scholarly journals Hindbrain Catecholamine Neurons Modulate the Growth Hormone But Not the Feeding Response to Ghrelin

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3237-3246 ◽  
Author(s):  
Alan J. Emanuel ◽  
Sue Ritter
Keyword(s):  
Feeding Response ◽  
Gh Treatment ◽  
Anatomical Distribution ◽  
Adrenergic Neurons ◽  
Gh Secretion ◽  
Cell Groups ◽  
Baseline Levels ◽  
Fos Expression ◽  
Catecholamine Neurons

The gastrointestinal peptide, ghrelin, elicits feeding and secretion when administered systemically or centrally. Previous studies have suggested that hypothalamic projections of hindbrain catecholamine neurons are involved in both of these actions of ghrelin. The purpose of this study was to further assess the role of hindbrain catecholamine neurons in ghrelin-induced feeding and GH secretion and to determine the anatomical distribution of the catecholamine neurons involved. We lesioned noradrenergic and adrenergic neurons that innervate the medial hypothalamus by microinjecting the retrogradely transported immunotoxin, saporin (SAP) conjugated to antidopamine-β-hydroxylase (DSAP) into the paraventricular nucleus of the hypothalamus. Controls were injected with unconjugated SAP. We found that the DSAP lesion did not impair the feeding response to central or peripheral ghrelin administration, indicating that these neurons are not required for ghrelin’s orexigenic effect. However, the GH response to ghrelin was prolonged significantly in DSAP-lesioned rats. We also found that expression of Fos, an indicator of neuronal activation, was significantly enhanced over baseline levels in A1, A1/C1, C1, and A5 cell groups after ghrelin treatment and in A1, A1/C1, and A5 cell groups after GH treatment. The similar pattern of Fos expression in catecholamine cell groups after GH and ghrelin and the prolonged GH secretion in response to ghrelin in DSAP rats together suggest that activation of hindbrain catecholamine neurons by ghrelin or GH could be a component of a negative feedback response controlling GH levels.

scholarly journals Activation of catecholamine neurons in the ventral medulla reduces CCK-induced hypophagia and c-Fos activation in dorsal medullary catecholamine neurons

2018 ◽  
Vol 315 (3) ◽  
pp. R442-R452
Author(s):  
Ai-Jun Li ◽  
Qing Wang ◽  
Sue Ritter
Keyword(s):  
Food Intake ◽  
Ventrolateral Medulla ◽  
Designer Drug ◽  
Cell Group ◽  
Cell Groups ◽  
Increase Food Intake ◽  
Threatening Condition ◽  
Metabolic Conditions ◽  
Fos Expression ◽  
Catecholamine Neurons

Catecholamine (CA) neurons within the A1 and C1 cell groups in the ventrolateral medulla (VLM) potently increase food intake when activated by glucose deficit. In contrast, CA neurons in the A2 cell group of the dorsomedial medulla are required for reduction of food intake by cholecystokinin (CCK), a peptide that promotes satiation. Thus dorsal and ventral medullary CA neurons are activated by divergent metabolic conditions and mediate opposing behavioral responses. Acute glucose deficit is a life-threatening condition, and increased feeding is a key response that facilitates survival of this emergency. Thus, during glucose deficit, responses to satiation signals, like CCK, must be suppressed to ensure glucorestoration. Here we test the hypothesis that activation of VLM CA neurons inhibits dorsomedial CA neurons that participate in satiation. We found that glucose deficit produced by the antiglycolytic glucose analog, 2-deoxy-d-glucose, attenuated reduction of food intake by CCK. Moreover, glucose deficit increased c-Fos expression by A1 and C1 neurons while reducing CCK-induced c-Fos expression in A2 neurons. We also selectively activated A1/C1 neurons in TH-Cre+ transgenic rats in which A1/C1 neurons were transfected with a Cre-dependent designer receptor exclusively activated by a designer drug (DREADD). Selective activation of A1/C1 neurons using the DREADD agonist, clozapine- N-oxide, attenuated reduction of food intake by CCK and prevented CCK-induced c-Fos expression in A2 CA neurons, even under normoglycemic conditions. Results support the hypothesis that activation of ventral CA neurons attenuates satiety by inhibiting dorsal medullary A2 CA neurons. This mechanism may ensure that satiation does not terminate feeding before restoration of normoglycemia.

ANDROST-5-ENE-3β,17β-DIOL IN OVARY OF POST-MENOPAUSAL HYPEROESTROGENIC WOMEN

1968 ◽  
Vol 58 (3) ◽  
pp. 364-376 ◽  
Author(s):  
S. Pesonen ◽  
M. Ikonen ◽  
B-J. Procopé ◽  
A. Saure
Keyword(s):  
Ovarian Tissue ◽  
Cortical Layer ◽  
Vaginal Smears ◽  
Incubation Experiments ◽  
Cell Groups ◽  
Post Menopause ◽  
Reducing Activity ◽  
Post Menopausal ◽  
One Year

ABSTRACT The ovaries of ten patients, at least one year after the post-menopause, were incubated with two Δ5-C19-steroids and also studied histochemically. All these patients had post-menopausal uterine bleeding and increased oestrogen excretion of the urine. The urinary estimations of gonadotrophins, 17-KS, 17-OHCS and pregnanediol were carried out on all patients. Vaginal smears were read according to Papanicolaou, and the endometrium and ovaries were studied histologically. The incubation experiments indicate the presence of Δ5-3β-hydroxysteroid-dehydrogenase. When androst-5-ene-3β,17β-diol was used as precursor the formation of testosterone occurred without any concomitant production of DHA and/or androstenedione. This seems to indicate the possible role of the Δ5-pathway in the formation of testosterone by post-menopausal ovarian tissue. The histochemical reactions indicated a reducing activity on NADH, lactate and glucose-6-phosphate, in certain corpora albicantia, atretic follicles and in diffuse thecoma regions in the cortical layer of the ovary. Steroid-3β-ol-dehydrogenase and β-hydroxybutyrate-dehydrogenase were found only at the edges of certain corpora albicantia, in some individual stroma cell groups and in some atretic follicles. Our studies, both biochemical and histochemical, suggest that the observed increase in the urinary oestrogens of the patients studied might in part at least, be of ovarian origin. This opinion is also supported by the postoperative oestrogen values.

