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Results for “Luteolytic Effects”

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PubMed1982

Effect of embryos on luteolysis and termination of early pregnancy in sheep with cloprostenol.

An investigation of the control of the function of the corpus luteum of early pregnancy in sheep has been carried out by assessing the luteolytic effects of a dose of 100 micrograms of the synthetic prostaglandin, cloprostenol. Cloprostenol injected into 21-day pregnant sheep carrying single or multiple embryos caused luteolysis and termination of pregnancy within 2--5 days in 8 of 23 sheep. The mean numbers of corpora lutea in these ewes differed significantly from those which carried their pregnancy (1.8 +/- 0.3, SEM, vs 3.2 +/- 0.4; P less than 0.05). It appeared that the greater number of embryos, or a greater mass of embryonic tissue, afforded increased protection to the corpora lutea through unidentified antiluteolytic or luteotrophic factors. The number of corpora lutea present did not appear to be an operative factor, as the same dose of cloprostenol was luteolytic in 43 of 46 nonpregnant ewes with 1--6 corpora lutea; the 3 refractive ewes each having only 1 corpus luteum. The progesterone concentration in the plasma of pregnant ewes which underwent luteolysis following cloprostenol treatment was 0.5 +/- 0.1 ng/ml 48 h after injection, while that of the ewes remaining pregnant was significantly higher at 2.1 +/- 0.3 ng/ml. Seven of these refractive ewes which were given a second injection of cloprostenol on Day 28 of pregnancy subsequently experienced luteolysis and abortion. The corpora lutea of the remaining 8 ewes were not affected by saline injections given on Day 28, but 4 of these ewes later aborted after Day 44. It is concluded that pregnancies on ewes carrying 1 embryo can be terminated by a single dose of 100 micrograms cloprostenol given around Day 21 of pregnancy, but 2 injections given about 7 days apart may be needed when multiple embryos are present. Hormonal control of the sensitivity of the corpus luteum to luteolytic prostaglandins appears to reside in the conceptus in such a way that a decrease in sensitivity is related to the number of embryos present.

Abortion, Veterinary↗

PubMed2001

Effects of Inula viscosa leaf extracts on abortion and implantation in rats.

The anti-implantation and mid-term abortifacient effects exhibited by administration of Inula viscosa leaf extracts, were studied in rats. The aqueous extract administered i.p. on day 1-6 of gestation, totally diminished fetal implantation and caused a significant (P<0.05) reduction in the number of corpora lutea and blood progesterone levels. Meanwhile, administration on day 13-15 of gestation exhibited mid-term abortion. Furthermore, petroleum ether and dichloromethane, but not methanol, extracts exhibited pronounced abortifacient effects. The results of this study are in agreement with the traditional reputation of this plant as abortifacient. Further, the plant possesses anti-implantational and luteolytic effects.

Abortifacient Agents↗

PubMed1986

Human luteolysis--interaction between HCG and oestradiol-17beta in an in-vitro model.

Corpora lutea (CL) were excised from each of 24 women undergoing laparotomy at different and well-classified stages of the luteal phase of the menstrual cycle. Pieces were incubated for intervals between 30 min and 4 h, the incubations being carried out in the presence or absence of human chorionic gonadotrophin (HCG) and oestradiol-17beta (E2) along and in combination. Following incubation, the tissue levels of cAMP and the media concentrations of progesterone and, in certain cases, pregnenolone, were determined. HCG stimulated the production of cAMP and progesterone in CL of all ages. This effect on the formation of progesterone was significantly counteracted by E2 in CL of the early and mid-luteal phases. The addition of indomethacin to the incubation media did not alter this anti-gonadotrophic effect of E2 in-vitro. The formation of cAMP was not influenced by E2 in-vitro. These results suggest that the well-known luteolytic effect of E2 in-vivo is caused by inhibition of the gonadotrophin-stimulated synthesis of progesterone by corpora lutea, an effect mediated neither by prostaglandins nor cAMP.

Adult↗

PubMed1992

Effect of RMI 12,936, an antiprogestational steroid on decidual cell reaction and embryos in rat.

