Stimulation of Growth Hormone Release by 5-Hydroxytryptamine (5-HT) in Cultured Rat Anterior Pituitary Cell Aggregates: Evidence for Mediation by 5-HT2B, 5-HT7, 5-HT1B, and Ketanserin-Sensitive Receptors

Papageorgiou, Anna-Pia; Denef, Carl

doi:10.1210/en.2007-0034

Cited by 29 publications

(13 citation statements)

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“…Although these reduced IGF1 concentrations are probably causing the postnatal growth retardation in Tph2 Ϫ/Ϫ mice, they could easily be secondary to undernutrition (21). Thus, further studies are required to clarify whether behavioral or sensory deficits causing malnutrition or a primary impairment of the growth hormone/ IGF1 axis by the lack of stimulatory serotonin actions (22) lead to the impaired thriving of these mice. fathers (FVB/N-F4 genetic background), only 4 survived for more than several days, compared to 8 litters of 9 born from couples of Tph2 ϩ/Ϫ mothers and Tph2 Ϫ/Ϫ fathers.…”

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confidence: 99%

Growth retardation and altered autonomic control in mice lacking brain serotonin

Alenina

Kikic

Todiras

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

312

326

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Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice (Tph2 ؊/؊ ) that lack serotonin in the central nervous system. Surprisingly, these mice can be born and survive until adulthood. However, depletion of serotonin signaling in the brain leads to growth retardation and 50% lethality in the first 4 weeks of postnatal life. Telemetric monitoring revealed more extended daytime sleep, suppressed respiration, altered body temperature control, and decreased blood pressure (BP) and heart rate (HR) during nighttime in Tph2 ؊/؊ mice. Moreover, Tph2 ؊/؊ females, despite being fertile and producing milk, exhibit impaired maternal care leading to poor survival of their pups. These data confirm that the majority of central serotonin is generated by TPH2. TPH2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life.growth retardation ͉ maternal care ͉ respiration ͉ serotonin ͉ sleep S erotonin (5-hydroxytryptamine, 5-HT) is an extracellular signaling molecule with a multitude of functions in the central nervous system (CNS) and in the periphery. 5-HT effects are conveyed by at least 13 receptors classified in 7 families, 5-HT1 to 5-HT7. Serotonin synthesis from tryptophan is initiated by the enzyme tryptophan hydroxylase (TPH) generating 5-hydroxytryptophan followed by aromatic amino acid decarboxylase (AADC), which produces 5-HT. We have recently discovered that 2 TPH isoenzymes exist in all vertebrates, TPH1 and TPH2, encoded by 2 distinct genes (1, 2). Tph1 is mainly expressed in the gut, generating serotonin that is distributed into the whole body by thrombocytes, and in the pineal gland, where the resulting 5-HT is metabolized to melatonin. The Tph1-deficient mice generated by us (2) and others (3, 4) revealed that 95% of peripheral 5-HT is produced by TPH1. They also revealed that 5-HT in platelets and other peripheral cells is involved in such diverse processes as thrombosis (5), liver regeneration (6), hepatitis (7), colon cancer (8), mammary gland plasticity (9), pulmonary hypertension (10), and bone formation (11). TPH2, on the other hand, is responsible for the synthesis of serotonin in the raphé nuclei of the brainstem, from where all central serotonergic projections originate (12). Accordingly, polymorphisms and functional mutations in the human and mouse genes for this enzyme have been linked to neurological and behavioral abnormalities (13)(14)(15)(16).In this study, we generated mice lacking TPH2 by gene targeting and analyzed the physiological consequences resulting from a lack of brain serotonin. Results and DiscussionGeneration and Basic Characteristics of Tph2-Deficient Mice. Tph2-deficient (Tph2 Ϫ/Ϫ ) mice were generated by deleting the coding sequence in exons 1 and 2 (supporting information (SI) Fig. S1 A and B). In the resulting Tph2 Ϫ/Ϫ mice, no Tph2 mRNA could be found by RT-PCR (Fig. S1C) and in situ hybridization in the brain (Fig. 1A). Immu...

