宫颈粘液过氧化物酶在月经周期中的变化规律

本文对29例月经周期正常妇女的宫颈粘液过氧化物酶进行了30个周期的研究。在月经周期不同时间测定宫颈粘液过氧化物酶(CMPx)活性及血清促黄体生成素(LH)、雌二醇(E_2)和孕酮(P)。结果表明:在排卵前三天酶活性明显下降,至排卵后一天开始上升。卵泡期,酶活性与E_2呈负相关(r=-0.67);黄体期,酶活性与P呈正相关(r=0.79)。本研究提示:1.CMPx在排卵周期具有特定的变化规律,其变化受体内激素水平影响,可作为预告排卵的指标。2.如简化测定方法,可为自然避孕提供新途径。     

Synthesis of gonadotrophins and its regulation in the pituitary gland

Regulation of the synthesis of pituitary gonadotrophins LH andFSH has been studied in the rat using either cell-free translationof pituitary mRNAs, or hybridization techniques with syntheticoligodeoxynucleotides or cloned complementary DNAs. Gonadectomygreatly increases and supplementing gonadectomized rats withgonadal steroids diminishes the rate of synthesis of the gonadotrophinsubunits. Hybridization experiments suggest that gonadal steroidsregulate the expression of the genes coding for pituitary gonadotrophinsubunit precursors. Using the incorporation of labelled methionineby pituitary cells in culture, followed by specific immunoprecipitationof LH-related subunits and SDS-poly-acrylamide gel analysisof immunoprecipitated peptides, there was evidence that gonadotrophinreleasing hormone (GnRH) significantly enhances the radioactivityincorporated into both - and LH-subunits. This effect is specific,it is not a secondary effect due to the release of LH. A cyclicAMP (cAMP) analogue, 8-Br-cAMP, as well as forskolin and choleragen,which are cAMP generators and a diacylglycerol analogue, tetradecanoylphorbolacetate (TPA), mimic the stimulatory action of GnRH on the synthesisof the polypeptide chains of LH. However, no evidence has beenobtained that either cAMP or diacylglycerols mediate this GnRHeffect. These results suggest that the synthesis of pituitarygonadotrophins is under a double control of gonadal steroidsand GnRH which exert opposite effects, inhibitory for steroidsand stimulatory for GnRH. The negative control by steroids occursat the genomic level, while the positive effect of GnRH proceedsvia different mechanisms which remain to be elucidated.     

Inhibitory effect of plasma obtained from hypophysectomized and control women on the assay of bioactive luteinizing hormone

The purpose of this study was to determine the effect of components of female plasma on the value of bioactive luteinizing hormone (LH), especially in the presence of low immunological LH value. Using both an immunoradiometric assay (IRMA) and rat Leydig cell bioassay, immunoreactive (I) and bioactive (B) LH were assessed in plasma collected from women during a gonadotrophin releasing hormone (GnRH) test performed on day 7 of a spontaneous cycle. Two modes of response to an acute administration of GnRH were defined: normal production of gonadotrophins (group I) and excessive secretion (group II) associated with a significant difference in the B/I-LH ratio between the two groups. The B/I-LH ratio did not vary with sampling time during the test in either group. The addition of LH-free plasma collected from hypophysectomized women caused a 30% decrease in testosterone production compared to control values (in the presence or absence of hLH standard). A partial restoration of testosterone production was observed if plasma was first treated with PEG 12%. The inhibitory factor(s) was also present in plasma from ovulatory women, even after treatment by an antibody against the entire LH molecule. The effect of normal (A) or low I-LH plasma (B) on testosterone production varied strongly according to the plasma volume added to the bioassay, as well as to plasma treatments. Diethylether treatment caused a 50% decrease in testosterone secretion for plasma B (but not for A) whereas a diminution of the steroidogenesis is observed after a PEG treatment of plasma A (but not for B), suggesting that different inhibitory factors are present in plasmas A and B. Therefore the LH bioactivity measured in the rat Leydig cell assay, in terms of testosterone output, seems to represent a balance between the LH molecule and the presence of inhibitory factors in the plasma.     

Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age

BACKGROUND: Fetal growth restraint has been associated with FSH hypersecretion in early infancy and in early post-menarche, and with reduced uterine and ovarian size in adolescence. It is unknown whether these reproductive anomalies persist, respectively, into late infancy and into the reproductive age range. METHODS: We report follow-up findings in two age groups of girls. A cohort of infants [n=26; n=10 born appropriate-for-gestational-age (AGA) and n=16 born small-for-gestational-age (SGA)], who had been studied at the age of approximately 4 months, was assessed again at the age of 12 months. A cohort of teenagers (n=28), who had been studied at the age of approximately 14 years, was assessed again at the age of approximately 18 years; this group was complemented by a transversal cohort of similar age (n=19) for a total of 47 young women (n=27 AGA; n=20 SGA). In infants, only serum FSH was measured; adolescents underwent endocrine-metabolic screening, ultrasound assessment of uterine-ovarian size, and evaluation of body composition by dual X-ray absorptiometry. RESULTS: Serum FSH levels were higher in SGA than AGA infant girls at 4 and 12 months, and higher in SGA than AGA adolescents at 14 and 18 years (all P<0.01). Longitudinal ultrasound assessments disclosed a late-adolescent increment of uterine size that was less obvious in SGA than AGA girls. In contrast, ovarian volume remained stable in both subgroups. Compilation of longitudinal and transversal results at 18 years of age corroborated the persistent reduction in the uterine size of SGA girls (by approximately 20%; P<0.005) and in their ovarian volume (by approximately 40%; P<0.0001); moreover, SGA girls displayed not only a persistent elevation of FSH (by approximately 50%; P<0.001), but also a rise of LH and fasting insulin, as well as an excess of abdominal fat (all P<0.01). CONCLUSIONS: The gynaecology of young women born SGA was found to be characterized by hypergonadotrophinaemia and by a reduced uterine and ovarian size.     