scholarly journals Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

2021 ◽  
pp. 1-24
Author(s):  
Jan M. Wit ◽  
Sjoerd D. Joustra ◽  
Monique Losekoot ◽  
Hermine A. van Duyvenvoorde ◽  
Christiaan de Bruin
Keyword(s):  
Growth Hormone ◽  
Differential Diagnosis ◽  
Growth Hormone Secretion ◽  
Normal Growth ◽  
Stimulation Test ◽  
Healthy Children ◽  
Genetic Causes ◽  
Gh Secretion ◽  
Igf I

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of <i>GH1</i> or <i>GHSR</i>) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to <i>GH1</i> variants) but less on the role of <i>GHSR</i> variants. Several genetic causes of (partial) GHI are known (<i>GHR</i>, <i>STAT5B</i>, <i>STAT3</i>, <i>IGF1</i>, <i>IGFALS</i> defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.

Role of thalamic nuclei in the modulation of Fos expression within the cerebral cortex during hypertonic saline-induced muscle nociception

Neuroscience ◽  
2015 ◽  
Vol 304 ◽  
pp. 36-46 ◽  
Author(s):  
Y. Xiao ◽  
J. Lei ◽  
G. Ye ◽  
H. Xu ◽  
H.-J. You
Keyword(s):  
Cerebral Cortex ◽  
Hypertonic Saline ◽  
Thalamic Nuclei ◽  
Fos Expression

scholarly journals Phenotype and Genetic Analysis of a Syndrome Caused by an Inactivating Mutation in the Growth Hormone-Releasing Hormone Receptor: Dwarfism of Sindh1

1998 ◽  
Vol 83 (11) ◽  
pp. 4065-4074
Author(s):  
Hiralal G. Maheshwari ◽  
Bernard L. Silverman ◽  
Josée Dupuis ◽  
Gerhard Baumann
Keyword(s):  
Gh Deficiency ◽  
Postnatal Growth ◽  
N Gene ◽  
Molecular Characteristics ◽  
Clinical Genetic ◽  
Gh Treatment ◽  
Gh Secretion ◽  
Absolute Requirement ◽  
Igf I ◽  
Igf Binding

We report, in detail, a new form of familial dwarfism, including its phenotypic features, hormonal profile, and molecular basis. Following a newspaper report of severe dwarfism in two villages in the province of Sindh, Pakistan, we organized an expedition to study its clinical, genetic, and molecular characteristics. We identified 18 dwarfs (15 male, 3 female), all members of a consanguineous kindred, ranging in age from newborn to 28 yr. Mean height was 7.2 sd below the norm, with mean adult heights of 130 cm for males and 113.5 cm for females. Body proportions and habitus were normal; but head circumference was 4.1 sd, and blood pressure approximately 3 sd below the norm. There was no dysmorphism, no microphallus, and no history of hypoglycemia. Serum GH did not respond to provocative stimuli (GHRH, l-dopa, or clonidine). Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were low (5.2 ± 2.0 ng/mL and 0.42 ± 0.13 μg/mL, respectively; mean ± sd) but rose normally with GH treatment. One affected, dwarfed couple had a son, demonstrating fertility in both sexes. Clinical and endocrinological evidence suggested isolated GH deficiency with a recessive inheritance pattern. The GH-N gene was found to be intact. Linkage analysis of microsatellite chromosomal markers near other candidate genes yielded a high LOD score (6.26) for the GHRH receptor (GHRH-R) locus. DNA sequencing revealed a nonsense mutation (Glu50→Stop) in the extracellular domain of the GHRH-R. This mutation predicts a severely truncated GHRH-R; it is identical to that recently reported in four patients from two other families. Inheritance is autosomal recessive (chromosome 7p) with a high degree of penetrance. Relatives heterozygous for the mutation had moderately decreased IGF-I levels and slightly blunted GH responses to GHRH and l-dopa, but they showed only minimal or no height deficit. This syndrome represents the human homologue of the little (lit/lit) mouse and closely resembles its phenotype. It demonstrates the absolute requirement of GHRH signaling for pituitary GH secretion and postnatal growth in humans, and its relatively minor (but discernible) biological importance in extrapituitary sites. The syndrome is distinct from other forms of GH deficiency with respect to microcephaly, asymptomatic hypotension, and absence of features such as facial dysplasia, significant truncal obesity, microphallus, or hypoglycemia. Its discovery raises the possibility of milder mutations in the GHRH-R gene as potential causes for partial GH insufficiency and idiopathic short stature.

THE ROLE OF ADENOSINE A2A RECEPTORS IN THE NEUROLEPTIC-INDUCED c-Fos EXPRESSION

1998 ◽  
Vol 9 (Supplement) ◽  
pp. S93
Author(s):  
J. Wardasa ◽  
A. Pinna ◽  
A. Cozzolino ◽  
M. Morellib
Keyword(s):  
Adenosine A2a Receptors ◽  
A2a Receptors ◽  
Fos Expression ◽  
Adenosine A2a
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