Treatment of normal women with oestradiol plus progesterone prevents the decrease of leptin concentrations induced by ovariectomy

To study the role of oestradiol and progesterone in the secretion of leptin, 21 normally ovulating women were recruited from those scheduled for ovariectomy plus hysterectomy performed in mid-follicular phase of the cycle. Seven of the women were used as controls and received no hormonal treatment post-operatively. Another seven women received oestradiol (oestradiol group) and the remaining seven women received oestradiol plus progesterone (oestradiol plus progesterone group). Serum leptin values showed a temporal but significant increase 24 h after the operation and were significantly correlated with the cortisol and progesterone values, which increased temporarily at 12 h. At that time a marked decline in oestradiol concentrations was seen. After the temporal increase, leptin values in the controls and the oestradiol group decreased significantly up to day 4 (P: < 0.05), while in the oestradiol plus progesterone group they increased (P: < 0.01) and were significantly higher than in the other two groups (P: < 0.05). Body mass index (BMI) was the most important variable accounting for the changes in leptin values post-operatively, but in the oestradiol plus progesterone group progesterone correlated significantly with leptin independently of BMI. These results suggest that progesterone and cortisol can stimulate leptin secretion in women regardless of oestradiol concentrations.     

Termination of early pregnancy with ZK 98, 734: pharmacokinetic behaviour and clinical effect

The antiprogestin RU 486 (mifepristone) is highly effectivein inducing early abortion in women only if the compound iscombined with a prostaglandin analogue. A new related antiprogestin,ZK 98, 734, has been reported in animal studies to be much morepotent as an abortifacient than mifepristone, concomitant withless antiglucocorticoid activity. The aim of the present two-centrestudy was to explore the abortifacient efficacy and plasma concentrationsof ZK 98, 734 in women seeking abortion. A total of 96 pregnantwomen with amenorrhoea of <49 days were treated with oraldoses of 12.5, 25, 50 or 100 mg ZK 98, 734 twice daily for 4days. The overall rate of complete abortion and continuing livepregnancies was 68 and 20% respectively, i.e. results comparablewith treatment with mifepristone alone. No dose-response relationshipwas noted. In patients with complete abortion, signs of lutealsysfunction in terms of oestradiol and progesterone productionwere evident on the fourth treatment day, in contrast to patientswith failures. Increased amounts of cortisol and prolactin werefound during treatment both in successfully treated patientsand failures, whereas aldosterone values remained unaffected.The effect on cortisol may indicate some antiglucocorticoidactivity in the human. The concentrations of ZK 98, 734 in peripheralblood after 25, 50 and 100 mg twice daily for 4 days were similar.The values were slightly above 0.5µmol/l on the secondday of treatment. Maximal concentrations of 0.7 µmol/lwere seen on treatment day 4. Plasma concentrations of ZK 98,734 did not differ in cases of complete abortion and failures.In conclusion, the abortifacient efficacy in relation to doseof the new antigestaged ZK 98, 734 does not essentially differfrom that of mifepristone treatment alone.     

Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone

The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.     

Effect of feeding on the diurnal rhythm of plasma cortisol and adrenocorticotrophic hormone concentrations in the pregnant ewe and sheep fetus.

The effects of two different feeding regimes on the 24 h profiles of maternal and fetal plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were studied in eight pregnant ewes between 123 and 144 days of gestation. Once daily-fed ewes (n = 4) received 1 kg of lucerne-chaff at 11.00 h, and multi-fed ewes (n = 4) received 100-200 g of lucerne-chaff at 09.00, 11.00 and 13.00 h and then 150 g until 09.00 h the following day. There were significant differences between the two feeding groups in the 24 h profile of maternal plasma osmolality; once daily feeding at 11.00 h was associated with a peak in maternal plasma osmolality at 15.00 h whereas maternal plasma osmolality reached plateau levels at around 17.00 h in the multi-fed group. There were also differences between the two feeding groups in the 24 h profiles of maternal and fetal plasma glucose. Maternal and fetal plasma glucose reached peak concentrations at 19.00 h in the once daily-fed ewes in contrast to the multi-fed group, where a plateau in maternal and fetal plasma glucose was reached between 19.00 h and 09.00 h the following day. A significant diurnal variation in the plasma concentrations of cortisol was present in the once daily-fed ewes from 123 days gestation and in their fetuses after, but not before, 135 days gestation. Plasma cortisol peaked at 11.00 h in the ewes and at 13.00 h in the fetuses of this group. In the once daily-fed group there was also a significant diurnal variation in maternal and fetal plasma ACTH; plasma ACTH concentrations were highest at 11.00 h in the ewes aged between 123 and 144 days and in fetuses after 135 days gestation. In the multi-fed group, whilst ACTH was highest at 09.00 h in the ewes and at 13.00 h in the fetuses, there was no significant diurnal variation in the plasma concentrations of cortisol in the ewes or fetuses of this group at any stage between 123 and 144 days gestation.     

