Programming of the Hypothalamus-Pituitary-Adrenal Axis by Very Preterm Birth.

BACKGROUND: Many very preterm (i.e., <32 weeks of gestation) newborns fail to mount an adequate adrenocortical response to stress or illness, termed relative adrenal insufficiency. Conversely, later in life these infants show features of increased glucocorticoid bioactivity, such as abdominal adiposity, insulin resistance, raised blood pressure, shorter stature and internalizing problem behavior. SUMMARY: Studies suggested that very preterm newborns have impairments along multiple levels of the hypothalamus-pituitary-adrenal (HPA) axis. Among the impairment were defects in: (1) the pituitary responsiveness to exogenous corticotropin-releasing hormone, (2) 11ß-hydroxylase activity, and (3) the interconversion between cortisol and inert cortisone. There is some evidence suggesting that later in life these infants have an increased basal secretion rate of cortisol and adrenal hyperandrogenism. However, the response to acute (psychosocial) stress was blunted rather than enhanced in them. The mechanisms explaining this switch in HPA axis activity are complex and not yet fully understood. Key Messages: Very preterm newborns have several impairments along the HPA axis that could impede an adequate adrenocortical response to stress or illness. Later in life, these infants are predisposed to increased HPA axis activity, which could partially explain their phenotype.

Assessment of thyroid endocrine system impairment and oxidative stress mediated by cobalt ferrite (CoFe2 O4 ) nanoparticles in zebrafish larvae.

Fascinating super paramagnetic uniqueness of iron oxide particles at nano-scale level make them extremely useful in the state of the art therapies, equipments, and techniques. Cobalt ferrite (CoFe2 O4 ) magnetic nanoparticles (MNPs) are extensively used in nano-based medicine and electronics, results in extensive discharge and accumulation into the environment. However, very limited information is available for their endocrine disrupting potential in aquatic organisms. In this study, the thyroid endocrine disrupting ability of CoFe2 O4 NPs in Zebrafish larvae for 168-h post fertilization (hpf) was evaluated. The results showed the elevated amounts of T4 and T3 hormones by malformation of hypothalamus pituitary axis in zebrafish larvae. These elevated levels of whole body THs leads to delayed hatching, head and eye malformation, arrested development, and alterations in metabolism. The influence of THs disruption on ROS production and change in activities of catalase (CAT), mu-glutathione s-transferase (mu-GST), and acid phosphatase (AP) were also studied. The production of significantly higher amounts of in vivo generation of ROS leads to membrane damage and oxidative stress. Presences of NPs and NPs agglomerates/aggregates were also the contributing factors in mechanical damaging the membranes and physiological structure of thyroid axis. The increased activities of CAT, mu-GST, and AP confirmed the increased oxidative stress, possible DNA, and metabolic alterations, respectively. The excessive production of in vivo ROS leads to severe apoptosis in head, eye, and heart region confirming that malformation leads to malfunctioning of hypothalamus pituitary axis. ROS-induced oxidative DNA damage by formation of 8-OHdG DNA adducts elaborates the genotoxicity potential of CoFe2 O4 NPs. This study will help us to better understand the risk and assessment of endocrine disrupting potential of nanoparticles. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2068-2080, 2016.

Childhood maltreatment increases the risk for visceral obesity.

OBJECTIVE: The reports regarding the associations between childhood maltreatment (CM) and body fat composition remain heterogeneous in humans although they are indicated in preclinical studies. In addition, the effects of CM subtypes on different types of body fat are unclear. Thus, in this study, the associations between CM and its subtypes with body fat were determined and the potential pathways were explored. METHODS: The participants were assessed for a history of CM by the Childhood Trauma Questionnaire and were divided into the CM group (with CM exposures) and non-CM group (without CM exposures). Body composition was measured by dual-energy X-ray absorptiometry. Salivary and blood samples were provided by the subjects. RESULTS: Compared with the non-CM group, subjects with a history of CM had greater visceral fat mass (1,136 ± 160 vs. 836 ± 116 g, P < 0.05) but not total body fat, android fat, body mass index, or waist-to-hip ratio. In addition, subjects with CM had a blunted cortisol awakening response and elevated inflammatory factors. Correlation analysis indicated that CM subtypes had differential effects on visceral adiposity and cortisol awakening response. CONCLUSIONS: It is suggested by our results that CM exposure is linked with increased visceral fat deposition, and the perturbation of the hypothalamic-pituitary-adrenal axis activity and activation of the immune system may be two potential pathways through which this relationship is explained.

