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Plagemann A, Davidowa H, Harder T, Dudenhausen J. Developmental programming of the hypothalamus: a matter of insulin. A comment on: Horvath, T. L., Bruning, J. C.: Developmental programming of the hypothalamus: a matter of fat. Nat. Med. (2006) 12: 52-53. Neuro Endocrinol Lett. 2006 Apr; 27(1-2): 70-72
OBJECTIVES: Cytochrome oxidase activity has been determined in the adrenal glands of thioacetamide (TAA)-cirrhotic rats.
MATERIAL AND METHODS: Two groups of animals (Control group; n=10 and TAA group; n=11) of three months evolution were used to study the cytochrome oxidase activity in the suprarenal cortex (glomerular, fascicular and reticular layers) and medulla. TAA was administered orally and cytochrome oxidase (COX) activity was assayed by an immunohistochemical technique.
RESULTS: In TAA-cirrhotic rats, COX activity increases in the cortex fascicular layer (221 +/- 1.79 vs 181.9 +/- 2.75; p<0.001) as well as in the medulla (146.6 +/- 1.72 vs 129 +/- 3.09; p<0.001).
CONCLUSION: These results make it possible to consider the existence of hypothalamic-pituitary-adrenal-axis and adrenomedullary sympathetic system hyperactivity, both peripheral limbs of the stress system, in this experimental model of cirrhosis....
Méndez-López M, Méndez M, López L, Aller M, González-Pardo H, Nava M, Sánchez-Patán F, Arias J, Arias J. Increased cytochrome oxidase activity in adrenal glands of thioacetamide-cirrhotic rats. Neuro Endocrinol Lett. 2005 Dec; 26(6): 719-723
OBJECTIVES: PPAR-gamma agonists are able to inhibit pituitary tumour development and tumoral hormonal secretion in rodents both in vitro and in vivo. Their use for treatment of Cushing Disease (CD) has been suggested but the clinical experience with the two PPAR-gamma agonists commercially available (rosiglitazone and pioglitazone) was not impressive. Short-time treatment has been proposed to be the cause of unsuccessful results on CD in humans. We report here the effect on early-morning plasma cortisol levels of a long-time treatment with rosiglitazone at the highest approved dose.
METHODS: Because PPAR-gamma receptors are located in normal corticotroph cells we tested in a placebo-controlled study the influence of rosiglitazone on cortisol secretion. The study enrolled 30 newly diagnosed type 2 patients which were assigned to receive either rosiglitazone (8 mg/day) or placebo. Plasma morning cortisol (8.00 a.m.) was measured at the baseline and at the end of the study.
RESULTS: Rosiglitazone vs placebo did not modify the early morning plasma levels of cortisol (13 microg/dl [3-21] vs 11 microg/dl [7-23] [median and range]) after 26 weeks of treatment.
CONCLUSION: The discrepancy between in vitro and animal data on one side and clinical data on the other side warrant further investigations into the mechanisms of action of PPAR-gamma agonists on ACTH secretion before other clinical studies will be conducted....
Catrina S, Virtanen K, Hällsten K, Lönnqvist F, Nuutila P, Brismar K. Effect of rosiglitazone on early-morning plasma cortisol levels. Neuro Endocrinol Lett. 2005 Dec; 26(6): 757-758
OBJECTIVES: Hypothalamic neurons of rats overweight due to early postnatal overfeeding (SL) differ from those of control rats in their responses to feeding relevant hormones like leptin or insulin. The question arose whether prolactin and prolactin-releasing peptide (PrRP) express also differential action in SL rats. These peptides are described to have an effect on food intake and body weight regulation. Prolactin is co-synthesized in lateral hypothalamic neurons together with orexins that were also analyzed in this study.
METHODS: Single unit activity was extracellularly recorded in brain slices from adult control rats (CL) and from rats previously raised in small litters (SL). The action of the peptides on the firing rates was evaluated in the medial parvicellular part of the paraventricular nucleus (PaMP) and the medial arcuate nucleus (ArcM).
RESULTS: In control rats, PrRP significantly activated PaMP neurons, whereas prolactin and orexin-A induced also inhibition. In SL rats, there was a significantly different effect of orexin-B on PaMP neurons: the main effect changed from activation in controls to inhibition. ArcM neurons of both control and SL rats were mainly excited by prolactin and orexins.
CONCLUSION: Changes acquired during early development of neuronal responses to feeding relevant peptides are not a general non-specific mechanism of neurochemical plasticity, but concern specific hypothalamic nuclei and/ or hormones and neuropeptides. The increase in inhibition by orexin-B of hypothalamic paraventricular neurons could in vivo contribute to the neonatally acquired disposition towards persistingly increased food intake and reduced energy expenditure of overweight SL rats....
Davidowa H, Plagemann A. Action of prolactin, prolactin-releasing peptide and orexins on hypothalamic neurons of adult, early postnatally overfed rats. Neuro Endocrinol Lett. 2005 Oct; 26(5): 453-458
OBJECTIVE: The aim of this study was the detection and location of long form leptin receptor (OB-Rb) in different area of hypothalamus and pituitary in the pig during early pregnancy.