Menstrual-like changes in mice are provoked through the pharmacologic withdrawal of progesterone using mifepristone following induction of decidualization

BACKGROUND: Cyclic shedding of the endometrium is unique to menstruating species, and mouse menstruation models by physiologic progesterone withdrawal have been previously reported. Since progesterone action ablated pharmacologically may provide more insight into the mechanism of action, a mouse menstruation model using mifepristone was established. METHODS: Mifepristone was administered following oil-induced decidualization in ovarectomized mice primed with hormones. Morphology, hormone levels, leukocytes and apoptosis were evaluated over a period of 48 h after treatment. Vaginal smears were used to monitor bleedings. RESULTS: Mifepristone induced menstrual-like changes. Tissue breakdown was drastic by 16 h, and the decidual zone was shed by 24 h while the mice bled. The endometrium regenerated from 24 h onwards and became completely restored by 48 h. These results are consistent with previous reports. However, although progesterone levels remained constant, estradiol levels increased after the treatment. The CD45(+) cells showed two peaks of increase at 16 h (breakdown phase) and 32 h (regeneration phase) (Leukocyte levels also increased in the unstimulated horns, but no breakdown changes occurred there). Moreover, apoptosis drastically increased by 16 h concurrent with tissue destruction. These results differed from those of the physiologic withdrawal models. CONCLUSIONS: The pharmacologic withdrawal of progesterone by mifepristone successfully provoked a menstrual-like process in mice after artificial decidualization.     

Correlation of endocrine profiles with bleeding patterns during use of Nestorone contraceptive implants

The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (相似文献   

Nitric oxide reverses prostaglandin-induced inhibition in ovarian progesterone secretion in rats.

The present studies were undertaken to determine whether nitric oxide (NO) is involved in the regulation of ovarian progesterone and oestradiol secretion in rats. Immature female Sprague-Dawley rats at 27 days of age were injected s.c. with 4 IU pregnant mare's serum gonadotrophin (PMSG) and were killed 72 h after the injection. The ovaries were collected, weighed and cultured in Dulbecco's modified Eagle's medium containing saline, NO donor, NO synthesis inhibitor or prostaglandin F2 alpha (PGF2 alpha). After 24 h culture, the medium concentrations of progesterone and oestradiol were measured by radioimmunoassay. Results showed that: (i) diethylenetriamine (DETA)/NO (1 x 10(-6), 1 x 10(-5), 1 x 10(-4) M), an NO donor, caused a dose-dependent increase in progesterone synthesis (355 +/- 43, 443 +/- 46, 647 +/- 55 ng/g ovary respectively, P < 0.01) with a concomitant decrease in ovarian oestradiol secretion (408.1 +/- 50.7, 272.9 +/- 28.2, 132.6 +/- 34.6 pg/g ovary respectively, P < 0.01); (ii) neither progesterone nor oestradiol concentrations in the culture medium were altered by DETA without NO; (iii) NG-nitro-l-arginine methyl ester (1 x 10(-4) M), an inhibitor of NO synthesis, did not significantly affect progesterone and oestradiol secretion by rat ovaries; (iv) PGF2 alpha(1 x 10(-6) M) caused a fall in progesterone and oestradiol synthesis; (v) co-incubation with DETA/NO, significantly reversed the PGF2 alpha-induced decrease in progesterone concentrations from 184 +/- 29 to 388 +/- 60 ng/g (P < 0.01), but not that of oestradiol. It can be concluded that NO up-regulates progesterone secretion and down-regulates oestradiol secretion in rat ovaries, and NO can reverse PGF2 alpha-induced inhibition in ovarian progesterone secretion.     

Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium.