Subcutaneous administration of RMI 12,936 at a dose level of 2 mg/rat on day 5 of unilaterally pregnant rat having trauma-induced decidual cell reaction (DCR) in the contralateral uterine horn, suppresses DCR, induces resorption of implanted embryos and leads to decrease in the plasma level of progesterone. Progesterone replacement (D 5-8) in this situation reverses DCR suppressive effect of RMI 12,936 but fails to prevent resorption of implanted embryos. It is concluded that possibly the drug simultaneously exerts embryotoxic as well as luteolytic effects, but these effects are independent.

Androstenols↗

PubMed1994

Effect of antiprogestagen RU486 on both natural and prolactin-induced morphological luteolysis in rat..

Adult female cyclic rats were hypophysectomized and their pituitary glands autotransplanted beneath the left kidney capsule (Aptr) on day 1 (metestrus). To induce the luteolytic effect of prolactin (PRL) the rats were injected s.c. with 0.4 mg of 2-bromo-alpha-ergocryptine (CB154) on cycle days 12, 13 and 14. Other groups of Aptr rats were injected daily with CB154 or ethanol vehicle from day 12 to day 23. To study the role of progesterone (P) on the luteotrophic effect of PRL as well as on the natural and on the PRL-induced luteolysis, rats without CB154 treatment or with long or short CB154 treatment were injected s. c. with 2 mg of the antiprogestagen RU486 or 0.1 ml oil from day 1 to day 23. From each rat the mean weight of the corpus luteum (CL) was noted on day 24. The serum PRL level rose from day 1 to day 12 and fell thereafter by day 15 in CB154-treated rats. The serum level of PRL rose again in short term CB154-treated rats, and remained low in long term CB154-treated rats. No effect of RU486 on serum PRL levels was noted in any group. The serum P level fell rapidly as the treatment with CB154 began after day 12. Neither the rise in serum PRL after day 15 in short term CB154-treated rats nor RU486 treatment affected the P level. Treatment with RU486 did not affect the CL weight on day 24 in ethanol vehicle injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

The influence of some prostaglandin analogous on the female rat ovary and uterine tube epithelium.

The synthetic analogous of the prostaglandins are utilized in the obstetrical and gynecological therapy for multiple purposes. 4 lots with 12 nonpregnant female rats were use: the Ist received 25 g/kg/day isopropyl ester PGF2; the IInd lot received 50 g/kg/day isopropyl ester PGF2; the IIIrd lot received 50 g/kg/day optic active cloprostenol; the IVth lot was the witness lot. The medication was intraperitoneally (i.p.) administrated in a unique daily dose. Prostaglandin F2 analogous at small doses (25 micrograms/kg/day) induce vasodilating effects on the ovary blood vessels and functional luteolysis rather than structural luteolysis. Both of the prostaglandins analogous at doses of 50 micrograms/kg/day present obvious vasodilating and luteolytic effects, although the intensity of the phenomenon is not the same, cloprostenol is more active, inducing a more obvious vasodilatation and luteolysis.

Animals↗

PubMed1975

Effect of PGF2alpha in pseudopregnancy.

Eleven normal female volunteers received human chorionic gonadotropin (HCG) intramuscularly to induce a pseudopregnant state. Twenty-five milligrams of prostaglandin F2alpha (PGF2alpha) was administered intravenously at selected times during the luteal phase to demonstrate a luteolytic effect, or a local effect upon the endometrium producing early vaginal bleeding. Careful comparison of hormone levels and clinical details in these cycles showed that a) 1000 IU HCG daily does not consistently prolong the luteal phase; b) 2500 IU HCG daily does significantly prolong the luteal phase; c) HCG administration significantly increases progesterone and estradiol output in the treated luteal phase; d) prostaglandin administration at selected times during the luteal phase does not consistently decrease estradiol or progesterone output from the corpus luteum or induce early vaginal bleeding; e) prostaglandin F2alpha, a known stimulant of uterine contractility probably causes vaginal bleeding by mechanical means, as evidenced by show of menses in patients with progesterone levels elevated above normal; f) although variations in progesterone and estradiol output occurred during the hours of prostaglandin infusion, no consistent change was observed except for a compensatory rebound in progesterone output; g) prostaglandin F2alpha, in the dose utilized, is not a luteolytic agent.

