Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy

Objective.?To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET).

Methods.?Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P?<?0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET.

Results.?There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET.

Conclusions.?Maternal IGF-2 has a significant positive correlation with PET.     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿生长发育的关系

目的:探讨胰岛素样生长因子1（IGF-1）及胰岛素样生长因子结合蛋白3（IGFBP-3）与胎儿生长发育的关系。方法:应用酶联免疫吸附试验（LISA）测定26例正常妊娠（正常组）,42例妊娠期糖尿病（GDM组）,20例胎儿宫内发育迟缓（IUGR组）孕妇足月剖宫产分娩时,母血与脐血中IGF-1及IGFBP-3的水平,同时记录3组孕妇的新生儿出生体重。结果:（1）母血IGF-1及IGFBP-3的水平正常组分别为18 6.81μg/L、22.82μg/L,GDM组为283.35μg/L、28.29μg/L,IUGR组为220.64μg/L、25.23μg/L,3组间 IGF-IN IGFBP.3水平差异均无显著性（P>0.05）;（2）脐血IGF-1及IGFBP-3的水平正常组分别为62.54μg/L、8.56μg/L,GDM组分别为83.74μg/L、10.21μg/L,IUGR组为37.94μg/L、7.82μg/L,分别进行3组间两两比较,3组IGF-1及IGFBP-3的差异均有显著性（P<0.01）;（3）新生儿平均出生体重正常组为3.22±0.32kg,GDM组为3.76±0.43kg,IUGR组为2.41±0.17kg,3组间两两比较,差异均有显著性（P<0.01）;（4）3组脐血IGF-1及IGFBP-3水平与新生儿出生体重均有显著性正相关（P<0.01）;（5）3组母血及脐血的IGF-1与IGFBP-3均呈显著性正相关（P<0.01）。结论:来自胎儿循环的IGF-1、IGFBP-3对胎儿的生长发育有重要的调节作用,可能参与巨大儿及IUGR的病     

The effects of somatostatin in the polycystic ovary syndrome.

Eighteen obese women (body mass index 30 +/- 6.1 kg/m2) with hyperinsulinaemia and with the polycystic ovary syndrome took octreotide at the dose of 100 mug s.c. The effect of the drug was assessed on plasma levels of gonadotropins luteinising hormone (LH), follicle stimulating hormone (FSH), of insulin, insulin-like growth factor-1 (IGF-1), androstenedione, testosterone, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG) and insulin-like growth factor-binding protein-3 (IGFBP-3). Octreotide significantly reduced LH (31.8%), insulin (52%), IGF-1 (14%), androstenedione (22.6%) and testosterone (20%) and increased IGFBP-3 (25%).     

Is there evidence for preferential delivery of ovarian estradiol to the endometrium?

Objective: To determine the direction of delivery of E₂ in the female pelvis by assessing the ratio of endometrial to serum E₂ in women whose ovaries were stimulated to produce E₂ with women who received exogenous E₂.

Design: Prospective comparative study.

Setting: University-based ART program.

Patient(s): Oocyte donors and recipients of donor oocytes.

Intervention(s): Micronized E₂ administered by the oral or vaginal route and oocyte donation.

Main Outcome Measure(s): Serum and endometrial levels of E₂.

Result(s): Serum E₂ levels were significantly higher in women who underwent controlled ovarian hyperstimulation (COH) and women receiving exogenous E₂ by the vaginal route than in those who received oral E₂. Levels of E₂ in endometrial tissue were similar in women who underwent COH and those receiving oral E₂. Endometrial E₂ levels in women who underwent vaginal administration were significantly higher than those in the oral E₂ or COH groups. The ratio of endometrial to serum E₂ was highest in women who underwent vaginal E₂ and lowest in those undergoing COH.

Conclusion(s): Vaginal administration of micronized E₂ results in preferential absorption of E₂ into the endometrium, consistent with a “uterine first pass” effect. Since endogenous E₂ produced the smallest ratio of E₂ between the endometrium and serum, E₂ produced by the ovaries is not preferentially delivered to the uterus.     

