Neuroendocrine Regulation of Metabolism.

Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei that comprise the hypothalamus, the arcuate nucleus is one of the major mediators in the regulation of food intake. The regulation of energy balance is also a key factor ensuring the maintenance of any species as a result of the dependence of reproduction on energy stores. Adequate levels of energy reserves are necessary for the proper functioning of the hypothalamic-pituitary-gonadal axis. This review discusses valuable data presented in the 2015 edition of the International Workshop of Neuroendocrinology concerning the fundamental nature of the hormonal regulation of the hypothalamus and the impact on energy balance and reproduction.

Matching of feedback inhibition with excitation ensures fidelity of information flow in the anterior piriform cortex.

Odor-evoked responses in mitral cells of the olfactory bulb are characterized by prolonged patterns of action potential (spike) activity. If downstream neurons are to respond to each spike in these patterns, the duration of the excitatory response to one spike should be limited, enabling cells to respond to subsequent spikes. To test for such mechanisms, we performed patch-clamp recordings in slices of the mouse anterior piriform cortex. Mitral cell axons in the lateral olfactory tract (LOT) were stimulated electrically at different intensities and with various frequency patterns to mimic changing input conditions that the piriform cortex likely encounters in vivo. We found with cell-attached measurements that superficial pyramidal (SP) cells in layer 2 consistently responded to LOT stimulation across conditions with a limited number (1-2) of spikes per stimulus pulse. The key synaptic feature accounting for the limited spike number appeared to be somatic inhibition derived from layer 3 fast-spiking cells. This inhibition tracked the timing of the first spike in SP cells across conditions, which naturally limited the spike number to 1-2. These response features to LOT stimulation were, moreover, not unique to SP cells, also occurring in a population of fluorescently labeled interneurons in glutamic acid decarboxylase 65-eGFP mice. That these different cortical cells respond to incoming inputs with 1-2 spikes per stimulus may be especially critical for relaying bulbar information contained in synchronized oscillations at beta (15-30Hz) or gamma (30-80Hz) frequencies.

The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides.

Glucosensing neurons in the hypothalamic arcuate nucleus (ARC) were studied using electrophysiological and immunocytochemical techniques in neonatal male Sprague-Dawley rats. We identified glucose-excited and -inhibited neurons, which increase and decrease, respectively, their action potential frequency (APF) as extracellular glucose levels increase throughout the physiological range. Glucose-inhibited neurons were found predominantly in the medial ARC, whereas glucose-excited neurons were found in the lateral ARC. ARC glucose-excited neurons in brain slices dose-dependently increased their APF and decreased their ATP-sensitive K+ channel (KATP channel) currents as extracellular glucose levels increased from 0.1 to 10 mmol/l. However, glucose sensitivity was greatest as extracellular glucose decreased to <2.5 mmol/l. The glucokinase inhibitor alloxan increases KATP single-channel currents in glucose-excited neurons in a manner similar to low glucose. Leptin did not alter the activity of ARC glucose-excited neurons. Although insulin did not affect ARC glucose-excited neurons in the presence of 2.5 mmol/l (steady-state) glucose, they were stimulated by insulin in the presence of 0.1 mmol/l glucose. Neuropeptide Y (NPY) inhibited and alpha-melanocyte-stimulating hormone stimulated ARC glucose-excited neurons. ARC glucose-excited neurons did not show pro-opiomelanocortin immunoreactivity. These data suggest that ARC glucose-excited neurons may serve an integrative role in the regulation of energy balance.

Hormonal control of pituitary prolactin-secreting tumors.

Prolactin secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Prolactinomas have been linked to estrogen exposure in humans and animals. However, the mechanism by which estrogen increases mitogenesis in lactotropes, as well as other estrogen responsive cells, is not well understood. Given the complex nature of steroid hormones and their wide array of actions, it seems plausible that there are multiple ways in which estrogen can exert its cell-transforming actions. Estrogen has a wide range of actions on cells depending on the cell type, receptor levels, and other factors present in the cell. A defect at any point could play a potential role in cell transformation. The source of such defects could be the result of any of a wide range of possibilities, including genetic predisposition, prolonged exposure to sufficient levels of the steroid hormone, or other insults to the cell which lead to altered responsiveness to estrogen in some way. This review discusses the recent advances that have been made in the area of understanding estrogen action in transformation of pituitary lactotropes.