Besides being an antiprogestin, mifepristone (RU 486) was recently shown to antagonize oestrogen-dependent growth in the endometrium. To explore the molecular mechanisms for this phenomenon, we investigated whether or not the morphological effects of mifepristone are mediated by the progesterone receptor (PR) and whether mifepristone has disparate effects on the glandular epithelium and stroma. Six groups of hypogonadal, oestrogen-primed cynomolgus monkeys were treated for 2 weeks with: vehicle only (group I); mifepristone (group II); mifepristone plus progesterone at 0.2 mg/kg (group III), 1.0 mg/kg (group IV) or 5.0 mg/kg (group V); and progesterone only (5.0 mg/kg) (group VI). Histomorphological evaluation showed strikingly compacted stroma in the mifepristone-exposed endometria (group II), which was partially reversible by additional progesterone treatment (groups III-V). Glandular proliferation (pseudostratification, glandular mitoses) in mifepristone-treated monkeys was not significantly different from that in vehicle (oestradiol)-treated monkeys, but was inhibited by progesterone-only treatment. Cells containing vacuoles were scarce in the mifepristone-exposed endometrium, but detected frequently in progesterone-exposed endometria, indicating the strong antisecretory effect of mifepristone on glands. We conclude that oestrogen-dependent oedema in the stroma is antagonized by mifepristone. The reversal of this effect by progesterone suggests a PR-mediated mechanism. In glands, mifepristone is antiprogestogenic, but not antioestrogenic. Thus, stromal cells may be the target of antiprogestin-induced inhibition of oedema and endometrial growth.     

Changes in circulating concentrations of inhibins A and pro-alpha C during first trimester medical termination of pregnancy

BACKGROUND: Both inhibin A and inhibin pro-alpha C are detectable in the circulation in increasing amounts during establishment of pregnancy. However, their origins and functions remain to be elucidated. We have studied levels of inhibin A and inhibin pro-alpha C in serum samples collected at various stages during medical termination of pregnancy with consecutive use of mifepristone and misoprostol. METHODS: Samples were collected from three groups of patients at different weeks of gestation (group A: 6-7 weeks, n = 6; group B: 7-8 weeks, n = 6; group C: 8-9 weeks, n = 6) at the time of administration of oral mifepristone, 48 h later just before administration of vaginal misoprostol and again soon after expulsion of the products of conception. Plasma concentrations of inhibin A and pro-alpha C were assayed using specific and sensitive enzyme-linked immunosorbent assays. Results were correlated with concentrations of hCG and progesterone. RESULTS: We observed a significant fall in plasma concentration of inhibin pro-alpha C following administration of mifepristone, which continued after administration of misoprostol. In contrast mifepristone had no effect on plasma levels of inhibin A, which fell steeply only after administration of misoprostol. CONCLUSIONS: These results suggest dissociation between major sources of inhibin A and inhibin pro-alpha C in early pregnancy. Treatment with mifepristone, a competitive antagonist of the progesterone receptor, resulted in a significant and rapid fall in concentrations of inhibin pro-alpha C, identifying a link between production of pro-alpha C and luteal steroidogenesis. In contrast, concentrations of inhibin A did not fall after mifepristone, identifying a predominantly feto-placental origin in early human pregnancy.     

Endocrinology: The effect of nafarelin on human plasma adrenocorticotrophic hormone and cortisol concentrations

This study assessed the effects on plasma adrenocorticotrophichormone (ACTH) and cortisol concentrations of 3 months' treatmentwith intranasal nafarelin 200 µg b.d. in 11 women (aged26–43 years) for the treatment of endometriosis (n = 9),fibroids (n = 1) and pre-menstrual syndrome (n = 1). Serialblood samples were taken over 5 h, before and after nafarelinadministration on the first day of treatment, and after 1 and3 months' treatment. Control samples were taken before and afterintranasal placebo administration on the day before nafarelinwas commenced. The area under the curve (AUC) for mean ACTHconcentrations at each time point from 0 to 240 min was calculated.There were no statistically significant changes in total secretionof either ACTH or cortisol. There was a transient rise in ACTH30–60 min after nafarelin administration on the firstday of treatment in seven out of 11 women. The rise did notexceed the normal range. Seven women with ovarian suppression(oestradiol concentration < 175 pmol/l by day 28) had consistentlylower mean ACTH concentrations at all time points than the fourremaining women who had oestradiol concentrations 222–880pmol/l by day 28. Cortisol concentrations were unaffected bynafarelin. We conclude from the results of this study that 3months' treatment with nafarelin has no effects on adrenal function,as assessed by ACTH and cortisol concentrations.     