IGF-1、IGF-2、IGFBP-3与非糖尿病孕妇巨大儿发生的相关性研究

目的探讨胰岛素样生长因子1、2（IGF-1、IGF-2）、胰岛素样生长因子结合蛋白3（IGFBP-3）与非糖尿病孕妇巨大儿发生的关联性。方法选择2010年1月至2011年5月于上海市浦东新区人民医院产前检查并分娩的初产妇,孕期纵向观察,抽取妊娠中期（26～28周）和妊娠足月（38～41周）的母血及孕妇分娩时新生儿出生体重≥4000g30例（巨大儿组）、2500～3500g30例（正常组）的脐血,应用放射免疫法检测IGF-1、IGF-2、IGFBP-3的水平,并进行对比分析。结果①两组孕妇妊娠足月IGF-1水平均高于妊娠中期,差异有高度统计学意义（分别为P〈0.0001、P〈0.001）,但妊娠中期和足月时,巨大儿组与正常组二组间比较差异均无统计学意义（P〉0.05）。巨大儿组脐血IGF-1水平高于正常组,差异有高度统计学意义（P〈0.0001）;②孕妇血清IGF-2水平巨大儿组与正常组比较差异无统计学意义（P〉0.05）;③孕妇妊娠中期、妊娠足月血清IG-FBP-3水平巨大儿组明显高于正常组,差异有高度统计学意义（分别为P〈0.001、P〈0.01）;④母血IGFBP-3水平、脐血IGF-1水平与新生儿出生体重正相关。结论 IGF-1参与了胎儿生长发育的调节;胎儿自身循环中的IGF-1与新生儿出生体重有关;非糖尿病孕妇血清IGFBP-3水平与巨大儿形成有关。     

Serum levels of insulin, IGF-1, and IGFBP-1 in pre-eclampsia and eclampsia.

OBJECTIVES: To investigate whether the serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women with mild pre-eclampsia, severe pre-eclampsia, and eclampsia. METHODS: In this prospective study, we investigated 20 mild pre-eclamptic, 20 severe pre-eclamptic, and 20 eclamptic patients in the third trimester. The control group consisted of 20 healthy pregnant women. Serum levels of insulin, IGF-1, and IGFBP-1 were measured. RESULTS: In patients with eclampsia, serum levels of IGF-1 were lower, and IGFBP-1 were higher, respectively, than control and other study groups (P<0.001) The values of IGF-1 in mild pre-eclampsia and severe pre-eclampsia were lower compared with control groups (both P<0.01), but there were no differences between mild and severe pre-eclampsia. The serum levels of IGFBP-1 in severe pre-eclampsia were higher compared with control groups (P<0.01), but there was no statistical difference between mild pre-eclampsia and other groups. CONCLUSIONS: IGF-1 was lower, and IGFBP-1 was higher in pre-eclamptic and eclamptic patients than controls, these alterations were related to the severity of pre-eclampsia.     

Regulation of insulin-like growth factor binding protein secretion by human granulosa luteal cells in a polycystic ovary-like environment

OBJECTIVE: To determine the effect of androstenedione (A), insulin, and LH on secretion of insulin-like growth factor binding proteins (IGFBPs) from human granulosa luteal cells. DESIGN: Human granulosa cells were cultured for a total of 4 days in serum-free medium containing A (10(-6) mol/L), with or without insulin (100 microU/mL-800 microU/mL), LH (1 microU/mL-10 microg/L), and A (10(-5) mol/L). SETTING: Granulosa cells were obtained from IVF procedures. PATIENT(S): Women undergoing IVF for tubal disease. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Immunoassay and autoradiographs of Western ligand blotting detected IGFBP accumulations in the medium. RESULT(S): Cultured granulosa cells secreted IGFBP-1 through IGFBP-4. Insulin (100 microU/mL-800 microU/mL), LH (1 microg/L-10 microg/L), and A (10(-5) mol/L) caused a significant decrease in IGFBP-1 accumulation in the medium both alone and when added in combination. The release of IGFBP-2 and IGFBP-4 was significantly stimulated by insulin, whereas LH had no effect. Elevated levels of androgen (10(-5) mol/L) significantly stimulated the secretion of IGFBP-2, whereas the release of IGFBP-4 was reduced. CONCLUSION(S): These results demonstrate that androgen and insulin are important regulators of IGFBP release and that elevated levels of the two hormones may contribute to the altered IGFBP profile found in PCOS follicles, compared with the case of estrogen-dominant follicles.     

