Manuel Maliqueo

University of Gothenburg, Goeteborg, Västra Götaland, Sweden

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Publications (54)183.67 Total impact

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    ABSTRACT: Does polycystic ovary syndrome (PCOS) in women without pregnancy complications affect placental signal transducer and activator of transcription 3 (STAT3) and mechanistic target of rapamycin (mTOR) signaling? Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS. Women with PCOS have increased risk of poor pregnancy outcomes (e.g. restricted or accelerated fetal growth), indicating placental dysfunction. Placental STAT3 and mTOR pathways regulate placental function and indirectly affect fetal growth. In a case-control study, placental tissue and maternal blood were collected at delivery from 40 control pregnant women and 38 PCOS women with uncomplicated pregnancy. Women with PCOS were recruited at two medical centers and pregnant controls were recruited at one of these centers. Placental mRNA expression of genes encoding proteins related to steroid action, metabolic pathways and cytokines was analyzed by quantitative RT-PCR. Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western blot. Levels of sex steroids in serum were determined by mass spectrometry. Placental P-STAT3 (Tyr-705) was increased in women with PCOS (P < 0.05) versus controls. Placental mTOR signaling was not affected in PCOS women when compared with controls. Circulating levels of androstenedione, androst-5-ene-3β, 17β-diol, testosterone, 5α-dihydrotestosterone and etiocholanolone glucuronide were higher and estradiol lower in women with PCOS than in controls (all P < 0.05). No correlation between sex steroid levels in serum and P-STAT3 was observed. Women with PCOS and pregnancy complications were excluded to avoid the confounding effects of placental pathologies, which could modify STAT3 and mTOR signaling. Moreover, 97.4% of women with PCOS in the study displayed oligoamenorrhea at diagnosis. Thus, the current findings could be restricted to PCOS women with the oligo-anovulatory phenotype without pregnancy complications. Phosphorylation of STAT3 is increased in the placenta from women with PCOS and uncomplicated pregnancies, indicating that specific metabolic placental pathways are activated in the absence of obstetric and perinatal complications. The work was supported by the Swedish Medical Research Council (Project No. 2011-2732 and 2014-2775); Jane and Dan Olsson Foundation, Wilhelm and Martina Lundgrens's Science Fund; Hjalmar Svensson Foundation (E.S.-V and M.M.); Adlerbert Research Foundation; Swedish federal government under the LUA/ALF agreement ALFFGBG-136481 and 429501 and the Regional Research and Development agreement (VGFOUREG-5171, -11296 and -7861). MM thanks the Becas Chile Programme (Chile) and University of Chile for financial support through a postdoctoral fellowship. There are no competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human reproduction (Oxford, England). 01/2015;
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    ABSTRACT: To compare the effect of a single session of acupuncture with either low-frequency electrical or manual stimulation on insulin sensitivity and molecular pathways in the insulin-resistant dihydrotestosterone-induced rat polycystic ovary syndrome (PCOS) model. Both stimulations cause activation of afferent nerve fibers. In addition, electrical stimulation causes muscle contractions, enabling us to differentiate changes induced by activation of sensory afferents from contraction-induced changes.
    Acta Diabetologica 09/2014; · 3.68 Impact Factor
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    ABSTRACT: This review focuses on rodent models exposed to sex steroids prepubertally and describes their phenotypes and pathophysiology with specific focus on the estradiol valerate-, dihydrotestosterone-, and letrozole-induced rat polycystic ovary syndrome (PCOS) models. Phenotypic presentations are compared among models as a function of the timing and dose of the exposure. Furthermore, the use of these models to study the possible effects and mechanisms of different treatment modalities relevant for women with PCOS will be discussed. Importantly, we do not claim to review all available rodent models of PCOS. Despite the variety of rodent PCOS models currently available, there is no "gold standard" that mimics the complete range of abnormalities observed in women with PCOS. In this regard, it is important to select the most suitable model for the pathophysiological experiment to be performed or the treatment strategy to be tested. Important variables to take into consideration are dose, route of administration, timing and duration of exposure, and the relevance of the abnormalities of the reproductive and metabolic axes in the rodent model to those observed in human PCOS.
