Resch JM, Maunze B, Gerhardt AK, Magnuson SK, Phillips KA, Choi S. Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism. Am J Physiol Endocrinol Metab 305: E1452-E1463, 2013. First published October 22, 2013; doi:10.1152/ajpendo.00293.2013.-Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei, suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites; however, meal pattern analysis revealed that only injections into the PVN produced significant reductions in meal size, duration, and total time spent eating. PACAP-mediated hypophagia in both the PVN and VMN was abolished by PAC1R antagonism, whereas pretreatment with a VPACR antagonist had no effect. PACAP injections into the VMN produced unique changes in metabolic parameters, including significant increases in core body temperature and spontaneous locomotor activity that was PAC1R dependent whereas, PVN injections of PACAP had no effect. Finally, PACAP-containing afferents were identified using the neuronal tracer cholera toxin subunit B (CTB) injected unilaterally into the PVN or VMN. CTB signal from PVN injections was colocalized with PACAP mRNA in the medial anterior bed nucleus of the stria terminalis, VMN, and lateral parabrachial nucleus (LPB), whereas CTB signal from VMN injections was highly colocalized with PACAP mRNA in the medial amygdala and LPB. These brain regions are known to influence energy homeostasis perhaps, in part, through PACAP projections to the PVN and VMN.feeding; activity; temperature; hypothalamus; rat PITUITARY ADENYLATE CYCLASE-ACTIVATING polypeptide (PACAP) is a key regulator of several hypothalamic systems, including stress (1), osmoregulation (17), thermoregulation (21), and body weight (27). PACAP was first discovered to influence energy homeostasis through inhibition of feeding in mice following a single intracerebroventricular (icv) injection of the peptide (39). These results combined with reports of dietspecific alterations of PACAP mRNA expression in the hypothalamic ventromedial nuclei (VMN) suggest that PACAP is responsive to nutritional status and directly tied to metabolic systems linked to energy expenditure (27,40). In addition to reducing food intake, icv administration of PACAP modulates autonomic nerve activity (55) as well as hepatic glucose production (60). As a ligand, PACAP binds to three different G protein-coupled receptors, the PAC1 receptor (PAC1R), and the receptors originally discovered as targets...

We report a 26-year-old woman presented at the day of admission in the I.C.U. with increased perspiration, plethora and distinct tetany of both legs. Particularly unusual was an exophthalmus on both sides, a rectal temperature of 38.3 degrees Celsius and a blood pressure of high level (180/110 mmHg). Laboratory findings were a low serum calcium concentration of 2.86 mval/l, a hyperphosphataemia (5.0 mg/dl), free thyroxine of 31.7 pmol/l, TSH basal of < 0.01 U/ml and positive MAK and TRAK. Serum parathormone concentration was excessively high: 766 ng/l (12-72). Ultrasound of the thyroid gland revealed a normal size with a volume of 10.4 ml; the echosonic state was not typical for Graves' disease. The initial treatment consisted of high dose thiamazole and hydrocortisone intravenous, calciumcarbonate and propranolol per os. After acute situation the treatment continued with thyreostatics, calcitriol and calciumcarbonate. The symptoms at the day of admission (tetany) disappeared within 2 days; only local paraesthesia of fingers persisted longer. Normalization of thyroid parameters was reached after 11 days; the serum calcium concentration persisted on an increasing but still lower level than standard (3.8 mval/l). During substitution parathormone decreased to 443 ng/l. What is unusual about this case is the combined appearance of autoimmunethyreoiditis (Graves' disease) and pseudohypoparathyroidism.