Oestrogen activity of the serum in adolescents with Type 1 diabetes.

AIMS: To assess serum oestrogen levels and oestrogenic activity in adolescents with Type 1 diabetes compared with a healthy control group. METHODS: We conducted a cross-sectional study that evaluated adolescents with Type 1 diabetes (n = 38) and healthy adolescents (control group; n = 32). Serum oestrogens, urinary oestrogen metabolites and serum oestrogenic activity were assessed. Oestrogenic activity was evaluated in an in vitro cell proliferation assay using a modified E-screen assay with MCF-7/BUS cells. RESULTS: Adolescents with Type 1 diabetes had lower oestrogenic activity levels in both phases of the menstrual cycle compared with the control group (follicular phase: 76 vs 94%; luteal phase: 97 vs 131%; P < 0.01), even after adjusting for BMI, oestradiol and oestrone levels. Postmenarcheal adolescents with Type 1 diabetes had lower oestradiol levels compared with control subjects in the follicular phase (63.3 pmol/l vs 89.4 pmol/l; P < 0.01) and higher oestrone levels compared with controls in the luteal phase (196 vs 151.9 pmol/l; P < 0.05). CONCLUSIONS: Adolescents with Type 1 diabetes had lower levels of serum oestrogenic activity, and these were lower than expected based on their serum oestradiol levels. We postulate that changes in the serum milieu of oestrogens in patients with Type 1 diabetes may explain their decreased oestrogenic activity and may play a role in their adverse metabolic profile.

C-Reactive protein and insulin growth factor 1 serum levels during the menstrual cycle in adolescents with Type 1 diabetes.

AIMS: To evaluate C-reactive protein, insulin growth factor 1 and lipid levels during the follicular and luteal phases in adolescents with Type 1 diabetes. METHODS: Adolescents with Type 1 diabetes (N = 40) and healthy controls (C; N = 43) were studied during the follicular and luteal phases of their menstrual cycles. C-Reactive protein, insulin growth factor 1 and lipid levels were measured. RESULTS: Adolescents with Type 1 diabetes exhibited higher C-reactive protein levels than the C group during the follicular (P < 0.0001) and luteal phases (P < 0.01). The elevation of C-reactive protein levels was more pronounced in overweight adolescents with Type 1 diabetes than in adolescents in the C group. More adolescents with Type 1 diabetes were classified as having an elevated risk of cardiovascular disease (C-reactive protein > 3 mg/l) in the luteal phase than in the follicular phase (37.5% and 17.5%, respectively); half of the overweight adolescents with Type 1 diabetes in the luteal phase reached this level. BMI was the only significant factor affecting follicular and luteal phase C-reactive protein levels in adolescents with Type 1 diabetes. Lower insulin growth factor 1 levels were observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes compared with controls. An elevation in insulin growth factor 1 levels in the luteal phase relative to the follicular phase was observed in controls, but not in adolescents with Type 1 diabetes. Luteal insulin growth factor 1 and C-reactive protein exhibited an inverse correlation (r = -0.4, P = 0.01). CONCLUSIONS: Adolescents with Type 1 diabetes have higher C-reactive protein levels and lower insulin growth factor 1 levels relative to controls, especially during the luteal phase. Type 1 diabetes diminishes the natural elevation in insulin growth factor 1 levels observed during the luteal phase in controls. Excess weight exacerbates the subclinical inflammatory state observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes.

Cortisol hyporesponsiveness to the low dose ACTH test is a frequent finding in a pediatric population with type 1 diabetes mellitus.

INTRODUCTION: In adults with type 1 diabetes mellitus (DM1), a 25% of risk of hypocortisolism has been found through a low dose ACTH test with negative antibodies suggesting other causes of hypothalamic-pituitary-adrenal axis dysfunction. AIM: To evaluate adrenal function in pediatric patients with DM1 and correlate the results with the frequency of hypoglycemia and metabolic control. METHODS: Sixty-nine patients were enrolled, age 12.3 (5.7-18.1); 50 boys and 19 girls. A 20% had additional autoimmune diseases. Mean hemoglobin A1c (HbA1c) was 8.1% and insulin dose was 1.14 U/kg/d. After an overnight fast, a low dose ACTH test (1 µg) was performed. Basal and stimulated cortisol concentrations, DHEAS, and plasma renin activity (PRA) were measured. A cortisol response post-ACTH below 18 µg/dL was considered abnormal. RESULTS: 58% of the tested patients had an abnormal response to ACTH test. These patients also had lower DHEAS concentrations, but were not different in diabetes duration, HbA1C, severe hypoglycemia, ACTH, or PRA concentrations compared to those who had a normal cortisol post-ACTH. One patient out of 59, had a positive anti-21-hydroxylase antibody (21OHA) and presented a poor response to ACTH. CONCLUSIONS: We found a significant proportion of our patients having a subnormal cortisol response independent of the presence of anti-adrenal cell antibodies. We did not find a correlation with metabolic control, probably due to the good metabolic control of this group. The absence of 21OHA does not rule out subclinical hypocortisolism in this population. Our results suggest testing adrenal function in children with DM1.