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confidence: 99%

Growth retardation and altered autonomic control in mice lacking brain serotonin

Alenina

Kikic

Todiras

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

312

326

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“…Stimulatory role of 5-HT receptors on STH secretion is reported by acting through a decrease in hypothalamic somatostatin release (Ignacio Valverde et al 2000). Recent studies reported the stimulation of growth hormone release by 5-HT in cultured rat anterior pituitary cell aggregates (Papageorgiou and Denef 2007). Serotonin-mediated regulation of stress, induced activation of the hypothalamo-hypophysealadrenal system and adrenocortical regulation of brain serotonin.…”

Section: Discussionmentioning

confidence: 99%

Adrenergic, dopaminergic and serotonergic gene expression in low dose, long time insulin and somatotropin treatment to ageing rats: rejuvenation of brain function

Paulose

Sadasivam

2008

Biogerontology

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Somatotropin (GH) and insulin (INS) low dose, long-term brain rejuvenation effect was studied in the cerebral cortex using NE, EPI, DA and 5-HT receptor subtypes of young (group I-treatment started 4 weeks continued to 16 weeks) and old rats (group II-treatment started 60 weeks continued to 90 weeks). GH and INS treatment showed significant decrease in NE and EPI content in cerebral cortex of both young and old rats. alpha(2A)-adrenergic receptors showed decreased expression whereas beta(2)-adrenergic receptors showed enhanced expression with age. GH and INS treatment significantly increased alpha(2A)-adrenergic receptor protein in group I rats whereas INS treatment could increase beta(2)-adrenergic receptor protein expression in group II rats. DA and 5-HT content decrease with age. GH and INS administration showed increase in DA and 5-HT content in the brain regions-corpus striatum and brainstem of both young and old rats. Also, DA D(2) and 5-HT(2C) receptor gene expression were increased significantly by GH and INS treatment in both young and old rats. In conclusion, low dose, long-term treatment of INS and GH to ageing rats improved the adrenergic, dopaminergic and serotonergic receptor subtypes activity and rejuvenation of brain function.

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“…Since our present results, obtained after damage to the brain serotonergic system, are different from those reported after general serotonin reduction, it is suggested that peripheral serotonin may also contribute to the regulation of cytochrome P450 in the liver by affecting the enzyme in a different way. It has been found that serotonin receptors are also present in the pituitary (Abrahamson et al, 1987;Dinan, 1996;Balsa et al, 1998;Papageorgiou and Denef, 2007), adrenal gland (Lefebvre et al, 1998), thyroid gland (Csaba and Richter, 1975;Lychkova, 2013), and the liver (Ruddell et al, 2008), where they may affect the release of pituitary hormones (GH, adrenocorticotropic hormone, TSH), corticosterone, or Fig. 6.…”

Section: Tablementioning

confidence: 99%

Damage to the Brain Serotonergic System Increases the Expression of Liver Cytochrome P450

et al. 2015

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Genes coding for cytochrome P450 are regulated by endogenous hormones such as the growth hormone, corticosteroids, thyroid, and sex hormones. Secretion of these hormones is regulated by the respective hypothalamus-pituitary-secretory organ axes. Since the brain sends its serotonergic projections from the raphe nuclei to the hypothalamus, we have assumed that damage to these nuclei may affect the neuroendocrine regulation of cytochrome P450 expression in the liver. Thereby, 5,7-dihydroxytryptamine (5,7-DHT), a serotonergic neurotoxin, was injected into the dorsal and median raphe nuclei of male Wistar rats. Ten days after the neurotoxin injections, the brain concentrations of neurotransmitters, serum hormone, and cytokine levels, as well as the expression of cytochrome P450 in the liver were measured. Injection of 5,7-DHT decreased serotonin concentration in the brain followed by a significant rise in the levels of the growth hormone, corticosterone, and testosterone, and a drop in triiodothyronine concentration in the serum. No changes in interleukin (IL) levels (IL-2 and IL-6) were observed. Simultaneously, the activity and protein level of liver CYP1A, CYP3A1, and CYP2C11 rose (the activity of CYP2A/2B/2C6/2D was not significantly changed). Similarly, the mRNA levels of CYP1A1, CYP1A2, CYP2C11, and CYP3A1 were elevated. This is the first report demonstrating the effect of intracerebral administration of serotonergic neurotoxin on liver cytochrome P450. The obtained results indicate involvement of the brain serotonergic system in the neuroendocrine regulation of liver cytochrome P450 expression. The physiologic and pharmacological significance of the findings is discussed.

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Stimulation of Growth Hormone Release by 5-Hydroxytryptamine (5-HT) in Cultured Rat Anterior Pituitary Cell Aggregates: Evidence for Mediation by 5-HT2B, 5-HT7, 5-HT1B, and Ketanserin-Sensitive Receptors

Cited by 29 publications

References 102 publications

Growth retardation and altered autonomic control in mice lacking brain serotonin

Growth retardation and altered autonomic control in mice lacking brain serotonin

Adrenergic, dopaminergic and serotonergic gene expression in low dose, long time insulin and somatotropin treatment to ageing rats: rejuvenation of brain function

Damage to the Brain Serotonergic System Increases the Expression of Liver Cytochrome P450

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