 2.0, control vs 131.3 +/- 11.5 days, RU 486). In summary, RU 486 consistently blocked ovulation unless hCG was provided and elicited a persistent retardation of early proliferative endometrium when administered daily beginning in early or mid-follicular phase. The normal mitogenic effects of elevated ovarian estrogen secretion on endometrial tissue were quelled, uniformly resulting in amenorrhea. The long-lasting action of RU 486, causing ovulation inhibition and atrophic endometrium, may be due to the depot effect of im injection. In addition, RU 486 did not prevent ovarian steroidogenesis, ovulation or oocyte maturation when an ovulation induction regimen of hMG/hCG was given. These findings show that RU 486 prevented ovulation by diminishing pituitary gonadotropin secretion, rather than by direct effects on ovarian folliculogenesis, and induced amenorrhea by inhibiting estrogen-induced endometrial proliferation.

Animals↗
PubMed1988

[Antigestagens].

Recently potent 19-norprogestin derivatives of the RU 486-type were developed. Acting at the receptor level, these steroids are considered a major breakthrough in steroid endocrinology. Clinical studies indicate their potential use in fertility control. Besides biochemical, pharmacological and clinical aspects of the antiprogestins, the ultimate role in the therapeutic management of certain endometrial and breast cancers, endometriosis as well as induction of labour at term are discussed.

Animals↗
PubMed1988

Subcutaneous implantable infusion device for chronic intravenous pulsatile gonadotropin-releasing hormone treatment.

Preliminary data indicate the potential utility of an implantable subcutaneous device that facilitates chronic intravenous infusion of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction. GnRH distribution curves were congruent in control monkeys and those with implanted devices. Tissue tolerance was good in this brief trial. These findings suggest that use of this or a similar implantable device be considered for chronic GnRH administration in human pulse therapy.

Animals↗
PubMed1987

Preovulatory serum gonadotropin levels in hMG stimulated menstrual cycles in pregnant and nonpregnant patients.

In a group of patients undergoing in vitro fertilization, 10 pregnant and 10 nonpregnant, cycles were analysed in retrospect in relation to gonadotropin and steroid hormones. All patients were similar in terms of age, body surface area and initial stimulation protocol. The increase in follicles stimulating hormone (FSH) was significantly higher in the pregnant group through cycle day 8 as compared with cycle day 3 before stimulation. A significant increase in the nonpregnant group was never detectable; the mean FSH levels rather decreased to the baseline value during stimulation after a slight nonsignificant increase. The levels of luteinizing hormone (LH) decreased significantly in pregnant and nonpregnant patients during stimulation. No significant difference in the FSH/LH ratio between the pregnant and nonpregnant group was encountered. Although the mean serum estrogen in the follicular phase and the serum estrogen and progesteron values in the luteal phase were higher in the pregnant patients, no statistically significant difference between groups could be demonstrated, until luteal day 11. It is believed from this study, that a 15-20% increase in serum FSH levels over baseline during the early and mid follicular phase is required for adequate follicular development and steroidogenesis. The determination of serum gonadotropins in the follicular phase in patients who failed to conceive, might reveal differences, which can account for failures in hMG induced cycles.

Adult↗
PubMed1986

RU486-induced menses in cynomolgus monkeys: uniformity of endometrial sloughing.

A progesterone (P) antagonist (RU486) was administered to cynomolgus monkeys in the midluteal phase (cycle day 21 to 24), alone or in combination with P. Vehicle only was administered to other monkeys that served as controls. On cycle day 25, hysterectomy was performed on all of the monkeys. The endometrium was studied histologically in fundal, medial, and isthmic regions. RU486 induced menses in all treated monkeys; but the amount of residual endometrium was slightly higher in primates that received RU486 plus P. The effect of RU 486 on the endometrium was surprisingly homogeneous throughout the uterus. The findings demonstrate that administration of RU486 in the luteal phase induced a nearly uniform and homogeneous sloughing of the endometrium. Whereas concurrent P treatment did not prevent induction of menstruation, the depth of endometrial shedding was less than with RU486 alone.

Animals↗