Adrenaline turnover rates in the medial preoptic area and mediobasal hypothalamus in relation to the release of luteinizing hormone in female rats

The turnover rates of adrenaline in the medial preoptic area and mediobasal hypothalamus, areas which, respectively, include the cell bodies and terminals of luteinizing hormone-releasing hormone neurons, have been measured in female rats on pro-oestrus, the day of the preovulatory surge of luteinizing hormone, and on dioestrus, the preceding day. A rise in the rate of turnover was found in the medial preoptic area coinciding with the surge of luteinizing hormone in the late afternoon of pro-oestrus; the rate of turnover at this time was higher than at the same time on dioestrus. No changes in turnover rate were found in the mediobasal hypothalamus within either of these days.The results indicate that the adrenaline-containing projections to the preoptic area may be actively involved in the production of the spontaneous preovulatory surge of luteinizing hormone in rats.     

Feasibility of administering mifepristone as a once a month contraceptive pill

Many women find the idea of a once-a-month contraceptive pill an attractive concept. Mifepristone has been shown to be effective as a contraceptive if administered in the early luteal phase. We tested the contraceptive efficacy of 200 mg of mifepristone on day luteinizing hormone (LH) + 2 in a group of 32 women who used a fertility monitor to identify the LH surge. We also recruited a control group, comprising 20 women who were trying to conceive. In this group, 12 women conceived during a total of 50 control cycles (probability of pregnancy 0.25-0.32). Women in the treatment group contributed to a total of 178 cycles and there were two pregnancies (probability of pregnancy 0.01). An LH surge was not detected in 34 cycles (19.1%). In 20 cycles (11.2%) this was due to imperfect use while 14 were monitor method failures (7.9%). Treatment with mifepristone in the early luteal phase did not disrupt the cycle length but women reported slight vaginal bleeding in 15% of the cycles. The combination of a home-use fertility monitor with once-a-month administration of mifepristone (especially if mifepristone is administered at the early luteal phase) is an acceptable contraceptive option with minimal side effects. Unfortunately, it is difficult to envisage how an easier way of defining the correct timing, which required less compliance, could be devised.     

Effects of aging on luteinizing hormone release in different physiological states of the female golden hamster

Effects of aging on estrous cycles and LH release in response to luteinizing hormone releasing hormone (LHRH), castration, and estradiol benzoate were studied in the female golden hamster (Mesocricetus auratus). About 80% to 90% of female golden hamsters still cycled regularly when reaching 19–22 months of age. However, some animals showed age-induced irregularity of the estrous cycle which included an interruption of complete absence of estrous vaginal discharge. Young female hamsters (3–5 months) had significantly (p<0.01) higher basal LH concentration than old animals (19–22 months) in the morning of each stage of estrous cycle. LHRH elicited about 20–30 fold increase in serum LH concentrations in both young and old hamsters. No significant difference in LH release was observed between young and old hamsters in response to LHRH. In acyclic hamsters, the peak of LH release in response to LHRH was delayed. LHRH-induced LH release was greater in the morning of proestrus than during diestrus in both young and old hamsters. LH increase was significantly greater in the young than in old hamsters on the 13th and 15th day after castration. However, positive feedback stimulation of LH release by estradiol benzoate was the same in both young and old hamsters. These results indicate that in the female hamster, LH response to acute stimuli such as LHRH and estrogens is the same in the young as in the old animal and that circulating basal LH concentration may decrease or its degradation or clearance may increase during the aging process in female golden hamsters. Irregularity of estrous cycles in aging hamsters may be related to delayed responsiveness of pituitary LH to LHRH stimulation.     

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.     

Effects of manipulating catecholamines on the incidence of the preovulatory surge of of luteinizing hormone and ovulation in the rat: evidence for a necessary involvement of hypothalamic adrenaline in the normal or 'midnight' surge

The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Induction of ovulation after gnRH antagonists

The gonadotrophin-releasing hormone (GnRH) antagonist binds competitively to the receptors and thereby prevents endogenous GnRH from exerting its stimulatory effect on the pituitary cells. This causes suppression of gonadotrophin secretion which occurs immediately after administration of the antagonist. When using GnRH antagonist in controlled ovarian stimulation, ovulation or maturation of the oocyte can, therefore, be induced by a variety of drugs, e.g. native GnRH, recombinant LH or short-acting GnRH agonists. Short-acting GnRH agonists were recommended for triggering ovulation in cases with a high risk of developing ovarian hyperstimulation syndrome (OHSS). Since it is evident that GnRH is required to initiate the LH surge and the oestradiol rise, a single administration of GnRH antagonist during the late follicular phase delays the LH surge. Studies showed that a single s.c. administration of 3 or 5 mg of Cetrorelix in the late follicular stage was sufficient to prevent the LH surge for 617 days. This phenomenon can be used in high responder patients who are prone to OHSS. The question whether this delay has any effect on oocyte quality and maturation still remains unanswered. Overall, there are four uses for GnRH antagonist: (i) using short-acting GnRH agonists for triggering ovulation in cases in which the GnRH antagonist is part of the protocol for ovarian stimulation. Recombinant LH and native LHRH could also be used as triggers of LH surge; (ii) delaying the LH surge in cases prone to OHSS by treatment with GnRH antagonist; (iii) to administer GnRH antagonist during the luteal phase to decrease the activity of corpora lutea; (iv) in polycystic ovarian disease with elevated LH the LH/FSH ratio can be corrected with the injection of GnRH antagonist prior to and during ovarian stimulation.