Adult↗

PubMed2002

Endothelin-1 receptors and biosynthesis in the corpus luteum: molecular and physiological implications.

Endothelin-1 (ET-1), a 21-amino acid peptide was initially identified as a potent vasoconstrictor, ET-1 plays an important role in the female reproductive cycle: its quick ascent during luteal regression, ability to inhibit steroidogenesis in vitro and in vivo, combined with the observation that the luteolytic effects of prostaglandin F2alpha (PGF2alpha) were delayed by pretreatment with ET-1 receptors type A (ETA) antagonists suggest that this peptide functions as an important element of the luteolytic cascade. The observation that ETA receptor expression was inversely correlated with steroidogenesis in luteal cells; namely factors which stimulated steroidogenesis inhibited ETA receptor levels is also in accord with the inhibitory role of ET-1 in corpus luteum (CL) function. Contrary to the mature mid cycle CL, the CL of early cycle is refractory to PGF2alpha-induced luteolysis. PGF2alpha administered at early luteal phase (day 4 of the cycle) failed to increase luteal ET-1 gene expression or its ETA receptors. In contrast, both genes were markedly induced in mid cycle CL exposed to PGF2alpha. ET-1 gene is transcribed as prepro ET-1 (ppET-1) and the active form of peptide is derived from the inactive intermediate big ET-1, by endothelin-converting enzyme-1 (ECE-1), therefore alterations in mature ET-1 levels can be achieved by modulating the expression of ppET-1 and/or ECE-1. Analysis using in situ hybridization and enriched luteal cell subpopulations showed that both steroidogenic and endothelial cells of the CL expressed high levels of ECE-1 mRNA. The ppET-1 mRNA, on the other hand, was only expressed by resident endothelial cells, suggesting that luteal parenchymal and endothelial cells cooperate in the biosynthesis of mature bioactive ET-1. A significant, four-fold elevation in ECE-1 expression (mRNA and protein levels) occurred during the transition of the CL from early to mid luteal phase. This increase was accompanied by a significant rise in ET-1 peptide. Surprisingly however, ppET-1 mRNA levels remained similar during early and mid luteal phase. Collectively, these studies demonstrate that: (a) the various components of ET-1 system (ET-1/ECE-1/ETA) are dynamically and independently regulated during bovine luteal life span. (b) The CL becomes PGF2alpha-responsive only when both ppET-1 and ECE-1 genes are expressed at a level which enable an uninterrupted ET-1 biosynthesis.

Animals↗

PubMed1979

Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.

Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.

Animals↗

PubMed1975

Effect of prostaglandin F2 alpha on the ultrastructure and function of sheep corpora lutea.

Early morphological changes in the ultrastructure of CL of ewes treated with prostaglandin F2alpha were examined in relation to luteal function as judged by plasma progesterone concentration. The luteolytic effect of prostaglandin F2alpha was confirmed, but there was little synchrony between morphological and functional luteolysis. Significant changes included a decrease in the amount of smooth endoplasmic reticulum, a change in the shape of mitochondria and a decrease in the number of membrane-bound granules. There was also an accumulation of lipids.

Animals↗

PubMed1988

[Effects of prostaglandin F2 alpha on steroidogenesis of the PMSG-hCG primed rat ovary in luteolysis].

