Endocrine Abstracts

Growth hormone (GH) and testosterone are both potent anabolic hormones, but it is not known whether they interact to positively regulate protein metabolism. To address this question, we have carried out two studies, in which we have investigated the impact of GH alone, testosterone alone and combined GH+testosterone, on whole body protein metabolism in hypopituitary men.In the first study, ten subjects received either GH (1.5 units daily) or GH+testosterone (250 milligrams...

The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder that is due to mutations of the dual zinc-finger transcription factor, GATA3. The C-terminal zinc finger (ZF2) is crucial for DNA binding, whilst the N-terminal finger (ZF1) stabilizes the DNA binding by ZF2 and interacts with other multi-type zinc finger proteins, referred to as Friends of GATA (FOG), which modulate GATA3 function. The majority of GATA3 mutations causing HDR ...

GATA3 is a member of the family of zinc finger transcription factors that recognise (A/T)GATA(A/G) motifs in DNA, and mutations that lead to haploinsufficiency cause the hypoparathyroidism, deafness and renal dysplasia syndrome (HDR). GATA3 has two zinc fingers, of which the carboxy-terminal finger (ZnF2) is essential for DNA binding, whereas the amino-terminal finger (ZnF1) stabilizes this binding and physically binds with other multi-type zinc finger proteins, which are refe...

Human securin, known also as pituitary tumor transforming gene (PTTG), has established oncogenic and cell regulatory functions. PTTG transforms cells in vitro, inhibits sister chromatid separation and regulates secretion of fibroblast growth factor-2 (FGF-2). FGF-2 is a key regulator of CNS development and PTTG/securin expression has previously been reported in murine fetal brain. We examined mRNA and protein expression of PTTG and FGF-2 in 35 first trimester (7-12 weeks) and ...

Pseudoexons resemble true exons by current bioinformatic criteria and may outnumber true exons by 10:1. They are, however, never spliced into mature mRNA. A point mutation in the GHR gene results in abnormal splicing of a pseudoexon, leading to Laron syndrome. The GHR pseudoexon lies between exons six and seven and the point mutation is adjacent to the pseudoexon 5' splice site.Our studies aimed to define the elements that normally prevent splicing of this pseudoexon.A...

The paired-like homeodomain transcriptional repressor HESX1 is implicated in forebrain and pituitary embryogenesis. A homozygous mutation (R160C) was identified in two siblings with septo-optic dysplasia (SOD), with consequent loss of DNA-binding. We have now identified a second homozygous mutation (I26T) within the highly conserved engrailed homology domain (eh-1) of HESX1 that is crucial for the repressor function of HESX1. We aimed to investigate the functional consequences...

IntroductionThe use of a specific questionnaire to assess quality of life(QoL) in adults with growth hormone deficiency (GHD) and its improvement after treatment requires further studies, in particular, their relationship to basal scores and Insulin like growth factor (IGF-1) values. We analysed our data to determine if the QoL as assessed by the QoL-AGHDA improved in adult GHD patients following growth hormone (GH) replacement.MethodsPatients referred with symptom...

It is now evident that ghrelin is more than just a growth hormone (GH) secretagogue; it plays an important role in energy homeostasis, increasing food intake and fat deposition, has cardiovascular effects, and inhibits cell proliferation.Ghrelin mRNA expression is widespread in human tissues, but little is known about the molecular mechanisms and signals that regulate gene expression at the transcriptional level. To address this we cloned and sequenced a 4kb region upstrea...

In patients with cirrhosis, levels of prolactin are often increased, which can be related to the disturbed metabolism of estrogens. According to recent results, prolactin presumably has its role as a factor for regeneration and the induction of growth-associated genes (e.g.: c-myc, c-fos, c-jun). To learn about the function of PRL in the pathogenesis of cirrhosis we focused on the conduct of the prolactin-receptor (PRL-R) during reconstruction from healthy liver parenchyma to ...

Wolffian duct (WD) development is believed to be testosterone dependent. However, patients with complete androgen insensitivity syndrome (CAIS) and a causative mutation in the androgen receptor (AR) still develop WDs. Exceptions to this observation are those patients with severe N-terminal mutations. We investigated the role of the AR in WD development in these patients.AR expression in genital skin fibroblasts (GSF) from eleven patients with CAIS was studied by Western hy...

Leptin, the 16 kDa product of the obese gene, and uncoupling proteins (UCP) are both involved in energy expenditure. Piglets have recently been shown to express UCP2, it has been speculated that the induction of UCP2 in adipose tissue by leptin may stimulate thermogenesis. The aim of this study was to investigate the effect of leptin administration on body temperature, leptin and UCP2 mRNA. Ten Meishan sows gave birth naturally at term and siblings were paired by birth weight ...

The diagnosis of GHD is based on GH stimulation tests. The test of choice is the ITT and a peak GH response of less than 9mU/L is considered diagnostic of GHD. Peak GH values of less than 20mU/L during an ITT are infrequently observed in healthy adults. In hypopituitary patients a peak GH values to the ITT of 9-20 mU/L likely represents a state of partial GHD, or GH insufficiency (GHI). To investigate if patients with GHI have similar features to GHD adults we assessed body co...

Leptin, 16 kDa polypeptide hormone is produced primarily, although not exclusively, by adipocytes. It has been proposed to play a role in neonatal growth and development. The objective of the study was to investigate the effect of chronic leptin administration on the growth performance and endocrine profile of neonatal pigs. Ten Meishan sows gave birth naturally at term and siblings were paired by birth weight and gender. Piglets were subsequently randomly allocated to either ...

Perinatal nutrition has marked effects on both the health and development of the newborn animal, especially in the case of the intra-uterine growth restricted (IUGR) foetus. IGF-1 and leptin play important roles in the regulation of growth and energy metabolism. The study aimed to examine whether prenatal nutrition influences the growth performance and endocrine profile of IUGR pigs. From day 85 of gestation, pregnant sows were allocated to the standard diet (S: n=4) or the S ...

InroductionDue to persistent qualitative abnormalities in GH secretion following treatment, it is extremely difficult to diagnose GHD in treated acromegalic patients. We aimed to study the response of successfully treated acromegalic patients to the combined growth hormone releasing hormone and arginine test and compare it with the insulin tolerance test.Patients and MethodsTwelve acromegalic patients, in whom mean serum GH level off medical treatment was below 5mU...

Continuation of GH at final height in hypopituitary adolescents with severe GH-deficiency results in accrual of bone mass over 12 months. We report body composition and BMD in 7 of these patients who discontinued GH but continued to have observations over 24 months. Five males and 2 females were included (17.4plus/minus0.3, years, meanplus/minusSE), in this Ethics Commitee approved study. All had severe GH-deficiency with multiple pituitary hormone deficits on appropriate repl...