Reduced pericellular sensitivity to IGF-I in fibroblasts from girls with Turner syndrome: a mechanism to impair clinical responses to GH.

Girls with Turner syndrome (TS) are treated with supraphysiological doses of growth hormone (GH) to improve final height; however in some girls, the growth response can be poor. This may reflect aberrations in GH and/or IGF-I actions at the cellular level, and thus this study compared the response of skin fibroblasts from normal children (n = 5) and girls with TS (n = 8) to GH, IGF-I, or a combination, by assessing the IGF binding protein (IGFBP) profile of conditioned medium harvested over 7 d. The two cell types had a comparable IGFBP profile; IGFBP-3 and IGFBP-4 were the most abundant species.

The effect of different patterns of growth hormone administration on the IGF axis and somatic and skeletal growth of the dwarf rat.

Normal childhood growth is determined by ultradian and infradian variations in GH secretion, yet GH treatment of children with short stature is restricted to daily fixed doses. We have used GH-deficient dwarf rats to determine whether variable GH dose regimens promote growth more effectively than fixed doses. Animals were treated with saline or 4.

A pilot study to evaluate gene expression profiles in peripheral blood mononuclear cells (PBMCs) from children with GH deficiency and Turner syndrome in response to GH treatment.

Response to GH treatment is variable and dependent on diagnosis and dose. We used a pharmacogenomic approach to assess whether this variability is reflected in patterns of GH-induced gene expression in peripheral blood mononuclear cells (PBMCs) taken from three children with GH deficiency (GHD) and three girls with Turner syndrome (TS). Analysis of the response to GH treatment revealed that in GHD, 15 probe sets (11 genes) showed a fold change > +/- 1.

The relationship between nocturnal urinary leptin and gonadotrophins as children progress towards puberty.

Background/aims: Leptin is necessary for normal human pubertal development but its exact role in the period leading up to the onset of puberty has not been defined. This study has assessed the relationship between leptin and gonadotrophin secretion over time as children progress into puberty.

Subjects And Methods: Twenty children (13 boys and 7 girls) judged to be close to the initiation of puberty were recruited.

The contributions of plasma IGF-I, IGFBP-3 and leptin to growth in extremely premature infants during the first two years.

We determined the contributions of IGF-I, IGFBP-3 and leptin to growth in extremely premature infants over the first two years. Weight (Wt), crown-to heel length (CHL), plasma IGF-I, IGFBP-3 and leptin were measured in infants (gestation 24-33 wk) at birth (n = 54), expected date of delivery (EDD) and 6, 12 and 24 mo post-EDD (n = 29). Area under the curve (AUC) for hormone levels was calculated over 4 periods: birth-EDD, EDD-200 d, EDD-350 d and EDD-700 d.

Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms.

Objectives: Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress, often with dominant inheritance. It is likely that one or more genes will be associated with CDGP. Possible candidates are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links nutritional status to pubertal development.

Variability in anterior pituitary size within members of a family with GH deficiency due to a new splice mutation in the GHRH receptor gene.

Objective: Mutations in the GHRH receptor (GHRHR) gene (GHRHR) cause autosomal recessive isolated GH deficiency (IGHD), and are usually associated with anterior pituitary hypoplasia (APH) (defined as pituitary height more than 2 SDS below normal). We searched for GHRHR mutations and studied pituitary morphology in three prepubertal sibs with severe IGHD, who were born from consanguineous parents.

Design: We sequenced the 13 exons and the intron-exon boundaries of the GHRHR of the index patient.

A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency.

Objective: Mutations in the GH-releasing hormone (GHRH) receptor (GHRHR) gene (GHRHR) cause autosomal recessive familial isolated GH deficiency (IGHD). We searched for GHRHR mutations in two siblings with IGHD type IB and a history of parental consanguinity.

Design: We analyzed peripheral genomic DNA of an index patient.

Leptin measurement in urine in children and its relationship to other growth peptides in serum and urine.

Objective: Leptin has been implicated in the interaction between nutrition, energy balance and sexual maturation in humans. A non-invasive method of measuring leptin would greatly facilitate longitudinal studies of changes in leptin in normal children. The aim of this study was to evaluate the use of urinary leptin as a surrogate for serum leptin measurements.

GH and epidermal growth factor signaling in normal and Laron syndrome fibroblasts.

We have investigated and compared GH and epidermal growth factor (EGF) signaling in primary human skin fibroblasts from normal subjects and subjects with GH-binding protein-positive Laron syndrome (LS). In normal human fibroblasts, GH and EGF activate the tyrosine phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT5b; in LS fibroblasts, EGF does, but GH does not. GH also activates the tyrosine phosphorylation of Janus kinase (JAK)2 in normal, but not LS, fibroblasts.