Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 - Biomarkers for Skeletal Maturity Assessment in Class II Malocclusion

ABSTRACT Objective: To estimate the serum levels of non-radiologic biomarkers, Insulin-like Growth Factor-1 (IGF-1), and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) to potentially identify the pubertal growth spurt in skeletal Class II malocclusion subjects. Material and Methods: Eighty subjects (M-38, F-42) with skeletal Class II malocclusion in the age range of 11-18 years were recruited for the cross-sectional study. Human serum IGF-1 and IGFBP-3 were quantitatively assessed by enzyme-linked immunosorbent assay, and the cervical stage (CS) was evaluated from a lateral cephalogram. Results: Gender-wise comparison of the mean serum IGF-1 levels revealed that the initial peak was detected at CS2 in both genders, [males (87.87 ng/mL), females (78.49 ng/mL)]. However, there was a cognizable difference in the second peak of the mean serum IGF-1 levels between males (CS5, 68.58 ng/mL) and females (CS4, 74.63 ng/mL). Mean IGFBP-3 serum levels in male subjects were high in CS4 (47.24 ng/mL) with a further spike in CS6 (50.54 ng/mL), and in female subjects, it was found to be highest in CS3 (51.95 ng/mL) and then in CS5 (49.68 ng/mL). Conclusion: Mean IGF-1 levels exhibited both sexes' prepubertal and late pubertal spikes. Mean IGFBP-3 levels revealed a pubertal and a late pubertal spike in both sexes, with an earlier growth trend observed specific to females compared to males.

Short hairpin RNA targeting insulin-like growth factor binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats

ABSTRACT Purpose To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats. Materials and methods After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively. The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay. Results At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Conclusions Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.

Obesidad y riesgo del carcinoma mamario y endometrial: revisión / Obesity and risk of mammary and endometrial carcinoma: a review

Estudios estadísticos realizados en los Estados Unidos han demostrado que 1 de cada 8 mujeres desarrolla cáncer mamario. Se considera que el estradiol (E2) y la testosterona (T) juegan un importante papel, cuando circulan en el plasma como "biodisponibles". El ovario deja de sintetizar esteroides sexuales poco tiempo después del último ciclo menstrual, siendo la obesidad la principal responsable del aumento del E2 y la T en la menopausia sintetizados ambos a partir de la androstenodiona de origen suprarrenal, especialmente cuando el tejido graso se acumula en la zona visceral. La zona glúteo-femoral tiene muy poca actividad. En 1968, se describe una proteína que en inglés se denominó sex hormone binding globulin (SHBG) y en castellano, globulina ligadora de andrógenos y E2 (GLAE), que es la principal responsable del transporte de los esteroides sexuales en el plasma. La hiperinsulinemia es la principal responsable de la disminución de la GLAE, aumentando así el E2 y la T "biodisponibles". Los factores de crecimiento (IGF-I e IGF-II) son de gran actividad para promover la proliferación celular en la mayoría de los tejidos, con especial referencia en los cánceres de mama y de endometrio. Los péptidos circulan en el plasma unidos a seis proteínas ligadoras que regulan su actividad cuando actúan como mitógenos. Con respecto al antígeno prostático específico-que durante mucho tiempo se consideró exclusivo del hombre- hoy se lo puede determinar en la mujer, especialmente en la obesidad, en la hipertricosis y en el cáncer mamario y endometrial

Utilidad de la determinación del factor de crecimiento insulino-simil tipo I (IGF-I) y de su proteína ligante tipo 3 (IGFBP-3) en el diagnóstico de la deficiencia de hormona de crecimiento en niños / Usefulness of the measurement of insulin-like growth factor 1 (IGF-I) and IGF-1 binding protein-3 (IGFBP-3) for the diagnosis of growth hormone (GH) deficiency in children

Background: The diagnosis of GH deficiency (GHD) is based upon the results of GH stimulation tests, which have several drawbacks. Aim: To evaluate the usefulness of IGF-1 and IGFBP-3 for the diagnosis of GHD in prepuberal children. Material and methods: We measured IGF-I and IGFBP-3 in three group of subjects: I. GHD (n:24), height <-2SD for age (Z score, average ñ SD: -4.2 ñ 1.2), growth velocity 7 ng/ml (15.3 ñ 6.9 ng/ml), y III. Normal school children (n:35) with normal heights (-0.17 ñ 0.12 SD) were studied as controls. Results: IGF-1 and IGFBP-3 were significantly lower in GHD than in NGHD and controls (p <0.001), and in NGHD than in C (p <0.001). We defined the normal range of both proteins as ñ 2 SD of the mean of the control group. Using this criteria, IGF-I was low in 21/24 GHD, and in 12/32 NGHD. IGFBP-3 was low in 22/24 GHD, and in 6/32 NGHD. Only 1 GHD patient had both exams in the normal range, suggesting that he is probably NGHD. 4/32 of the NGHD had both exams below normal range, suggesting that they are probably GHD. Conclusions: IGF-1 and IGFBP-3 are important tools for the diagnosis of GHD

Factores de crecimiento insulino símiles: estructura, bioactividad y métodos de ensayo / Insulin-like growth factors: structure, bioativity and methods of assay

El sistema de los factores de crecimiento insulino-símiles (IGF) se halla involucrado en diferentes aspectos de la regulación celular y tisular, como así también en el desarrollo y el crecimiento corporal. Este sistema depende de la interacción entre ligandos (IGF-I, IGF-II), receptores (Tipo I, Tipo II), proteínas ligadoras o transportadoras (IGFBP-1 a -6), y proteasas específicas para las IGFBPs. La acción de los IGFs se encuentra regulada por diferentes factores y estímulos, tales como la hormona de crecimiento, que actúan a diversos niveles. El desarrollo de nuevos métodos para analizar los diferentes componentes del sistema de los IGFs ha aportado elementos adicionales para la evaluación, diagnóstico y seguimiento de pacientes con alteraciones del crecimiento