Effects of mifepristone on proliferation and apoptosis of human endometrium in new users of medroxyprogesterone acetate

BACKGROUND: Mifepristone has been demonstrated to decrease breakthrough bleeding (BTB) in users of progestin-only contraceptives. METHODS: Endometrial biopsies were collected from 50 normal cycling women who were new users of depot medroxyprogesterone acetate (DMPA) randomized to receive either mifepristone or placebo before, during and after treatment. Proliferation, apoptosis and sex steroid receptors were evaluated by either immunohistochemistry or TUNEL assay. RESULTS: Administration of mifepristone to DMPA-exposed endometrium for 1 week significantly increased endometrial expression of Ki-67 (MKI67), estrogen receptor (ER)alpha and progesterone receptors A and B (PRAB) and decreased the number of TUNEL-positive and caspase-3 (CASP3)-active cells in the endometrial stroma. However, after 10 weeks of mifepristone treatment, no significant difference in proliferation, apoptosis and the expression of ERalpha or PRAB could be detected between the endometrium treated with DMPA alone and endometrium treated with mifepristone and DMPA. CONCLUSIONS: Administration of mifepristone to DMPA users significantly increases endometrial proliferation and decreases endometrial stromal apoptosis in the short term. Prolonged exposure to mifepristone does not counteract the inhibitory effects of progestin therapy on endometrial proliferation. Estrogen and progesterone receptors may play an important role in these effects.     

The effect of progesterone upon first trimester trophoblastic cell differentiation and human chorionic gonadotrophin secretion.

The effect of progesterone (P) upon first trimester placental secretion of human chorionic gonadotrophin (HCG) and cellular differentiation was studied using both static and kinetic methods. At 1 microM, P inhibited spontaneous episodic secretion of HCG when given in short pulses (1-4 min) to placental explants in superfusion. Both HCG pulse frequency and amplitude were reduced. At 0.1-0.01 microM P concentrations, the effect of HCG secretion was milder. P also blocked the maximally effective concentration 100 pM of gonadotrophin releasing hormone (GnRH) analogue, a known HCG stimulant, when given together with it for 1 min. This inhibitory effect lasted for 1 h after P administration. Progesterone at 1 microM, added daily for 1 week blocked HCG secretion by isolated trophoblastic cells in static culture. This inhibitory effect lasted until the fifth day. No effect on differentiation and long-term viability was noticed in P-treated cells. Incubation with 0.1-1.0 microM P did not affect HCG secretion by explants after 24 h. In contrast, the effect of 1 microM cortisol or 1 nM oestradiol was stimulatory. In conclusion, P exerts both a rapid and delayed inhibitory effect upon HCG secretion and production. It may do so by counteracting the stimulatory effect of endogenous GnRH on gonadotrophin secretion by the placenta.     

The kinetics of serum hCG and progesterone in response to oral and vaginal administration of misoprostol during medical termination of early pregnancy

BACKGROUND: Misoprostol is widely used in combination with mifepristone for medical termination of pregnancy. We studied the endocrine parameters of trophoblast function during medical termination of early pregnancy using mifepristone in combination with oral or vaginal misoprostol. The effect of prolonged misoprostol administration was also examined. METHODS: Thirty-four women, requesting termination of pregnancy and with 相似文献   

Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland

We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[¹²⁵I] iodomelatonin binding ( K _d, 75.7 ± 6.9 p m ; B _max, 2.6 ± 0.4 fmol (mg protein)⁻¹), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro . Melatonin also inhibited ACTH-induced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light–dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.     

Oestradiol plus progesterone treatment increases serum leptin concentrations in normal women