Differences in Expression, Content, and Activity of 11ß-HSD1 in Adipose Tissue between Obese Men and Women.

Cortisol production in adipose tissue is regulated by 11ß-HSD1. Objective. To determine whether there are differences in gene expression, enzyme activity, and protein content of the 11ß-HSD1 enzyme in VAT (visceral adipose tissue) and SAT (subcutaneous adipose tissue) from obese compared to nonobese adults. Methods. VAT and SAT samples were obtained from 32 obese subjects (BMI > 30 Kg/m(2)) who underwent bariatric surgery and 15 samples from controls submitted to elective surgery. Fasting serum glucose, insulin, and lipids were measured. The expression of 11ß-HSD1 was determined by RT-PCR, the enzyme activity by thin-layer chromatography, and the protein content by Western blot. Results. Obese patients had higher cholesterol, insulin, and HOMA-IR compared to nonobese. There were no differences in VAT or SAT expression of 11ß-HSD1 between obese and nonobese patients. However, we found lower 11ß-HSD1 activity and protein content in VAT, in obese women versus nonobese women (P < 0.05). BMI and 11ß-HSD1 enzyme activity and protein content in VAT correlated inversely in women. Conclusions. Regulation of 11ß-HSD1 activity in VAT from obese subjects appears to be gender specific, suggesting the existence of a possible protective mechanism modulating this enzyme activity leading to a decrease in the production of cortisol in this tissue.

Early onset of primary hypogonadism revealed by serum anti-Müllerian hormone determination during infancy and childhood in trisomy 21.

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2months-20year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.

Polycystic ovarian morphology in adolescents with regular menstrual cycles is associated with elevated anti-Mullerian hormone.

BACKGROUND: The significance of polycystic ovarian morphology (PCOM) during adolescence is not clear. The aim of this study was to determine the relationship between PCOM and anti-Müllerian hormone (AMH), inhibin B, testosterone and insulin levels in healthy girls during the second decade of life. We also determined whether AMH could be used as a surrogate marker of PCOM during adolescence. METHODS: Seventy-four non-obese adolescents (age range: 13.5-19.75 years old) with regular menstrual cycles participated in this study. Transabdominal ultrasound and blood samples were obtained during the follicular phase. RESULTS: PCOM was present in 33.8% of the subjects. Girls with PCOM had higher AMH levels than girls without PCOM (72.5 ± 6.1 versus 33.4 ± 2.6 pmol/l; P < 0.0001) and lower FSH levels (5.4 ± 0.3 versus 6.2 ± 0.2 mUI/ml; P < 0.036). Similar levels of inhibin B, androgens and LH were observed in girls with and without PCOM. PCOM prevalence and AMH levels were not associated with age (P = 0.745 and 0.2, respectively) or BMI-SDS (P = 0.951 and 0.096, respectively). AMH levels positively correlated with the of 2-5 mm follicle number. AMH levels ≥ 60.15 pmol/l had a sensitivity and specificity of 64.0 and 89.8%, respectively, to diagnose PCOM (area under the curve = 0.873). CONCLUSIONS: These data confirm that PCOM in healthy non-hyperandrogenic girls with regular menstrual cycles is prevalent and is not associated with hyperandrogenism. The elevated AMH and lower FSH levels observed in healthy girls with regular menses and PCOM suggest that this ovarian pattern is secondary to a larger number of 2-5 mm follicles. An elevated AMH level is suggestive of the presence of PCOM during adolescence.

[Morbidity and risk factors of transrectal prostate biopsy]. / Morbilidad y factores de riesgo de la biopsia transrectal prostática.

