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First described in 1983, Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic disorder that leads to a spectrum of hypogonadal symptoms in adolescence. The responsible gene, DCAF17 located on chromosome 2q31.1, was discovered in 2008 and to date nine mutations have been reported in the literature. The aim of the study was to review WSS descriptively in the light of new case reports with focus on endocrine features. Phenotypic description of three patients (two females, one male) with WSS followed in the Endocrinology Department of the University Hospital of Nancy, France, and exhaustive review of the literature using the PUBMED database were performed. Of 72 patients from 29 families with documented WSS who were identified, 39 had undergone genetic testing. WSS was invariably associated with hypogonadism, decreased IGF1 and frontotemporal alopecia starting in childhood. In addition to this triad, some patients exhibited intellectual disabilities of varying severity (87 %), bilateral deafness (76 %), cervicofacial dystonia and limb pain (42 % of cases, rising to 89 % after 25 years) and diabetes (66 %, rising to 96 % after 25 years). The pathophysiology of WSS remains unclear.

The lateral hypothalamus (LH) has long been known as a homeostasis center of the brain that modulates feeding behavior, arousal and reward. The hypocretins (Hcrts, also called orexins) and melanin-concentrating hormone (MCH) are neuropeptides produced in two intermingled populations of a few thousand neurons in the LH. The Hcrts have a prominent role in regulating the stability of arousal, since Hcrt system deficiency leads to narcolepsy. MCH is an important modulator of energy balance, as MCH system deficiency in mice leads to leanness and increased metabolism. Recently, MCH has been proposed to modulate rapid eye movement sleep in rodents. In this review, we propose a working model of the cross-talk between Hcrt and MCH circuits that may provide an arousal balance system to regulate complex goal-oriented behaviors.

1. Melanin-concentrating hormone (MCH)-containing neurons within the lateral hypothalamus affect a broad spectrum of physiological and behavioral processes. The aim of this study was to examine a differentiation of rat MCH neurons dependent on their functionally related projections to the intermediolateral column (IML) of the spinal cord, the midbrain periaqueductal gray (PAG), and the brainstem locus coeruleus (LC). 2. A combination of retrograde fluorescent neuronal tracing and immunocytochemical identification revealed MCH neurons that project to IML, PAG, and LC. Subsequent to isolation of these single neurons by laser microdissection, multi-transcriptional profiling by means of real-time RT-PCR demonstrated different expression patterns between sympathetically projecting MCH neurons and those targeting the PAG or LC. 3. These results provide evidence for the existence of projection-dependent MCH neuronal subpopulations with functional differentiation in the context of controlling energy homeostasis, autonomic functioning, and arousal.

Experimental studies on the effects of stress on blood corticosteroid levels and the appearance of analgesia were carried out on rats anesthetized with Nembutai (4 mg/100 g). Stress, consisting of stimulation of the hind footpad with a current at 0.7 mA, produced parallel changes in plasma corticosteroid concentrations and the threshold of a pain response. Functional blockade of the hypophyseal-adrenocortical system, produced by systemic administration of hydrocortisone (15 mg/100 g) or by implantation of dexamethasone (200 micrograms) above the paraventricular nucleus of the hypothalamus, resulted in reductions in stress-induced analgesia. Dosage with naloxone (1 and 10 mg/kg) had no effect on the level of analgesia or corticosteroid concentrations. It is concluded that stress-induced analgesia not mediated by opioids is corticosteroid-dependent.

To study the behavior of the neuroendocrine polypeptide 7B2 in the presence of calcium, various fragments of this molecule were produced in Escherichia coli as fusion proteins to glutathione S-transferase (GST). Addition of millimolar concentrations of Ca2+ to purified preparations of hybrid molecules carrying the N-terminal segment of 7B2 induced precipitation in a manner dependent on protein and cation concentrations. This precipitation occurred at pH 7.5 but not at pH 5.2. It was augmented by 4 and 8 mM ATP, and reduced by 12 and 24 mM ATP. ADP had a similar but weaker effect. Calcium failed to cause precipitation of GST alone or of GST fused to the C-terminal peptide 7B2(156-186). However, when the latter protein was mixed with a GST protein carrying a short fragment of the N-terminal region of 7B2, both proteins were precipitated by calcium. Except for the pH dependence, the behavior of 7B2 fusion proteins in the presence of calcium and adenosine nucleotides are reminiscent of those exhibited by chromogranins and secretogranins, which, like 7B2, are acidic proteins found in the secretory granules of a variety of neuroendocrine cells. As suggested for other granins, this property may underlie the segregation of 7B2 fragments into secretory granules.

1. Several years ago, investigators described the effects of infantile handling on the development of hypothalamic-pituitary-adrenal (HPA) responses to stress in the rat. Rat pups exposed to brief periods of innocuous handling early in life showed reduced HPA responses to a wide variety of stressors, and the effect persists throughout the life of the animal. These effects are robust and provide an excellent model for understanding how early environmental stimuli, which are external to the organism, alter neural differentiation and, thus, neuroendocrine responsivity to stress. 2. This paper reviews the endocrine mechanisms affected by early handling and our current understanding of the neural transduction of environmental events and their effects at the level of the target neurons (in the hippocampus and frontal cortex). 3. In brief, handling serves to increase glucocorticoid receptor gene transcription, increasing sensitivity to glucocorticoid negative feedback regulation and, thus, altering the activity within hypothalamic corticotropin-releasing factor/vasopressin neurons. Together these changes serve to determine neuroendocrine responsivity to stress.