Endocrine Abstracts

Uncoupling protein-2 (UCP2) has many postulated functions, including possible solute exchange and immunity within the neonatal lung. The effect of maternal nutrition during late gestation on UCP2 abundance in the ovine neonatal lung has not been determined.Twin-bearing ewes of similar age and body weight were individually housed from 110 days gestation. Six controls (C) were fed and consumed 100% of their energy requirements for maintenance and growth of...

Large databases facilitate the examination of those factors, which may determine response to treatment, potentially to develop prediction models. We have used KIMS (Pfizer's international metabolic database of GH-treated adults), to examine parameters that might predict clinical response to GH therapy in hypopituitary adults.Patients/methods: Patients with non-functioning pituitary adenoma on GH titrated to maintain serum IGF-I between minus 2 and 2 SDS,...

Aim: Differentiating idiopathic hypogonadotrophic hypogonadism from extreme maturational delay can be difficult, so most boys receive testosterone (T) replacement until the diagnosis becomes clear. Standard 3 month T therapy for maturational delay does not diminish adult stature, so we set out to determine whether T treatment of greater than 6 months duration would have an adverse effect on final height (FH) in boys with the eventual diagnosis of extreme maturational delay.</p...

OBJECTIVE: To quantify the extent of change in total body water (TBW) and nature of its relationship with changes in body composition, measured by direct methods, during physiological GH replacement in severely GHD adults.METHODS: Thirty (16 female, age range 17-65 years) severely GHD adults were studied. Patients with diabetes insipidus, cardiovascular or renal disease requiring diuretic therapy were excluded. Patients with other pituitary deficits had ...

Thyroid hormone (TH) is essential for fetal development and before 14 weeks maternal supply of TH is critical to the fetus. Subtle abnormalities of maternal thyroid status have been reported to affect neurodevelopment in childhood (1,2). To explore this further, we examined the relationship between maternal thyroid status and newborn measures of growth potential. A cohort of uncomplicated pregnant women (n=480) was recruited. At antenatal booking (mean gestation 13.05 weeks) m...

OBJECTIVE: To determine whether the quality of life improvement, observed with long-term physiological GH replacement, is correlated with favourable changes in body composition or total body water (TBW) measured by direct methods.METHODS: Thirty (16 female, age range 17-65 years) severely GHD adults were studied. Patients with diabetes insipidus, cardiovascular or renal disease requiring diuretic therapy were excluded. Patients with additional pituitary ...

Leptin is a hormone produced mainly from adipose tissue, which plays a major role in energy homeostasis. Its receptor Ob-R exists in five splice variants (Ob-Ra, b, c, d and e) with differing signal transduction abilities. The function of leptin and its receptor in development is not yet fully understood. This study determined the expression of leptin and its receptor in a number of fetal endocrine tissues.Tissue samples were obtained from 7 fetal sheep ...

The TRH test is used in the diagnosis of hypothalamic-pituitary (hp) disorders in children. It is unclear how often the result of this test is helpful. We have examined the results of TRH testing in 143 children investigated primarily for disordered growth. Children with hp axis tumours were excluded.The TSH response to TRH (5microg/kg iv) was defined as abnormal if the peak TSH was <5mU/L (pituitary), or if the peak TSH at 60 mins was higher than at ...

A number of single nucleotide polymorphisms (SNPs) have been identified in the GHRH receptor gene. Two of these SNPs, A57T and V225I, have been found to cause an increased cAMP response to GHRH stimulation in vitro, and it has been suggested that they may be associated with the abnormal biochemistry in patients with somatotroph adenomas. The objective of this study was to clarify the frequencies of these SNPs in the normal population and in subjects with short stature. The sub...

The vulnerability of early central nervous system (CNS) development to thyroid hormone (TH) deprivation has been highlighted by studies showing an association between maternal hypothyroxinemia during the first trimester and long-term neurodevelopmental delay in the offspring. The molecular mechanisms underlying this observation are, however, poorly understood. It is known that the actions of triiodothyronine (T3), the active TH metabolite, are primarily mediated by TRs, which ...

Aim - To assess the effect of transdermal testosterone (TT) on free testosterone concentrations in saliva and on short-term growth and bone turnover in boys with growth or pubertal delay.Method - Prospective, randomized, cross-over study over 26 weeks with 4 weeks of Run-In, 8 weeks of Treatment I (8 hours/12 hours), 4 weeks of Wash-Out, 8 weeks of Treatment II (8 hours/12 hours) and 4 weeks of final Wash-Out.Main Outcome Measures ...

Background: We have recently demonstrated that blood pressure (BP) in children was elevated in males compared to females in the post-pubertal period. We have also shown that the Y chromosome in associated to BP in adult men. Here we report on the effect of 2 polymorphisms on the Y chromosome on BP in male children studied longitudinally both in the pre- and post-pubertal periods.Methods: We genotyped for 2 SNPs (HindIII +/-; M9 C/G) on the Y chromosome n...

Hypopituitary patients receiving conventional hormonal therapy, excluding Growth Hormone, have an increased risk of vascular mortality. Significant endothelial dysfunction with impaired aortic distensibility has been demonstrated in these patients with some improvement in arterial stiffness after GH therapy. Inflammation is central in the pathophysiology of atherosclerosis and C-reactive protein is a validated marker for predicting cardiovascular risk.Fo...

T3, GH and IGF-1 are essential for skeletal development, growth and bone mineralisation. The major growth-promoting actions of GH occur in epiphyseal chondrocytes via direct effects on GH-receptor expressing cells and via a local paracrine pathway involving IGF-1. There is controversy regarding whether T3-actions in bone are direct or occur via regulation of GH secretion and action. We examined this in mice with a mutation (PV) targeted to either T3-receptor (TR) beta or alpha...

Pregnancy is associated with increased circulating growth hormone (GH), which is thought to originate from the placenta in humans, but from the pituitary in rats. In this study we investigated the changes in somatotroph and lactotroph populations, and quantified spontaneous and secretagogue-induced GH and prolactin (PRL) secretion during pregnancy in rats.Using electron microscopy and immunogold labelling, somatotroph and lactotroph populations were quan...

Gene arrays are a powerful tool to search for novel targets of drug action and disease-specific patterns of gene expression. GH has pleiotropic actions and thus a wide range of potential gene targets. Using an accessible tissue, namely peripheral blood mononuclear cells (PBMNCs), we have started to explore the use of gene arrays in the context of the in-vivo response to GH treatment.PBMNCs were obtained with consent and ethical permission from 2 prepuber...