OBJECTIVES: To evaluate the incidence of minor complications that rarely need treatment (haematuria, hematospermia and rectal bleeding) and major complications (fever and shock) in patients undergoing transrectal biopsy of the prostate and to identify risk factors. PATIENTS AND METHODS: We present an analytic and prospective study where we evaluated 146 patients subjected to transrectal biopsy of the prostate from December 2007 to September 2008. Complications rates and variables were analyzed. RESULTS: Eight patients (5,5%) suffered fever and seven (4,8%) of them were admitted. One of the patients (0,7%) suffered shock. The median of time between biopsy and fever was 3.5 days (1-10 days). Haematuria and hematospermia were more frequent in patients younger than 65 years (p<0.05) and fever and sepsis were more frequent in patients with prostate volume smaller than 55mL (p<0.05). CONCLUSIONS: The complications of the transrectal biopsy of the prostate are frequent, autolimited and they rarely suppose a health hazard for the patients. The most frequent are haematuria and hemospermia, specially in younger patients, whereas infectious complications are rarer and in our study are more frequent in patients with smaller prostates. We must take into account that the information to the patient is very important after a prostate biopsy, so we can avoid useless consultations (for example with haematuria) and it will enable to identify important signs like fever earlier.

Expression and protein content of IGF-I and IGF-I receptor in placentas from small, adequate and large for gestational age newborns.

In humans, a direct relationship between IGF-I cord blood levels and birth weight has been demonstrated. To determine the placental IGF-I, IGF-II and IGF-IR mRNA and protein contents in full-term pregnancies from appropriate for gestational age (AGA), small for gestational age (SGA) and large for gestational age (LGA) newborns, we studied the placentas from 35 AGA, 30 SGA and 28 LGA pregnancies. The IGF-I, IGF-II and IGF-I receptor (IGF-IR) placental mRNA and protein contents were determined in the basal and chorionic plates of the placenta. IGF1 and IGF1R mRNA was higher in SGA compared to AGA and LGA placentas and lower in LGA compared with AGA placentas. In addition, a higher protein content of IGF-I and IGF-IR was observed in SGA compared with AGA and LGA placentas and lower contents in LGA compared with AGA placentas. These results suggest that the higher IGF-I and IGF-IR contents observed in SGA placentas and the lower contents observed in LGA placentas compared with AGA placentas may be influencing human fetal growth.

[Does cystocele have a role in bladder outlet obstruction]. / ¿Es realmente el cistocele un factor de obstrucción infravesical?

INTRODUCTION: Controversy exists as to whether cystocele has a causative role in bladder outlet obstruction (BOO). OBJECTIVE: To assess the relationship between cystocele and bladder outlet obstruction. MATERIALS AND METHODS: Two hundred women undergoing a urodynamic study from December 2007 to December 2008 were retrospectively assessed. Patients were divided into two groups: Group A: Patients with no cystocele (Grade 0) and Grade I cystocele Group B: Patients with Grade II-IV cystocele. EXCLUSION CRITERIA: 1. Absence of flowmetry or voided volume < 150 ml. 2. Neurological disorders. 3. History of urogenital surgery. Bladder outlet obstruction was defined as follows: Postvoid residue (PVR) > 20%; peak flow (Qmax) < 15 ml/sec; detrusor pressure at maximum flow (PdetQmax) > 25 cm H2O. RESULTS: Group A included 64% of patients, and Group B the remaining 36%. A pathological PVR > 20% was found in 26.6% and 40.3% of patients in Group A and Group B respectively (p=0.04). A Qmax < 15 mL/sec was seen in 15.6% and 27.8% of Group A and Group B patients respectively (p=0.03). A PdetQmax > 25 cm H2O was found in 26.3% and 47.8% of Group A and Group B patients respectively (p=0.01). CONCLUSIONS: A statistically significant association exists between cystocele and bladder outlet obstruction.

Leuprolide acetate gonadotrophin response patterns during female puberty.