Activities of the steroidogenic enzymes involved in functional luteolysis and PGF2 alpha induced luteolysis were determined in PMSG-hCG primed immature rats to elucidate the luteolytic effects of PGF2 alpha. Plasma progesterone (P4), plasma 20 alpha dihydroprogesterone (20 alpha OHP4), in vitro production of pregnenolone (P5) from endogenous cholesterol in ovarian mitochondria (8,000 X g pellet; Mt), activities of 3 beta hydroxysteroid dehydrogenase (3 beta HSD) in ovarian microsome (105,000 X g pellet; Ms) and 20 alpha hydroxysteroid dehydrogenase (20 alpha HSD) in ovarian cytosol(105,000 X g supernatant; Sup) were determined. For the investigation of intramitochondrial transport of cholesterol, measurement of free cholesterol (FCh) of Mt and the Lineweaver-Burk plotting for cholesterol side-chain cleavage enzyme (CSCC), prepared by osmotic shock and sonication of Mt, were carried out. Functional life span of the rat corpus luteum was estimated as 12 days post hCG treatment from plasma P4. As plasma P4 decreased, concomitant increase in plasma 20 alpha OHP4 was observed. In vitro production of P5 in Mt correlated well with plasma P4 levels, indicating cholesterol side-chain cleavage reaction is the rate limiting step involved in ovarian steroidogenesis. In contrast, both values of Km and Vmax of CSCC did not change between day 7, on which the highest value of plasma P4 observed, and day 12, on which functional luteolysis was ascertained from plasma P4. Both FCh of Mt and the activity of 3 beta HSD in Ms remained unchanged during the functional life of the corpus luteum. The activity of 20 alpha HSD in Sup increased from day 10 post hCG treatment in accordance with plasma 20 alpha OHP4. These results indicate that 1) decrease in availability of FCh to CSCC within mitochondria and 2) increase in catabolism of P4 into inactive progestin, 20 alpha OHP4, may play key roles in the functional luteolysis. To compare the events observed in functional luteolysis with PGF2 alpha induced luteolysis, the animals were treated either with PGF2 alpha (1 mg/rat; s.c.), cycloheximide (5 mg/rat; i.p.; CX), or vehicle on day 7 post hCG treatment, and sacrificed 1 hour later for the analyses mentioned above. Both plasma P4 and in vitro production of P5 in Mt decreased significantly with PGF2 alpha or CX treatment, whereas the FCh of Mt and the activity of CSCC remained unchanged with PGF2 alpha treatment. Both plasma 20 alpha OHP4 and 20 alpha HSD in Sup increased with PGF2 alpha treatment. However, CX suppressed both of them.(ABSTRACT TRUNCATED AT 400 WORDS)

20-alpha-Dihydroprogesterone↗

PubMed1979

Chemical synthesis and bioassay of anordrin and dinordrin I and II.

The chemical synthesis of 2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol dipropionate (Anordrin) and the corresponding diacetate is reported. Similarly, the preparation of the 2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-estrane-2 beta, 17 beta-diol, its diacetate and dipropionate (Dinordrin I), along with the corresponding 2 beta-epimer (Dinordrin II) from 17 beta-hydroxy-A-nor-5 alpha=estran-2-one is described. In rat uterotrophic activity bioassay, the slope of ethynylestradiol differed significantly from the slopes of the other three compounds, thus vitiating potency estimates with this reference compound. Dinordrin I was 20 times more potent than Anordrin and considerably more potent then Dinordrin II. The single-dose oral antifertility effect in rats generally paralleled uterotrophic activity. Immediate postovulatory contraceptive effectiveness was assessed in adult cycling female baboons given two doses daily for 4 days. Both Anordrin and Dinordrin I showed antifertility activity worthy of further study. Moreover, a definite luteolytic effect, with depression of both plasma estrogen and progesterone levels, was observed with these two steroids.

Animals↗

PubMed2000

Production of interferon by red deer (Cervus elaphus) conceptuses and the effects of roIFN-tau on the timing of luteolysis and the success of asynchronous embryo transfer.

The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.

Animals↗

PubMed2001

Induction of luteolysis in mares by ultrasound-guided intraluteal treatment with PGF2alpha.

To evaluate the technique of ultrasound-guided luteal injection in mares, PGF2alpha was administered under ultrasound guidance to horse mares (n = 7 to 9 per group) on Day 9 postovulation via either a systemic (i.m.; zero, 0.01, 0.1, or 5 mg/dose) route or a local intraluteal (i.l.; zero, 0.01 or 0.1 mg/dose) route. The luteolytic efficacy of each treatment was determined based on post-treatment decreases in progesterone concentration, interval to uterine edema (IE) and interovulatory interval (IOI). Local administration of PGF2alpha directly into the CL consistently induced luteolysis, at doses up to 50-fold lower than the lowest effective systemic dose. Significant decreases in IOI and IE occurred in mares treated with 5 mg PGF2alpha i.m. or 0.1 mg PGF2alpha i.l., but did not occur in mares treated with 0.1 or 0.01 mg PGF2alpha i.m., 0.01 mg PGF i.l., vehicle i.l. or vehicle i.m.. Progesterone concentrations were reduced to less than 10% of pretreatment values by two days post treatment in mares treated with 5 mg PGF2alpha i.m. or 0.1 mg PGF2alpha i.l.. PGF2alpha doses of 0.1 mg i.m. and 0.01 mg i.l. were associated with smaller but significant progesterone decreases (to 66% and 46% of pre-treatment values, respectively) by two days post treatment. Progesterone values after administration of i.l. vehicle did not differ from pre-treatment values by two days post treatment, but were significantly lower (53% of pre-treatment values) by four days post treatment. Intramuscular treatment with vehicle or 0.01 mg of PGF2alpha did not significantly reduce progesterone concentrations below pretreatment values. Overall, the minimum effective luteolytic dose of PGF2alpha given intraluteally was between 0.01 and 0.1 mg. Based on the results of this study, ultrasound-guided i.l. injection appears to be a repeatable method for studying the direct effect of other chemicals on luteal function. However, the current procedure carries some risk, since three i.l. injections were associated with ovarian abscesses.