Effects of the route of estrogen administration and exercise on hormonal levels in postmenopausal women

Objective: To examine the effects of exercise on serum estrogens, growth hormone, insulin, cortisol, lactate, and glucose levels in postmenopausal women receiving two routes of administration of estrogen replacement therapy (ERT).

Design: Prospective, randomized, crossover study.

Setting: The general clinical research center of an academic medical center.

Patient(s): Eleven active, postmenopausal women.

Intervention(s): The patients were screened with exercise stress testing, then oral micronized estradiol or transdermal estradiol was administered, followed by two 45-minute submaximal exercise tests. Dietary intake before the tests was standardized.

Main Outcome Measure(s): The study measured maximal heart rate and aerobic power ( ₂max), and serum levels of estradiol (E₂), estrone (E₁), cortisol, growth hormone (GH), insulin, glucose, and lactate.

Result(s): Growth hormone, cortisol, and insulin all changed significantly in response to the 45-minute exercise bouts, but no differences were observed between the oral micronized estradiol and transdermal estradiol responses. E₂ levels increased significantly during the transdermal estradiol 45-minute exercise bout; this change did not occur during the oral estradiol exercise bout. In the transdermal estradiol treatment group, the E₂ levels at +30 and +45 minutes of exercise were elevated compared to the post-exercise levels at −15, 0, and 30 minutes. E₁ was not significantly changed during the 45-minute exercise bouts in either group.

Conclusion(s): During exercise, serum E₂ levels rise significantly higher with transdermal but not oral routes of E₂ administration. However, the elevated levels are not prolonged and normalize by 30 minutes after exercise.     

Maternal zinc and cord blood zinc, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels in small-for-gestational-age newborns

PURPOSE: To determine the relationship between maternal serum zinc (Zn) levels and birth weight of the offspring and their correlation with cord blood Zn, insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels. METHOD: 22 term small-for-gestational-age (SGA) and 34 term appropriate-for-gestational-age (AGA) infants and their mothers were included. Maternal and cord blood Zn levels and cord blood IGF-1 and IGFBP-3 levels were measured. RESULTS: Eighteen percent of mothers had Zn deficiency (< 75 mcg/dl). No significant difference between IGF-1 and IGFBP-3 levels and birth weight of infants of the mothers with and without Zn deficiency was found. Maternal and neonatal Zn levels correlated (r = 0.38, p < 0.01). Mean IGF-1 and IGFBP-3 levels were significantly lower in the SGA group compared to the AGA group (42.3 +/- 16.8 ng/ml, 1.2 +/- 0.2 mcg/ml, and 62.4 +/- 22.7 ng/ml, 1.5 +/- 0.4 mcg/ml, p < 0.001). A correlation was found between birth weight, IGF-1 and IGFBP-3 levels, and weight gain of the mother during pregnancy (p < 0.01). CONCLUSIONS: Zn deficiency was not observed to be a risk factor for low birth weight. The significant difference between the SGA and AGA babies' IGF-1 and IGFBP-3 levels emphasizes function of the IGF system in intrauterine growth.     

A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome

Objective: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC).

Design: Subgroup analysis within a randomized, controlled, multicenter study.

Setting: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands.

Patient(s): Twenty-eight infertile patients with PCOS.