High proportion of pituitary abnormalities and other congenital defects in children with congenital nasal pyriform aperture stenosis.

We aimed to determine the occurrence of pituitary dysfunction and additional malformations in patients with congenital nasal pyriform aperture stenosis (CNPAS) and to predict which patients are at risk of pituitary dysfunction. Among the 40 studied patients, hypothalamo-pituitary (HP) axis abnormalities were found in 16 patients (40%), with endocrine dysfunction (n = 9) and/or abnormal HP MRI findings (n = 15). A normal HP axis on MRI was highly predictive of normal endocrine function. Of the 40 patients, 31 had additional abnormalities in the cranio-facial area (n = 26), the brain (n = 12), the vertebrae (n = 5), the limbs (n = 4), the heart (n = 7) and the kidney (n = 3). Six patients had syndromic associations: VACTERL (n = 4), CHARGE (n = 1) and RHYNS (n = 1) syndromes. Craniofacial and brain malformations were more common in patients with HP axis abnormalities than in patients with normal HP axis. Familial history of midline defects and/or consanguinity were found in 30% of patients. In conclusion, HP axis abnormalities are frequent in patients with CNPAS and justify MRI of the brain early in life and clinical evaluation to screen for patients with pituitary insufficiency. CNPAS may be a genetically heterogeneous condition with a large phenotypic variability that shares common etiological mechanisms with the various forms of the holoprosencephaly phenotype.

Adrenal hypoplasia and pituitary agenesis in a normocephalic infant, with a review of the literature.

A case of adrenal hypoplasia and pituitary agenesis in a normocephalic female infant is described. Twenty-eight other cases from the world literature were reviewed. There were 18 females and 11 males. More than one affected infant was described in five families, suggesting autosomal recessive inheritance. The mode of presentation, subsequent course, pathology and possible pathogenesis are discussed.

Growth retardation due to idiopathic growth hormone deficiencies: MR findings in 24 patients.

In this study we evaluated the pituitary-hypothalamic abnormalities of "idiopathic growth hormone (GH) deficiency" as demonstrated by MR imaging. Twenty-four patients were examined with a 1.5-T unit using spin echo T-1 weighted images. The patients were divided into two groups according to MR findings: those with ectopic posterior pituitary glands (12 patients), and those with normal posterior pituitary glands (12 patients). Ten patients in the former group and four in the latter group had small anterior pituitary glands. All patients in the former group but only four in the latter group had severe GH deficiencies. Multiple hormone deficiencies were found in eight patients in the former group, but in only two in the latter group. Among the 12 patients with posterior pituitary ectopia, 11 were males, 10 had been born by breech delivery, and four had a history of asphyxia. It is speculated that perinatal abnormalities can cause posterior pituitary ectopia and that there is a close correlation between breech delivery and the male disadvantage of posterior pituitary ectopia. Half of our patients with "idiopathic GH deficiency" had ectopic posterior pituitaries. GH deficiency with posterior pituitary ectopia should no longer be considered idiopathic because organic lesions can now be identified during life.

DAX1 and its network partners: exploring complexity in development.

DAX1 encoded by NR0B1, when mutated, is responsible for X-linked adrenal hypoplasia congenita (AHC). AHC is due to failure of the adrenal cortex to develop normally and is fatal if untreated. When duplicated, this gene is associated with an XY sex-reversed phenotype. DAX1 expression is present during development of the steroidogenic hypothalamic-pituitary-adrenal-gonadal (HPAG) axis and persists into adult life. Despite recognition of the crucial role for DAX1, its function remains largely undefined. The phenotypes of patients and animal models are complex and not always in agreement. Investigations using cell lines have proved difficult to interpret, possibly reflecting cell line choices and their limited characterization. We will review the efforts of our group and others to identify appropriate cell lines for optimizing ex vivo analysis of NR0B1 function throughout development. We will examine the role of DAX1 and its network partners in development of the hypothalamic-pituitary-adrenal/gonadal axis (HPAG) using a variety of different types of investigations, including those in model organisms. This network analysis will help us to understand normal and abnormal development of the HPAG. In addition, these studies permit identification of candidate genes for human inborn errors of HPAG development.