OBJECTIVE: To assess normative data and the usefulness of spontaneous and LHRH analogue-stimulated serum LH and FSH levels measured by immunoradiometric assays (IRMA) in the evaluation of normal puberty. DESIGN: Prospective. Healthy girls in Tanner I and Tanner II from the local community were invited to participate (n = 47). METHODS: A leuprolide acetate test (500 mcg/m(2); sc) was performed. LH and FSH levels were determined using IRMA. Tanner II girls were assessed every 6 months until Tanner V. Girls who progressed from Tanner II to Tanner III in the next 6 months were called Tanner II-2; otherwise, they were called Tanner II-1. RESULTS: The prepubertal upper limit (CI 95%) was 0.49 IU/l for basal LH and 5.1 IU/l for stimulated LH. Taking into account these LH cut-off limits, 72.2% and 66.7% of Tanner II-1 and 41.6% and 41.7% of Tanner II-2 subjects presented overlapping values for basal and stimulated LH, respectively, as compared with the Tanner I group. The cut-offs for basal and stimulated LH to predict progression from Tanner II to Tanner III in the next 6 months were a basal LH level > or =0.49 IU/l (Sensitivity = 0.58; 1-Specificity = 0.33) and a poststimulated LH level > or =4.75 IU/l (Sensitivity = 0.67; 1-Specificity = 0.44). CONCLUSION: According to an IRMA, the basal and leuprolide acetate gonadotrophin response patterns during the beginning stages of puberty overlapped between Tanner I and Tanner II, and the cut-offs of basal and stimulated LH levels to predict progress from Tanner II to Tanner III had low sensitivities for the following 6 months.

Differences in expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 and 2 in human placentas of term pregnancies according to birth weight and gender.

BACKGROUND: Fetal exposure to maternal glucocorticoids may determine fetal growth and the programing of later disorders. Availability of the glucocorticoids in the placenta is regulated by the 11beta-hydroxysteroid dehydrogenase (11beta-HSDs) enzymes. To date, there are discrepancies with regard to cortisol (F) cord blood levels in fetuses with intrauterine growth retardation in different species. Objective To study the expression and activity of 11beta-HSDs in placentas from full term small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) newborns, and cortisol cord blood concentration. METHODS: Twenty-five placentas from AGA, 24 SGA and 25 LGA were collected. RESULTS: SGA newborns had significantly lower and LGA newborns had significantly higher birth weight, birth length, head circumference, and placental weight than AGA counterparts. We observed a direct correlation between placental weight and birth weight, birth length and head circumference, and higher cord F levels in SGA newborns. The 11beta-HSD1 expression was similar among the SGA, AGA, and LGA placentas. However, within the placentas of SGA newborns, the 11beta-HSD1 mRNA levels were significantly reduced in the chorionic plate compared with basal plate. An inverse correlation between cord F levels and activity of 11beta-HSD1 in the chorionic plate of the SGA placentas was detected. The 11beta-HSD2 activity was seven- to eightfold higher compared with 11beta-HSD1 in the placentas, and there was a lower 11beta-HSD2 activity in females' SGA placentas compared with the male SGA placentas. CONCLUSION: We observed a lower expression and activity of 11beta-HSD1 in the chorionic plate of the SGA placentas, suggesting a possible compensatory mechanism to diminish the higher cortisol fetal concentrations observed in fetuses with intrauterine growth restriction.

Carotid intima-media thickness as a cardiovascular risk marker in pediatric end-stage renal disease patients on dialysis and in renal transplantation.

Cardiovascular diseases are the principal cause of morbidity and mortality among young adults with chronic renal disease. Atherosclerotic structural changes as detected by high-resolution B-mode ultrasonography preceed clinical findings by several decades. The carotid intima-media thickness (cIMT) is being used as a marker of early atherosclerosis. We determined the cIMT of common carotid artery (CCA) in 8 asymptomatic children on dialysis or 12 after renal transplantation for comparison with 30 healthy controls. This prospective study of 40 children showed a mean age of 13.5 years (range, 8 to 18). We evaluated cIMT, hemoglobin, serum creatinine levels, lipid profile, and homeostasis model assessment (HOMA). The statistical analysis for variables with normal distribution was Student's t test. Parameters with a non-normal distribution were evaluated by the Mann-Whitney or Spearman correlation analysis with P < .05 considered statistically significant. The mean measurements of cIMT (mm) of both CCA were dialysis 0.450 +/- 0.042; transplant 0.467 +/- 0.033, and controls 0.380 +/- 0.009 (P < .03). The homa levels of 2.45 +/- 0.98 for dialysis and 1.8 +/- 0.62 for transplant, were both significantly higher than the control group (0.8 +/- 0.09; P < .01). The Ca x P product was higher in dialysis vs transplant group: 63.0 +/- 10.0 versus 46.2 +/- 2.2 (P < .03). The intact parathyroid hormone levels were 666.7 +/- 276.7 versus 44.2 +/- 2.8, respectively (P < .008). The low-density lipoprotein cholesterol was 129.0 +/- 23.1 versus 80.8 +/- 10.6, respectively (P < .04). The cIMT correlated with the duration of dialysis before transplantation. Changes in IMT can be detected by ultrasonography in early childhood in uremic patients. The etiology of atherosclerosis is multifactorial in children with end-stage renal disease. It seems possible to prevent or improve the factors related to cardiovascular risk in these patients.