SETTINGS AND DESIGN: Expression of OB-Rb was examined by RT-PCR in the different area of hypothalamus: medial basal hypothalamus (MBH), preoptic area (POA), stalk median eminence (SME), as well as pituitary: the anterior (AP) and posterior (NP) lobe collected from gilts at days 14-16 (n=4) and 30-32 (n=4) of pregnancy.
RESULTS: The results showed that OB-Rb mRNA was expressed in the hypothalamus (MBH, POA and SME), pituitary (AP, NP) and adipose tissue in the pig during early pregnancy (at days 14-16 and 30-32).
CONCLUSION: These findings support the idea that leptin might play a role in the regulation of the hypothalamic-pituitary axis activity, and consequently in the control of pregnancy during critical period of embryo implantation in the pig....
Siawrys G, Przala J, Kaminski T, Smolinska N, Gajewska A, Kochman K, Skowronski M, Staszkiewicz J. Long form leptin receptor mRNA expression in the hypothalamus and pituitary during early pregnancy in the pig. Neuro Endocrinol Lett. 2005 Aug; 26(4): 305-309
INTRODUCTION: The labor at term finishes normal pregnancy. Both labor at term and first trimester spontaneous abortion are connected with increasing cytotoxic immune response within decidua. Th1 cytokines including IL-2 and INF-gamma are able to exert an effect on HPA axis and result in ACTH secretion. Oxytocinase serum level during pregnancy rises with the fetal development and arrest of oxytocinase serum growth might indicate the its development impairment, what might result in spontaneous abortion.
MATERIAL AND METHODS: The study group consisted of 27 patients with clinical symptoms of missed abortion. A control group consisted of 89 pregnant women, who were successfully treated because of infertility. Immunoassay was used to measure ACTH plasma concentration. Oxytocinase plasma activity was established using l-cystine-di-beta-naphthylamide as a substrate.
RESULTS: In the present study, significant increase in ACTH plasma concentration was observed during first trimester of spontaneous abortion. These patients were not characterized by significant increase of oxytocinase plasma level.
CONCLUSIONS: The observed ACTH rise during spontaneous abortion might be also related to the alterations at the maternal-fetal interface and the response of HPA axis to the growing cytotoxic activity....
Klimek M, Wicherek L, Popiela T, Skotniczny K, Tomaszewska B. Changes of maternal ACTH and oxytocinase plasma concentrations during the first trimester of spontaneous abortion. Neuro Endocrinol Lett. 2005 Aug; 26(4): 342-346
OBJECTIVES: Present experiments were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on vasopressin (AVP) secretion from the rat hypothalamo-neurohypophysial (HN) system in vitro.
RESULTS: The results showed that both substance P and highly selective tachykinin NK-1 receptor agonist, i.e., [Sar9,Met(O2)11]-Substance P, enhanced significantly AVP secretion, while the NK-1 receptor antagonist (Tyr6,D-Phe7,D-His9)-Substance P (6-11)--sendide--was found to antagonize the substance P-induced hormone release from isolated rat HN system (all peptides at the concentration of 10(-7) M/L). The NK-2 receptor selective agonist (beta-Ala8)-Neurokinin A (4-10) was essentially inactive in modifying AVP release from the rat HN system in vitro, while neurokinin A (the natural ligand for this tachykinin receptor) was found to stimulate the AVP release; this effect of neurokinin A has been diminished by the NK-2 receptor antagonist (Tyr5,D-Trp(6,8,9),Lys-NH2(10))-Neurokinin A (4-10).
CONCLUSION: The present data indicate a role for tachykinin NK-1 (and possibly for NK-2) receptors in tachykinin-mediated stimulation of AVP secretion from the rat HN system in vitro....
Juszczak M. Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists. Neuro Endocrinol Lett. 2005 Aug; 26(4): 367-372
OBJECTIVES: The study investigated the role of prolactin (PRL) in modulating STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO) nucleus of male rats.
METHODS: Evidence of expression of STAT5 in the SO nucleus was investigated by immunocytochemical methods. Effect of blocking prolactin receptors on STAT 5 expression was investigated by Western blotting following transfection of SO neurones with a dominant negative mutant form of the PRL receptor. Prolactin-induced changes in electrical activity were investigated by extracellular recording in hypothalamic slices.
RESULTS: A high proportion of SO neurones in male rats expressed immunoreactive STAT5. Levels of activated STAT5 within the SO nucleus of PRL-treated rats was reduced following transfection with a dominant negative mutant form of the PRL receptor, as compared to rats transfected with wild type PRL receptor. Electrophysiological recordings from the SO nucleus in horizontal brain slices showed that approximately 25% of neurones were responsive to PRL, with both inhibitory and excitatory effects being observed. Cells displaying PRL responses included pharmacologically-identified oxytocinergic neurones.
CONCLUSIONS: Collectively, the results suggest that central PRL targets neurones of the SO nucleus, influencing both activation of the JAK-STAT signalling pathway and neuronal excitability. Whilst the functional significance of this interaction remains to be established, it might be important in co-ordinating oxytocin secretion with physiological events associated with changes in plasma PRL, or in mediating a feedback loop in the oxytocinergic regulation of lactotrophs....
Townsend J, Cave B, Norman M, Flynn A, Uney J, Tortonese D, Wakerley J. Effects of prolactin on hypothalamic supraoptic neurones: evidence for modulation of STAT5 expression and electrical activity. Neuro Endocrinol Lett. 2005 Apr; 26(2): 125-130