Animal Husbandry↗

PubMed1988

Control of progesterone production in small and large bovine luteal cells separated by flow cytometry.

Corpora lutea were collected from Holstein heifers on Days 10 and 12 of the oestrous cycle and the cells were dispersed with collagenase. The dispersed cells were separated into preparations of highly purified (90-99%) small (less than 20 microns) and large (greater than 25 microns) luteal cells by unit gravity sedimentation and fluorescence-activated cell sorting. Net progesterone accumulation by 1 x 10(5) small cells and 1 x 10(3) large cells during 2 and 4 h incubations, respectively, were measured after additions of LH, PGF-2 alpha, and phorbol esters, alone and in combination. Progesterone synthesis was increased (P less than 0.05) by phorbol dibutyrate (PBt2) or PGF-2 alpha (P less than 0.05) in small, but not in large, luteal cells (10.1 +/- 3.0 and 18.1 +/- 5.0 ng/10(5) cells for 0 and 50 nM-PBt2, and 19.9 +/- 3.2 and 44.2 +/- 9.3 ng/10(5) cells for 0 and 1 microgram PGF-2 alpha/ml). The previously reported stimulatory effects of PKC activation and PGF-2 alpha addition to total dispersed cell preparations are therefore entirely attributable to the small, theca-derived cells. Small cells responded to low levels of LH (9.1 +/- 1.1, 69.0 +/- 5.4 and 154.7 +/- 41.4 ng/10(5) cells for 0, 1 and 5 ng LH/ml, respectively, P less than 0.05), while large cells responded only to high levels of LH (1635 +/- 318, 2662 +/- 459 and 3386 +/- 335 pg/10(3) cells for 0, 100 and 1000 ng LH/ml, respectively, P less than 0.05). PGF-2 alpha inhibited LH-, 8-Br-cAMP- and forskolin-stimulated progesterone synthesis in the large cells (3052 +/- 380, 3498 +/- 418, 3202 +/- 391 pg/10(3) cells for 1 microgram LH/ml, and 0.5 mM-8-Br-cAMP, and 1 microM-forskolin respectively and 1750 +/- 487, 2255 +/- 468, 2165 +/- 442 pg/10(3) cells for PGF-2 alpha + LH, PGF-2 alpha + 8-Br-cAMP and PGF-2 alpha + forskolin, respectively), indicating that the inhibitory effect of PGF-2 alpha on progesterone synthesis in large cells occurs at a site distal to cAMP generation. These results suggest that the large cells are the targets of the luteolytic effects of PGF-2 alpha, while the small cells are responsible for the previously reported luteotrophic effect of PGF-2 alpha in vitro.

Animals↗

PubMed1995

Luteotrophic and luteolytic interactions between bovine small and large luteal-like cells and endothelial cells.