Intervention(s): Patients were randomly assigned to pulsatile IV GnRH (10–20 μg/90 min) after GnRH-a down-regulation or CC (50–150 mg; cycle days 3–7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E₂, LH, and FSH. Serum P and sonography confirmed ovulation.

Main Outcome Measure(s): Serum concentrations of E₂, LH, and FSH were assessed before treatment was started and after each ovarian sonography.

Result(s): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E₂, LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group.

Conclusion(s): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion.     

青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化

目的观察青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化。方法选取4周龄SPF级雌性SD大鼠10只,随机分为观察组和对照组各5只。观察组大鼠经尾静脉注射阿霉素6.5mg/kg制备肾病模型,对照组大鼠经尾静脉注射等量生理盐水。观察阿霉素注射后1、2、3、4周SD大鼠体质量、子宫湿重、头尾长、胫骨长度变化及测定24h尿蛋白;透射电镜下观察足细胞超微结构变化;放射免疫法分析血清雌二醇(E_2)、促黄体生成素(LH)、促卵泡生成素(FSH)、胰岛素样生长因子1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)的变化。结果阿霉素注射后4周青春早期SD雌性大鼠尿蛋白显著高于对照组,差异有统计学意义(P0.05)。青春期雌性SD大鼠在阿霉素注射后足细胞足突融合逐渐加剧,在阿霉素注射后4周雌性SD大鼠肾小球足细胞足突出现广泛融合。观察组体质量在阿霉素注射后2、3、4周减轻逐渐加剧,与对照组比较差异有统计学意义(P0.05)。观察组头尾长在阿霉素注射后4周较对照组明显减少,差异有统计学意义(P0.05)。观察组胫骨长度和子宫湿重在阿霉素注射后2、3、4周后与对照组比较无明显减少,差异无统计学意义(P0.05)。观察组血清LH、FSH、E_2、IGF-1和IGFBP-3在阿霉素注射后2、3、4周与对照组比较无明显改变,差异无统计学意义(P0.05)。结论青春早期雌性SD大鼠在阿霉素肾病模型过程中未出现明显的生长发育迟滞,血清生长相关激素和性激素分泌未出现明显降低。     

Young Low Responders Protected from Untoward Effects of Reduced Ovarian Response

Objective(s): To correlate fertilization and clinical pregnancy rates (PRs) in low responders with their E₂ levels (<500, 500–800, >800–1,000 pg/mL), age (20–30, 31–40, >40 years), number of follicles, and number of oocytes retrieved.

Design: A retrospective study.

Setting: The IVF unit of an academic hospital.

Patient(s): One hundred forty-three women who failed to attain E₂ levels of 1,000 pg/mL on the day of hCG administration.

Intervention(s): Controlled ovarian hyperstimulation, blood E₂ and progesterone measurements, ultrasonographic scanning of ovarian follicles, oocyte retrieval after hCG administration, and ET.

Main Outcome Measure: Clinical PR.

Result(s): Although E₂ levels, fertilization rates, age, and number of oocytes did not differ significantly between the three age groups, the PR achieved in the youngest group was approximately three times as high (19.3%) as that achieved in the two older groups.

Conclusion: Young low responders represent a unique subset in that their age protects them from the deleterious effects of poor ovarian response.     

The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation

Objective: To discuss the clinical therapeutic window for LH during the follicular phase.

Design: Review of selected papers that were retrieved through a Medline search and a review of clinical trials, the results of which are in the process of publication.

Patient(s): Women undergoing infertility treatment.

Intervention(s): Recombinant human LH (r-hLH) was administered SC as a supplement to FSH during controlled ovarian hyperstimulation.

Main Outcome Measure(s): Follicular development, E₂ production, and endometrial thickness.

Result(s): Optimal follicular maturation is the result of both FSH and LH stimulation. In patients with hypogonadotropic hypogonadism, 75 IU of r-hLH and 150 IU of FSH per day resulted in more follicles and provided sufficient E₂ for optimal endometrial proliferation. Additional r-hLH (>250 IU/day), in patients with either hypogonadotropic hypogonadism or polycystic ovary disease, may precipitate a series of deleterious physiological actions leading to atresia of developing follicles. Adding r-hLH to FSH in women treated with GnRH agonist showed no benefits in terms of number of mature oocytes, fertilization, and cleavage. However, those who experience profound pituitary desensitization may benefit from adding LH to the stimulation protocol. No obvious clinical criteria have been established to define this group of patients.