BACKGROUND: Previous studies have alluded to a role for both oestradiol and progesterone in the secretion of leptin from fat cells in the human, although direct evidence has yet to be obtained. The study aim was to assess serum leptin concentrations in normally cycling women receiving exogenous oestradiol and progesterone. METHODS: Normally cycling women were investigated in an untreated spontaneous cycle (control, n = 10), a cycle treated with oestradiol (oestradiol cycle, n = 10) and a cycle treated with oestradiol plus progesterone (oestradiol+progesterone cycle, n = 6). Oestradiol was given to the women through skin patches on cycle days 2, 3 and 4, and progesterone intravaginally on cycle days 3, 4 and 5. Serum concentrations of leptin, oestradiol, progesterone, FSH and LH were measured in daily blood samples. RESULTS: During the treatment, serum oestradiol and progesterone concentrations increased significantly. In the oestradiol cycles, leptin concentrations were not affected by treatment and did not differ from those in controls. In the oestradiol+progesterone cycles, leptin concentrations (mean +/- SEM) increased in all women from cycle day 3 (8.6 +/- 1.1 ng/ml) to days 5 (12.2 +/- 1.8 ng/ml, P < 0.01) and 6 (11.9 +/- 2.0, P < 0.05), and were at these points significantly higher than in the control cycles (P < 0.05). The mean percentage increase from day 3 to the peak concentration on days 5 or 6 was 62.6 +/- 6.8%. Leptin concentrations returned to the pretreatment value on day 7, together with the concentrations of oestradiol and progesterone. In the oestradiol+progesterone cycles, leptin concentrations correlated significantly with oestradiol and progesterone concentrations, but not with FSH and LH concentrations. CONCLUSIONS: These results show, for the first time, that leptin secretion can be stimulated in women by the administration of oestradiol plus progesterone. This may explain the increased concentrations of leptin during the luteal phase of the normal menstrual cycle.     

Human ovarian steroid secretion in vivo: effects of GnRH agonist versus antagonist (cetrorelix).

BACKGROUND: In order to investigate whether gonadotrophin-releasing hormone (GnRH) antagonists exert a significant effect on steroid secretion in vivo compared with GnRH agonists, concentrations of sex steroid hormones (oestradiol, progesterone and testosterone) were studied in follicular fluid from women undergoing ovarian stimulation and treated with either GnRH agonist or antagonist. In addition, the correlation between follicular fluid steroid hormone concentrations and variables of follicular and oocyte development was evaluated. METHODS: Microparticle enzyme immunoassay and radioimmunoassays were used. RESULTS: The mean (SEM) follicular fluid oestradiol concentration was significantly lower in patients treated with GnRH antagonist than in those treated with GnRH agonist (542.0 +/- 76.9 versus 873.0 +/- 105.1 pg/ml, P = 0.02), which correlates with the mean serum oestradiol concentrations found in these two groups. No significant differences were found between groups in follicular fluid progesterone concentrations. Women undergoing GnRH antagonist treatment showed similar concentrations of follicular fluid testosterone compared with GnRH agonist-treated women (14.8 +/- 1.1 versus 13.3 +/- 2.7 ng/ml). The oestradiol:testosterone ratio was markedly reduced in women treated with GnRH antagonist (49.1 +/- 2.3 versus 60.1 +/- 4.4, P = 0.04). In contrast, no differences were found either in the progesterone:testosterone ratio, or in the oestradiol:progesterone ratio. CONCLUSIONS: GnRH antagonist therapy in women undergoing ovarian stimulation had a significant effect on ovarian follicular steroidogenesis.     

Vaginal absorption of oestradiol and progesterone

The vaginal absorption of micronized oestradiol/progesterone from a hydrophilic matrix system was investigated before and after 10 days of treatment in 7 post-menopausal women with an average age of 56.1 yr.

Oestradiol and progesterone levels were measured on days 1 and 11 before administration and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h afterwards by radioimmunoassay.

Peak values were seen 6–12 h after administration. This finding differs from those of other investigations. Sex hormone binding globulin (SHBG) and androgen concentrations were unchanged after 10 days of treatment.     