    Seminars in Reproductive Medicine 05/2014; 32(3):183-93. · 3.21 Impact Factor
  • Archivos de Medicina Veterinaria 12/2013; 46(1):13-21. · 0.41 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder associated with obesity and insulin resistance that often precedes the development of type-2 diabetes. Rats continuously exposed to dihydrotestosterone from prepuberty display typical reproductive and metabolic PCOS characteristics including anovulation, polycystic ovaries, insulin resistance, and obesity. Our aim was to investigate if resveratrol improves reproductive and metabolic functions in PCOS rats. The effect was compared to exercise. Control and PCOS rats were treated with vehicle or resveratrol (400 mg · kg(-1) · day(-1)) for 5-6 weeks. Another group of PCOS rats received vehicle treatment and exercised for 5-6 weeks. Insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp. The glucose infusion rate was lower in the PCOS-vehicle group compared to control-vehicle rats (P < 0.05). Exercise increased insulin sensitivity compared with PCOS-vehicle rats (P < 0.05), but resveratrol did not. Resveratrol treatment and exercise resulted in smaller adipocytes, upregulated estrogen-related receptor α gene expression in subcutaneous fat, and improved estrus cyclicity in the previously acyclic PCOS rats. Although resveratrol had positive effects on adiposity and cyclicity in a similar manner to exercise, resveratrol does not seem to be a good candidate for treating insulin resistance associated with PCOS because no improvement in insulin sensitivity was observed in PCOS rats on normal chow.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:964070. · 2.18 Impact Factor
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    Juan F Montiel, Heidy Kaune, Manuel Maliqueo
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    ABSTRACT: The conserved brain design that primates inherited from early mammals differs from the variable adult brain size and species-specific brain dominances observed across mammals. This variability relies on the emergence of specialized cerebral cortical regions and sub-compartments, triggering an increase in brain size, areal interconnectivity and histological complexity that ultimately lies on the activation of developmental programs. Structural placental features are not well correlated with brain enlargement; however, several endocrine pathways could be tuned with the activation of neuronal progenitors in the proliferative neocortical compartments. In this article, we reviewed some mechanisms of eutherians maternal-fetal unit interactions associated with brain development and evolution. We propose a hypothesis of brain evolution where proliferative compartments in primates become activated by "non-classical" endocrine placental signals participating in different steps of corticogenesis. Changes in the inner placental structure, along with placenta endocrine stimuli over the cortical proliferative activity would allow mammalian brain enlargement with a concomitant shorter gestation span, as an evolutionary strategy to escape from parent-offspring conflict.
    Frontiers in Neuroanatomy 01/2013; 7:22. · 4.18 Impact Factor
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    ABSTRACT: Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome.
    Endocrinology 11/2012; · 4.72 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate the placental activity of steroid sulfatase (STS), 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD-1) and P450 aromatase (P450arom) in polycystic ovarian syndrome (PCOS) compared to normal pregnant women. DESIGN: Twenty pregnant women with PCOS and 30 control pregnant women who delivered at term were studied. Samples of placental tissue and cord blood were obtained after delivery. A maternal blood sample was obtained during the 34th week of gestation. In placental tissue, the activities of STS, 3β-HSD-1 and P450arom were evaluated. In the blood samples, progesterone, DHEAS, DHEA, androstenedione, testosterone, estrone, estradiol and total estriol were determined. RESULT: In placental tissue from women with PCOS, higher 3β-HSD-1 and lower P450 aromatase activities were observed compared to control women. Moreover, women with PCOS showed higher androstenedione and testosterone concentrations compared to normal pregnant women (p=0.016 and p=0.025, respectively). In cord blood, female newborns of women with PCOS exhibited lower androstenedione and higher estriol concentrations compared to daughters of control women (p=0.038; p=0.031, respectively). CONCLUSION: These data suggest that placental tissue from women with PCOS shows changes in the activities of two important enzymes for steroid synthesis, higher 3β-HSD-1 and lower P450, which could increase androgen production during pregnancy.