Conclusion(s): A “threshold” and “ceiling” level for LH (therapeutic window) is proposed, below which E₂ production is not adequate and above which LH may be detrimental to follicular development.     

Immunohistochemical localization of insulin-like growth factor-binding protein-3 in eutopic and ectopic endometrial tissues

Objective: To evaluate the expression of insulin-like growth factor–binding protein-3 (IGFBP-3) in the eutopic endometrium and in endometriotic lesions.

Design: Retrospective immunohistochemical study.

Patient(s): Twenty-five normal women and 39 women with endometriosis.

Intervention(s): Endometrial and endometriotic tissue biopsies obtained at laparoscopy.

Main Outcome Measure(s): Expression of IGFBP-3 assessed by immunohistochemistry.

Result(s): In the endometrium, positive immunostaining of IGFBP-3 was observed both in the stroma and the epithelial glands. The intensity of staining in the glands during the secretory phase was significantly higher in women with endometriosis compared with controls (P=.018). An increased expression of IGFBP-3 over controls was found in stages I and II of the disease (P=.018), whereas in stages III and IV, the difference between controls and women with endometriosis was not significant (P=.300). In endometriotic tissues, a much-marked immunostaining of IGFBP-3 was noted in 90% of the glands and 67% of the stroma without apparent differences related to cycle phase.

Conclusion(s): These data show intense staining of IGFBP-3 in endometriosis lesions and increased expression of the protein in the endometrium of patients with endometriosis compared to controls. This marked expression of IGFBP-3 could be related to its previous finding in the peritoneal fluid and to its potential involvement in the pathophysiology of endometriosis.     

Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome

OBJECTIVE: To evaluate the effects of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: Women with PCOS attending as outpatients of the Endocrine Division, Hospital Durand, Buenos Aires. PATIENT(S): Twenty-four insulin-resistant women with PCOS. INTERVENTION(S): Hormonal evaluations and a standardized oral glucose tolerance test before and after a 3-month trial of 4 mg of rosiglitazone daily. MAIN OUTCOME MEASURE(S): Serum LH, FSH, T, IGF-1, IGFBP-1, IGFBP-3, leptin, 17alpha-hydroxyprogesterone, insulin, and glucose concentrations. The area under insulin curve (AUC-insulin), the HOMA index (insulin resistance), the QUICKI index (insulin sensitivity), and the beta-cell function were calculated. Body mass index (BMI) and the waist/hip ratio were evaluated. RESULT(S): A significant decrease was observed in serum fasting insulin, AUC insulin, HOMA index, beta-cell function, IGF-1, LH, and waist/hip ratio. The QUICKI index and IGFBP-1 increased significantly. Serum sex hormone-binding globulin, androgens, leptin, IGFBP-3, and BMI remained unchanged. Twenty-two of 23 females had their menses restored, and three patients became pregnant. One patient was excluded because she became pregnant at the second month. CONCLUSION(S): Associated with the decrease in LH, rosiglitazone improved insulin-resistance parameters and normalized the menstrual cycle, which suggests that this drug could improve the endocrine-reproductive condition in insulin-resistant women with PCOS.     

Maternal and fetal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3, and their relationship to fetal acidosis at delivery

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and in fetal cord blood at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, Illinois, USA), with p<0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking and in fetal blood by cord blood analysis at delivery. Cord pH was also recorded. RESULTS: There was no significant correlation between maternal IGF-1, IGF-2, or IGFBP-3 levels and fetal acidosis. However, a significant correlation does exist between cord IGF-1 levels and fetal acidosis. CONCLUSION: Fetal cord IGF-1 has a significant correlation with fetal acidosis at delivery.     