Deficiencia somatotrófica en niños: características clínicas y bioquímicas según la etiología en 75 casos / Somatotrophic deficiency in children: report of 75 cases

Somatotrophic deficiency (SDMT) can be due to a deficiency of growth hormone releasing hormone(GHRH), growth hormone (GH) or insulin like growth factor I (IGF-I). Although its clinical features have been thoroughly described, the diagnosis is still controversial. Now there is an effective treatment with GH or IGF-I for these patients. AIM: To analyze the main clinical, etiological and laboratory characteristics of 75 SD patients (44 males), aged 9.4 + 4.5 years, with severe growth retardation. The diagnosis was confirmed by the lack of response to two GH stimulation tests (Clonidine, Glugagon or Insulin) and low levels of IGF-I or insulin-like growth factor binding protein- 3 (IGFBP-3). RESULTS: In 34 patients (46 percent), the cause of DSMT was considered idiopathic (DSMT-I), in 31 (41 percent) there was an organic cause (DSMT-O), most commonly caused by malformations or pituitary tumors and in 10 (13 percent), it was genetic (DSMT-G) (three patients with Laron's Syndrome, five with mutations of GH gene and 2 with probable mutations of Prop-1 and Pit-1 genes). IGF-1 levels, were significantly lower in DSMT-O and DSMT-G thanin DSMT-I (21.2 +/- 46.1, 23.4 +/-30.3 ng/mL and 50.2 +/- 48.3 ng/mL, respectively). The lowest height score corresponded to DSMT-G, compared to DSMT-O and DSMT (­5.7 +/- 0.9, -4.0 +/- 1.6 and ­4.3 +/- 1.2 DS, respectively) CONCLUSIONS: The high percentage of organic and genetic etiologies in our patients can be due to the systematic search of these diseases. DSMT-G (Laron, mutations in GH and Pit-1 genes) had the most severe growth retardation.

Comparison of leptin levels, body composition and insulin sensitivity and secretion by OGTT in healthy, early pubertal girls born at either appropriate- or small-for-gestational age.

BACKGROUND: Small for gestational age (SGA) has been associated with decreased insulin sensitivity (IS). A possible mechanism is the postnatal development of a metabolically disadvantageous body composition (BC). AIM: To determine whether there are differences between IS and BC in girls in early puberty who were SGA (birth weight < 10th percentile) or appropriate for gestational age (AGA, 10th-90th percentile). METHODS: Age-matched (SGA/AGA) early pubertal girls (Tanner II) were recruited from local schools. We determined waist circumference (WC), the sum of four skinfolds (S4S), and per cent fat mass (fat %) by impedanciometry. Leptin and OGTT assays were performed. The insulinogenic index (I-In), HOMA-IR (homeostasis model assessment of insulin resistance) and WBISI (whole body insulin sensitivity) were calculated. RESULTS: Median age (interquartile range) for 30 SGA and 35 AGA girls was 10.2 (1.1) vs. 9.8 (0.9), respectively (P = NS). BMI percentiles were 62.6 (56) vs. 67.4 (39); WC 60.5 (9.5) vs. 62.2 (6.5) cm; S4S 52 (30) vs. 52.2 (29.5) cm, and fat %[26.2 (6.7) vs. 28.5 (6.3)] was similar in both groups. SGA girls had higher leptin levels [15.4 (9.7) vs. 9.6 (11) ng/ml; P = 0.01] and I-In [2.05 (1.86) vs. 1.47 (1.27) microU/ml* mg/dl; P = 0.02]. No differences between HOMA-IR [2.07 (1.26) vs. 2.04 (1.4)] and WBISI [5.3 (3.3) vs. 5.1 (3.1)] were found between groups. CONCLUSION: The higher leptin level and I-In in girls born SGA at the beginning of puberty may be early indicators of an underlying subtle degree of insulin resistance, despite similar BMI and BC to AGA girls.

Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation.

A new triptorelin 11.25 mg long depot formulation is now available for the treatment of central precocious puberty (CPP). The aim of our study was to evaluate the efficacy of triptorelin 11.25 mg administered every 90 days to suppress gonadotropin and sex steroid secretion and pubertal signs in children with CPP during 2 years of treatment. Inclusion criteria were clinical pubertal development before the age of 8 years in girls or 9 years in boys, advanced bone age and a pubertal LH response (peak >5 mIU/ml) to GnRH. We studied 20 patients (19 girls and 1 boy), with a median age at entry into the study of 7.5 +/- 0.2 years for girls, and 9 years for the boy. The basal and GnRH-stimulated serum levels of LH and FSH decreased significantly from baseline to 3 months of therapy (p <0.0001). All patients had a GnRH-stimulated peak below 3 mIU/ml between 6 and 24 months of treatment. The pituitary-gonadal axis recovered adequately after discontinuation of therapy. These results suggest that 3-month depot triptorelin is a satisfactory alternative for the therapy of children with CPP. The longer interval between injections may increase acceptability and compliance with treatment.

Comparison of clinical, ultrasonographic, and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age or appropriate for gestational age: preliminary results.

CONTEXT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). OBJECTIVE: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children.

AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestational-age (SGA) at birth may be a consequence of rapid early postnatal weight gain. MATERIALS AND METHODS: We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). RESULTS: Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol(-1) l(-1), p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). CONCLUSIONS/INTERPRETATION: SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.

Regulation of steroid synthesis and apoptosis by insulin-like growth factor I and insulin-like growth factor binding protein 3 in human corpus luteum during the midluteal phase.

The aim of the present study was to investigate the action of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) on steroidogenesis and apoptosis in human corpus luteum during the midluteal phase. Slices from corpora lutea were incubated for 4 h with IGF-I or IGFBP-3. Progesterone, oestradiol, androstenedione and testosterone concentrations were determined by radioimmunoassay; caspase 3 expression was assessed by immunohistochemistry; bcl-2, bax and P(450arom) expression were assessed by RT-PCR; and apoptosis was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. The results showed that addition of IGF-I stimulated progesterone production (150%, P < 0.01), oestradiol production (65%, P < 0.05) and bcl-2 gene expression (approximately 200%, P < 0.05), but decreased apoptosis (P < 0.05). In contrast, IGFBP-3 reduced steroid production and increased bax gene expression and the percentage of apoptotic cells (P < 0.05). Neither IGF-I nor IGFBP-3 had an effect on P(450arom) expression or on the concentrations of its substrates. However, maximum expression of caspase 3 was detected in corpus luteum during the midluteal phase. In conclusion, these results indicate that IGF-I and IGFBP-3 act as regulatory peptides of the function of the human corpus luteum during the midluteal phase. This action may be direct or mediated by steroid production or by bcl-2-bax expression.

[Reference values of growth hormone binding protein (GHBP) for a normal pediatric population]. / Valores de referencia para proteína transportadora de hormona de crecimiento en una población pediátrica normal.

UNLABELLED: Circulating concentrations of the high affinity growth hormone binding protein (GHBP) may be a marker of GH receptor density as well as GH sensitivity. GOAL: To determine values of GHBP for a normal Chilean pediatric population. METHODS: We determined GHBP levels in 73 males and 73 females between 4 to 15.5 years and 4 to 16.8 years respectively, divided in 7 groups according to age and puberal status. RESULTS: The population was normally distributed in weight, height and body mass index (BMI). GHBP activity increased up to Tanner IV in males and Tanner III in females, and decreased slightly thereafter in Tanner V and IV respectively. There was a significant difference between GHBP levels of preschool children and those found in Tanner II to V in both sexes (p < 0.05). In addition, we found a positive correlation between GHBP vs weight, height and BMI (p < 0.001) in males and females. CONCLUSION: The availability of this methodology allows us to establish the normative value of GHBP in our population and provides useful information to interpret GH circulating levels in children with growth disorders.

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum.

The presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, mid-and late luteal phases was assessed by immunohisto-chemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.