    European journal of obstetrics, gynecology, and reproductive biology 11/2012; · 1.97 Impact Factor
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    ABSTRACT: Here we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg free testosterone from gestational day 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptors α and ß, androgen receptor, and 17 beta-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of non-alcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction, however at 6 weeks of age there was no difference in body weight between the offspring of testosterone-, and control-treated rats. At 10-11 weeks of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams and they developed non-alcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.
    AJP Endocrinology and Metabolism 10/2012; · 4.51 Impact Factor
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    ABSTRACT: The polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder that arise from a combination of genetic and environmental factors. To assess the role of the androgen receptor (AR) CAG repeat polymorphism in the metabolic and reproductive features in daughters of women with PCOS (PCOSd). Sixty-seven PCOSd and 60 daughters of control women (Cd) were studied in early stages of sexual development. Sex steroids, glucose, insulin and lipids were determined. The AR CAG repeat sizes and X-chromosome inactivation (XCI) were analyzed. PCOSd and Cd had similar mean number of CAG repeats and XCI pattern. In PCOSd and Cd, methylation-weighted biallelic means CAGn (mwCAGn) was not associated with androgen levels. In infants and pubertal PCOSd, mwCAGn was associated with a low concentration of HDL-cholesterol. AR CAG repeat polymorphism appears to be unrelated with serum androgen levels. However, the short mwCAGn variant may have a possible impact on the lipid profile in PCOSd.
    Gynecological Endocrinology 07/2012; 28(7):516-20. · 1.14 Impact Factor
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    ABSTRACT: To evaluate in a cross-sectional study adiponectin and leptin levels in prepubertal and pubertal daughters of women with PCOS and their relationship to insulin sensitivity and reproductive features. We studied 92 daughters of PCOS women (PCOSd) and 76 daughters of control women (Cd) matched by age and body mass index SD scores and distributed according to breast Tanner stage: prepuberty (Tanner 1), early puberty (Tanner 2-3) or late puberty (Tanner 4-5). In all girls an oral glucose tolerance test was performed. Leptin, adiponectin, sex steroids, SHBG, glucose, insulin and lipid profile were determined. Leptin-adiponectin ratio, free androgen index and insulin sensitivity (HOMA-IR and ISI composite) were then calculated. Prepubertal PCOSd showed lower serum adiponectin compared to Cd (p=0.028), whereas during puberty no differences were observed between the groups. Leptin concentrations were similar in both groups in all Tanner stages. In addition, in PCOSd during early puberty, adiponectin showed a negative correlation with testosterone and leptin showed a negative correlation with ISI composite, which were independent of BMI SDS (r=-0.39; p=0.02 and r=-0.42; p=0.01). These observations suggest that during the prepubertal period PCOSd exhibit abnormal adiponectin levels, independently of BMI. Moreover, leptin and adiponectin may be related to metabolic and reproductive abnormalities observed in PCOSd during the early stages of sexual development.