Raised serum levels of matrix metalloproteinase-9 in women with polycystic ovary syndrome and its association with insulin-like growth factor binding protein-1

Background.?It has been suggested in recent studies that matrix metalloproteinases (MMPs) may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS) through regulating ovarian tissue remodeling. In addition to degrading the extracellular matrix, MMPs exhibit the ability to cleave insulin-like growth factor binding protein-1 (IGFBP-1), the major regulator of insulin-like growth factor-I (IGF-I) in serum. The present study aimed to investigate the possible role of MMPs in the pathophysiology of PCOS.

Methods.?Serum levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), IGF-I and IGFBP-1 were measured in 42 patients with PCOS and 30 healthy women with regular menstruation, matched for age and body mass index. Correlation between IGFBP-1 and other parameters in the PCOS group was analyzed by Pearson's linear correlations.

Results.?Serum MMP-9 concentrations and MMP-9/TIMP-1 ratios were significantly higher in PCOS women than in controls. Serum levels of IGFBP-1 were markedly lower in the PCOS group. There was a negative correlation between serum IGFBP-1 and MMP-9 in women with PCOS.

Conclusion.?Our results raise the possibility that MMPs may be implicated in the pathophysiology of PCOS either by regulating ovarian tissue remodeling or indirectly by facilitating IGF-I bioavailability through proteolysis of IGFBP-1.     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白1表达与妊娠期高血压疾病发病的关系

目的探讨胰岛素样生长因子1(IGF-1)与胰岛素样生长因子结合蛋白1(IGFBP-1)在妊娠期高血压疾病发病中的作用。方法采用酶联免疫吸附法(ELISA)及免疫组化方法检测60例妊娠期高血压疾病患者(妊娠期高血压疾病组,其中妊娠期高血压20例、轻度子痫前期19例、重度子痫前期21例)及18例正常妊娠妇女(对照组)的血清及胎盘组织中IGF-1及IGFBP-1的水平,并分析妊娠期高血压疾病组患者血清中IGF-1水平与胎盘组织中IGFBP-1的相关性。结果(1)血清IGF-1水平:妊娠期高血压疾病组为(229±100)μg/L,明显低于对照组的(336±120)μg/L,两组比较,差异有统计学意义(P<0.01)。妊娠期高血压患者血清中IGF-1水平为(303±80)μg/L,轻度子痫前期患者为(233±77)μg/L,重度子痫前期患者为(155±73)μg/L。3者间比较,差异有统计学意义(P<0.05)。(2)胎盘组织中IGF-1阳性率:妊娠期高血压疾病组为48%(29/60),明显低于对照组的83%(15/18),两组比较,差异有统计学意义(P<0.01);轻、重度子痫前期患者明显低于对照组(P<0.05,P<0.01)。(3)血清中IGFBP-1水平:妊娠期高血压疾病组为(161±90)μg/L,明显高于对照组的(98±75)μg/L,两组比较,差异有统计学意义(P<0.01)。妊娠期高血压患者为(97±73)μg/L,轻度子痫前期患者为(157±69)μg/L,重度子痫前期患者为(225±81)μg/L。3者间比较,差异有统计学意义(P<0.05)。(4)胎盘组织中IGFBP-1阳性率:妊娠期高血压疾病组为77%(46/60),明显高于对照组的39%(5/18),两组比较,差异有统计学意义(P<0.01);轻、重度子痫前期患者明显高于对照组(P<0.05,P<0.01)。(5)相关性:妊娠期高血压疾病组患者血清及胎盘组织中IGF-1水平分别与相应部位的IGFBP-1水平均呈负相关(r=-0.269,P<0.05;r=-0.396,P<0.01)。血清中IGFBP-1水平与胎盘组织中IGFBP-1表达水平呈正相关(r=0.388,P<0.01)。结论孕妇血清及胎盘组织中IGF-1、IGFBP-1水平变化与妊娠期高血压疾病发病及病情发展有关。