Endothelial cells, the most abundant cell type in the bovine CL, were shown to establish intercellular contact with steroidogenic cells of the CL. Two experimental models were used to study the involvement of endothelial cells in luteal cell function: 1) luteal slices in which the integrity and communication between the different cells were maintained and 2) pure large and small luteal-like cells, cultured separately or co-cultured with endothelial cells. The luteolytic effect of prostaglandin (PG) F2 alpha was examined in these two models. Treatment with PGF2 alpha did not alter P4 secretion stimulated by LH in young (2-4-day-old) CL slices, whereas, in slices from mature (6-12 days old) CL, PGF2 alpha significantly reduced (by 40%) the stimulatory effect of LH on P4 secretion. In pure large luteal-like cells, the effect of forskolin plus PGF2 alpha on P4 secretion did not differ from forskolin given alone after 3 or 24 h of incubation. However, when co-cultured with endothelial cells, PGF2 alpha significantly inhibited forskolin stimulation. Endothelial cells significantly stimulated P4 production from large luteal-like cells only. This effect may be attributed to the action of PGI2 secreted by endothelial cells. In summary, endothelial cells may play an essential role in luteal functions by being involved in both luteotrophic and luteolytic processes.

Animals↗

PubMed1991

Divergent effects of antiprogesterone, RU 486, on progesterone, relaxin, and prolactin secretion in pregnant and hysterectomized pigs with aging corpora lutea.

Porcine corpora lutea produce progesterone and relaxin during pregnancy and after hysterectomy. Peak amounts of relaxin are released into peripheral blood in both pregnant and hysterectomized animals on about day 113 (estrus = day 0 and term = 114), and this release coincides with an abrupt decrease in the progesterone concentration. RU 486, a progesterone receptor antagonist, was used to investigate the effects of interruption of progesterone binding to its receptor on luteal function and gonadotropin secretion of pigs with aging corpora lutea. RU 486 was administered orally to hysterectomized gilts (surgery on day 8) once a day (0800 h) on days 111-115 at two dosages (group 1, 2 mg/kg BW; group 2, 4 mg/kg BW). During 5 days of RU 486 treatment, plasma progesterone concentrations in both treated groups were markedly elevated (32 and 37 ng/ml for groups 1 and 2) compared with 22 ng/ml in the controls (group 3; P less than 0.01). PRL concentrations increased in both groups (9 and 13 ng/ml) and differed significantly from those of the controls (3 ng/ml) (P less than 0.04). RU 486 treatment delayed the time of relaxin peak to days 116.1 and 117.0 in groups 1 and 2 compared with day 114.1 in the controls (P less than 0.01). Pregnant gilts received RU 486 orally once a day (0800 h) at 4 mg/kg BW beginning on day 111 until parturition occurred. Parturition was induced on day 112.7 after only two RU 486 treatments compared with day 114.7 in the control group (P less than 0.01). Progesterone decreased abruptly from a pretreatment mean of 11 to less than 0.6 ng/ml during the 2 days that RU 486 was given compared with a shift from 12 to 6 ng/ml during the same period in the controls (P less than 0.01). The time of the relaxin peak was advanced to day 112.1 in RU 486-treated gilts compared with day 113.9 in the controls (P less than 0.01). Results from this study provide strong evidence that the antagonistic effect of RU 486 on progesterone receptor results in an abrupt increase in PRL and progesterone secretion in hysterectomized gilts with aging corpora lutea. In marked contrast with hysterectomized animals, the acute luteolytic effects of RU 486 depend on the presence of the uterus and/or conceptuses in the pig. Disruption of the regulatory loop of progesterone secretion by RU 486 alters the ability of corpora lutea to produce and release peak quantities of relaxin.

Animals↗

PubMed1989

[Clinical study on LRH-A contraception by luteolysis].

Thirty-eight healthy female volunteers, aged 26-38 years with regular menstrual cycles entered into a clinical trial for contraception with Chinese made superactive stimulatory analog of LRH i.e., (D-Ala, des-GLY-EA10)-LRH yielding luteolysis. LRH-A 1 mg a day was administered by intranasal spray from the 15th through 25th day of the menstrual cycle for 1-12 consecutive cycles. During LRH-A administration no additional contraceptive was used. Luteolysis refers to reduction in plasma progesterone and shortening of the luteal phase. The results showed that luteolysis occurred in 154/158 cycles, 4 pregnancies occurred due to faulty administration. No severe side-effects were observed during administration and apparently normal cycles occurred immediately after the withdrawal of LRH-A spray. The above data indicated that LRH-A may provide a fairly good luteolytic effect. More intensive study is required for clinical application in contraceptive practice.

Administration, Intranasal↗