    European journal of obstetrics, gynecology, and reproductive biology 03/2012; 161(1):56-61. · 1.97 Impact Factor
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    ABSTRACT: We have previously described increased serum levels of anti-Müllerian hormone (AMH) and stimulated insulin in daughters of women with polycystic ovary syndrome (PCOS), suggesting that these girls may have an altered ovarian follicular development which may be modulated by insulin. However, the specific relationship between serum AMH and insulin levels during each Tanner stage of puberty in this cohort has not been established. The aim of our study was to establish the relationship between AMH and poststimulated insulin serum concentrations during each stage of puberty in daughters of women with PCOS (PCOSd), compared to daughters of control women (Cd). We studied 135 PCOSd and 93 Cd classified according to their Tanner stage. Gonadotrophins, sex steroids, sex hormone-binding globulin (SHBG), and AMH were determined in a fasting sample. Ovarian volume was measured by pelvic ultrasound. In addition, in both groups we performed an oral glucose tolerance test with measurements of glucose and insulin. Anti-Müllerian hormone levels were significantly higher in PCOSd compared to Cd at all Tanner stages. Daughters of women with PCOS having AMH concentrations greater than 2 standard deviation (SD) above the mean AMH value for the Cd group showed decreased serum follicle-stimulating hormone (FSH) concentrations and increased stimulated levels of insulin during Tanner stages I, II, and III. Anti-Müllerian hormone levels are increased in PCOSd during all stages of puberty. We suggest that those PCOSd with the highest AMH levels probably represent a group of girls with more severe ovarian dysfunction and metabolic derangements.
    Reproductive sciences (Thousand Oaks, Calif.) 02/2012; 19(4):383-90. · 2.18 Impact Factor
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    ABSTRACT: To evaluate the ovarian function during early infancy in daughters of women with polycystic ovary syndrome (PCOS) treated with metformin throughout pregnancy (PCOSd+M), as a means to reduce androgen and insulin levels, compared with daughters of nontreated PCOS women (PCOSd-M) and daughters of women who belong to a healthy comparison group (HCd). Descriptive and analytic study. Unit of endocrinology and reproductive medicine. Fifteen PCOSd+M, 23 PCOSd-M, and 35 HCd were studied at 2-3 months of age. A GnRH analogue test was performed with determinations of gonadotropins, sex steroids, SHBG, and anti-Müllerian hormone (AMH). Differences in AMH levels between PCOSd+M, PCOSd-M and HCd. AMH and peak E(2) concentrations were significantly higher in PCOSd-M compared with HCd, whereas PCOSd+M exhibited AMH concentrations and peak E(2) levels similar to those observed in HCd. The improvement of the altered endocrine-metabolic environment of PCOS mothers reduces AMH levels in their daughters, which might reflect a decrease in their follicular mass.
    Fertility and sterility 11/2011; 97(1):218-24. · 4.30 Impact Factor
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    ABSTRACT: Exposure to excess testosterone (T) during fetal life has a profound impact on the metabolic and reproductive functions in the female's postnatal life. However, less is known about the effects of excess testosterone in males. The aim of the present study was to evaluate the impact (consequences) of an excess of T during fetal development on mature male testis. The testicular evaluation was by histological analysis and by determination of mRNA expression of the FSH receptor (FSH-R), transforming growth factor-β type I receptor (TβR-I), and two members of the TGF-β superfamily, transforming growth factor-β3 (TGFβ3) and anti-Müllerian hormone (AMH) in males born to mothers receiving an excess of T during pregnancy. At 42 wk of age, postpubertal males born to mothers treated with 30 mg of T propionate twice weekly from day 30 to 90, followed by 40 mg of T propionate from day 90 to 120 of pregnancy (T males), showed higher concentrations of FSH in response to a GnRH analog, a higher number of Sertoli cells/seminiferous tubule cross-section, and a lower number of germ cells/tubules (P < 0.05) than control males (C males) born to mothers treated with the vehicle. The mRNA expression of FSH-R and of TβR-I was higher in T males compared with C males (P < 0.05). Moreover, in T males, AMH expression level correlated negatively with the expression level of TGFβ3. In C males, this latter correlation was not observed. These results suggest that prenatal exposure to an excess of T can negatively modify some histological and molecular characteristics of the mature testis.
    AJP Endocrinology and Metabolism 12/2010; 299(6):E998-E1005. · 4.51 Impact Factor
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    ABSTRACT: Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes. To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by auto-antibodies. Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22-28, a 2-h, 75 g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies. A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCOS women. A highly prevalence of anti-GAD65 was observed in women with GDM which is in agreement with previous studies. Nevertheless, the frequency of these auto-antibodies was very low in NP and PPCOS women.