Endocrinology: Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women

Mifepristone interrupts folliculogenesis in women but the mechanismis not clear. Previous studies have investigated the effectof this compound on gonadotrophin secretion and have providedconflicting results. To study further the effect of mifepristoneon basal and gonadotrophin-releasing hormone (GnRH)-inducedgonadotrophin secretion, 12 normally ovulating women were investigatedduring two consecutive menstrual cycles, comprising an untreatedcycle (control) and a cycle treated with mifepristone. All womenwere treated with mifepristone on days 2–8 at the doseof 100 mg (group 1, eight women) or 10 mg per day (group 2,six women). Two women were treated with both regimens in twodifferent cycles. On day 8 of both cycles, the women receivedtwo GnRH pulses of 10 µg each 2 h apart. Blood samplesin relation to the first GnRH pulse were taken at –15,0, 30, 60, 120, 150, 180 and 240 min. In group 1, the increasein luteinizing hormone (LH) in response to GnRH was significantlyattenuated from 30 to 180 min, while the increase in folliclestimulating hormone (FSH) was attenuated only in response tothe second GnRH pulse. No significant decrease in LH and FSHresponse to GnRH was seen during treatment with the 10 mg dose(group 2). In group 1, serum oestradiol and inhibin-A concentrationsafter day 8 were lower than in the control cycles and the LHpeak was postponed by 7 days on average. Basal LH values increasedsignificantly on day 8 in both groups, while FSH values didnot change significantly compared with the control cycles. Asignificant increase in serum progesterone and cortisol valuesoccurred during the treatment only in group 1. Mid-luteal valuesof inhibin-A were significantly lower in cycles treated with100 mg mifepristone than in the control cycles. We concludethat the disruption of folliculogenesis by mifepristone cannotbe explained by a decrease in basal FSH concentrations duringthe critical period of follicle recruitment and selection. Itis possible that mifepristone exerts its effect at the levelof the ovary. It is also suggested that progesterone duringthe follicular phase of the cycle may participate in the controlof the self-priming action of GnRH on the pituitary.     

The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in-vitro fertilization patients.

The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer. One hundred and twenty-three follicular fluids were sampled. The mean follicular fluid levels (+/- SD) were 2.30 +/- 0.80 fmol for IL-2, 458.2 +/- 236.0 units/ml for sIL-2R, 28.5 +/- 58.1 ng/ml for oestradiol, 2360.5 +/- 2846 ng/ml for progesterone and 7.22 +/- 7.08 ng/ml for testosterone. There was a significant (P less than 0.01) correlation between IL-2 and testosterone levels. No correlation was found between the lymphokines and serum oestradiol, follicular fluid progesterone, oocyte fertilization, embryo quality and pregnancy. It may be concluded that significant concentrations of IL-2 and sIL-2R exist in follicular fluid. Wide variations in follicular IL-2 and sIL-2R concentrations of different follicles were found in the same patients.     

Andrology: Failure of oestrogen induced luteinizing hormone surge in women treated with mifepristone (RU 486) every day for 30 days

It has been demonstrated previously that administration of theantiprogestin mifepristone (RU 486; 1–5 mg daily) inhibitsor delays both the pre-ovulatory luteinizing hormone (LH) surgeand ovulation. To investigate this mechanism, dynamic testsof pituitary ovarian function were performed in six healthywomen before and during the administration of mifepristone (2mg daily for 30 days). On day 9 of the control and treatmentcycles, samples of blood were collected every 15 min over 12h for measurement of LH concentration. After 10 h, the responsivenessof the pituitary was tested by the i.v. injection of 10 µgof gonadotrophin-releasing hormone (GnRH). On day 10 of thecontrol and treatment cycles, two patches releasing 200 µg/dayof oestradiol were applied to skin on the abdomen for 3 days.Blood was collected at 24, 48, 59, 72, 81 and 96 h after applicationof the oestrogen patches for the measurement of gonadotrophinand ovarian hormone concentrations. Follicular development continuedin all women during their treatment with mifepristone, and ovulationwas suppressed (four women) or delayed (two women). There wasno significant difference in the basal concentration of LH betweenthe control and treatment cycles (mean ± SE; 5.5 ±0.4 versus 7.7 ± 0.4 IU/l respectively), or in the frequency(interpulse interval, 101 ± 12 versus 105 ± 13min respectively) and the amplitude (2.1 ± 0.4 versus2.6 ± 0.4 IU/l respectively) of LH pulses. The responseto GnRH was similar. On day 10, the basal concentrations ofLH, follicle-stimulating hormone (FSH), prolactin, oestradioland progesterone and the diameter of the dominant follicle (15.7± 1.8 versus 13.3 ± 1.9 mm) were similar duringcontrol and treatment cycles. In control cycles, there weresignificant increases in the concentrations of LH and FSH within72 h of application of the oestrogen patches. During treatmentcycles, concentrations of FSH and LH remained low, and weresignificantly lower than the values observed during controlcycles (P < 0.006). We conclude that the antiprogestin mifepristonedisrupts ovulation by inhibiting the positive feedback effectof oestrogens and, hence, prevents or delays the generationof a pre-ovulatory LH surge.