    Gynecological Endocrinology 12/2010; 26(12):889-93. · 1.14 Impact Factor
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    ABSTRACT: Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes. To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by auto-antibodies. Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22-28, a 2-h, 75 g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies. A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCOS women. A highly prevalence of anti-GAD65 was observed in women with GDM which is in agreement with previous studies. Nevertheless, the frequency of these auto-antibodies was very low in NP and PPCOS women.
    Gynecological Endocrinology 12/2010; 26(12):889-93. · 1.14 Impact Factor
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    ABSTRACT: Context: We previously demonstrated that low birth weight (BW) infant girls show increased serum anti-Müllerian hormone (AMH) concentrations and poststimulated estradiol levels compared to normal-BW infants, suggesting an altered follicular development. However, the impact of high BW on reproductive function is less known. Objective: To evaluate the effect of BW on AMH, we determined the concentrations of this hormone in low-BW, normal-BW, and high-BW female infants during the first 3 months of life. Design: Twenty-seven low-BW, 29 normal-BW, and 28 high-BW infant girls were studied. We measured serum gonadotropins, steroid hormones, AMH, glucose, insulin, free fatty acids, IGF-I, and adiponectin in a fasting blood sample. In addition, in a subgroup of normal-BW (n = 23) and high-BW infants (n = 10), a GnRH analog leuprolide acetate test was performed. Results: Serum concentrations of AMH were higher in low-BW and high-BW infants compared to normal-BW infants (P = 0.028 and 0.022, respectively). In addition, in high-BW infants, adiponectin concentrations were lower (P = 0.018), and poststimulated FSH and estradiol levels were higher compared to normal-BW infants (P = 0.024 and 0.047, respectively). Conclusions: Serum AMH and poststimulated estradiol concentrations are increased in low-BW and high-BW female infants, suggesting that these girls may show evidence of an altered follicular development. However, the increased poststimulated FSH levels and low adiponectin concentrations observed in high-BW infants suggest that ovarian function is perturbed through a different mechanism from that in low-BW infants.
    The Journal of Clinical Endocrinology and Metabolism 11/2009; 95(2):903-10. · 6.31 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is characterized by the presence of hyperandrogenism and an increased follicular mass probably determined by deregulation of locally produced factors. Anti-Müllerian hormone (AMH) is a glycoprotein that inhibits follicular recruitment and determines the size of the follicular pool. To evaluate the role of androgens in the regulation of AMH expression in bovine granulosa cells from small follicles, granulosa cells from 3 to 4 mm follicles were isolated and incubated in basal culture media, or in media containing testosterone (T) at 10(-5)M, T 10(-8)M, or estradiol (E2) at 150 ng/ml for 48 h. AMH mRNA levels of these cells were determined using real-time PCR (RT PCR). AMH protein levels and E2 were determined in cell-conditioned media. A 3.4-fold decrease in AMH mRNA levels was observed in granulosa cells exposed to T 10(-5)M (P = 0.03, n = 5), but not in cells exposed to T 10(-8)M. AMH protein levels showed a 1.8-fold reduction in cell-conditioned media from cells exposed to T 10(-5)M (P = 0.01, n = 5), without significant changes in the group exposed to T 10(-8)M. Cells treated with E2 150 ng/ml showed no change in AMH protein levels. We propose that AMH expression is modulated by androgens in bovine granulosa cells from small follicles. Thus, it is possible to speculate that androgens, by inhibiting AMH expression, may promote follicle recruitment, increasing the early growing follicular pool. This new mechanism may have implications for the understanding of PCOS pathophysiology.
    Endocrine 09/2009; 36(2):339-45. · 3.53 Impact Factor
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    ABSTRACT: In some patients, PCOS may develop as a consequence of an exaggerated adrenarche during pubertal development. The aim of the study was to assess adrenal function during childhood and pubertal development in daughters of women with PCOS (PCOSd). We included 98 PCOSd [64 during childhood (ages 4-8 yr) and 34 during the peripubertal period (ages 9-13 yr)] and 51 daughters of control women (Cd) [30 during childhood and 21 during the peripubertal period]. In both groups, an acute ACTH-(1-24) stimulation test (0.25 mg) and an oral glucose tolerance test were performed. Bone age and serum concentrations of cortisol, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), glucose, and insulin were determined. PCOSd and Cd were similar in age and body mass index. During the peripubertal period, basal and poststimulated DHEAS concentrations were higher in PCOSd compared to Cd. Among PCOSd, 12.5% of girls in childhood and 32.4% in peripuberty presented biochemical evidence of exaggerated adrenarche. Stimulated insulin was higher in PCOSd compared to Cd during childhood (P = 0.03) and peripuberty (P = 0.03). An advancement of 8 months between bone and chronological age was observed in peripubertal PCOSd compared to Cd. In PCOSd, basal and stimulated DHEAS concentrations were higher during the onset of puberty. Around 30% of the PCOSd demonstrated an exacerbated adrenarche, which may reflect increased P450c17 activity. In addition, a modest advance in bone age was observed, probably secondary to the hyperinsulinemia and/or adrenal hyperandrogenism.
    The Journal of Clinical Endocrinology and Metabolism 07/2009; 94(9):3282-8. · 6.31 Impact Factor
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    ABSTRACT: A significant proportion of the first-degree female relatives of women with polycystic ovary syndrome (PCOS) may be at risk for developing PCOS. However, it is not known at which stage of pubertal development the hormonal and metabolic abnormalities ensue in PCOS. The aim of the study was to assess the reproductive and metabolic profiles of daughters of women with PCOS (PCOSd) during the peripubertal period, a stage during which the gonadal axis is activated and PCOS may become clinically manifest. Ninety-nine PCOSd [30 prepubertal and 69 pubertal (Tanner II-V)] and 84 daughters of control women (Cd) (20 prepubertal and 64 pubertal) were studied. An oral glucose tolerance test, a GnRH agonist test (leuprolide acetate, 10 microg/kg sc), and a transabdominal ultrasound were performed. Gonadotropins, sex steroids, SHBG, glucose, insulin, and lipids were determined. Both groups had similar chronological ages and body mass index sd scores according to Tanner stage distribution. Ovarian volume and 2-h insulin were significantly higher in PCOSd compared to Cd at all Tanner stages. In Tanner stages IV and V, basal testosterone and poststimulated LH, testosterone, and 17-hydroxyprogesterone concentrations were significantly higher in PCOSd compared to Cd. Hyperinsulinemia and an increased ovarian volume are present in PCOSd before the onset of puberty and persist during pubertal development. The biochemical abnormalities of PCOS appear during late puberty. Considering the early onset and the nature of the alterations, PCOSd constitute a high-risk group for metabolic and reproductive derangements.
    The Journal of Clinical Endocrinology and Metabolism 03/2009; 94(6):1923-30. · 6.31 Impact Factor

Publication Stats

776 Citations
183.67 Total Impact Points

Institutions

  • 2012–2013
    • University of Gothenburg
      • Department of Physiology
      Goeteborg, Västra Götaland, Sweden
  • 2000–2013
    • University of Santiago, Chile
      • Departamento Clínico de Medicina Interna
      CiudadSantiago, Santiago, Chile
  • 1999–2009
    • University of Chile
      • Facultad de Medicina
      CiudadSantiago, Santiago, Chile
  • 2007–2008
    • Hospital San Juan de Dios
      CiudadSantiago, Santiago, Chile
  • 2001–2005
    • Hospital San Juan de Dios Pamplona
      Quilichao, Cauca, Colombia