The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism

Luiten, P.G.M.; Horst, ter Gert; Steffens, A.B.

doi:10.1016/0301-0082(87)90004-9

Cited by 371 publications

(142 citation statements)

References 107 publications

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“…While these structures are important in regulating the negative feedback effects of CORT on HPA axis activity (8,44,45), there is little evidence that they have a primary or direct function in the control of feeding behavior (184). This is consistent with the evidence that CORT or ALDO administration to these areas has little impact on nutrient intake (183).…”

Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 82%

“…In addition to its major function in controlling pituitary ACTH release and adrenal secretion of CORT and ALDO across the circadian rhythm (25,(184)(185)(186), the PVN, through its neutral connections with the brainstem, is believed to be active in integrating information from multiple areas involved in food intake and metabolism (22,25,174,184,187). This nucleus, therefore, is particularly well positioned to link the actions of the circulating steroids to central mechanisms involved in nutrient balance.…”

Section: Differential Role Of Steroid Receptor Subtypes In Nutrient Imentioning

confidence: 99%

“…Within the hypothalamus, the arcuate nucleus (ARC), while being unresponsive to the feeding effects of steroid implants (183), may be particularly important in mediating CORT's interaction with neuropeptide systems that govern circadian rhythms of food intake and particularly carbohydrate ingestion (see below). Additional areas involved in modulating ingestion and metabolism include the ventromedial (VMH ) and lateral (LH) hypothalamic regions (24,137,143,184). These sites are active in controlling circulating levels of insulin and glucose and, glucose, or stimulate respiratory quotient indicating an enhancement in carbohydrate utilization (28,203,204).…”

Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 99%

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Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

194

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 82%

Section: Differential Role Of Steroid Receptor Subtypes In Nutrient Imentioning

confidence: 99%

Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 99%

See 1 more Smart Citation

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

194

127

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“…Based on different projections, possible functions, and histochemical properties, the VMN can be organized into dorsomedial, central, and ventrolateral regions (Altman and Bayer, 1986;Canteras et al, 1994;Canteras, 2002). VMN neurons send projections to adjacent hypothalamic regions and to other brain regions, including the bed nucleus of stria terminalis and the amygdala of limbic system (Altman and Bayer, 1986;Luiten et al, 1987;Swanson, 1987;Canteras et al, 1994). Although the precise molecular and chemical nature of the VMN circuitry remains to be defined, recent studies have proposed that the orphan nuclear receptor steroidogenic factor 1 (SF-1) is required for proper VMN development and function (Ikeda et al, 1995;Shinoda et al, 1995;Majdic et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons

Tran

Lee

Marı́n

et al. 2003

Molecular and Cellular Neuroscience

101

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The ventromedial hypothalamic nucleus (VMN) is known to mediate autonomic responses in feeding and reproductive behaviors. To date, the most definitive molecular marker for the VMN is the orphan nuclear receptor steroidogenic factor-1 (SF-1). However, it is unclear whether SF-1 functions in the VMN as it does in peripheral endocrine organ development where loss of SF-1 results in organ agenesis due to apoptosis. Here, we provide evidence that SF-1 has a distinct role in later stages of VMN development by demonstrating the persistence of VMN precursors, the misexpression of an early marker (NKX2-1) concomitant with the absence of a late marker (BDNF neurotrophin), and the complete loss of projections to the bed nucleus of stria terminalis and the amygdala in sf-1 null mice. Our findings demonstrate that SF-1 is required for terminal differentiation of the VMN and suggest that transcriptional targets of SF-1 mediate normal circuitry between the hypothalamus and limbic structures in the telencephalon.

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“…Many centrally-acting agents have effects on core temperature, but this was not observed with RS-45041-190 in conscious rats. An effect of RS-45041-190 on arousal might be expected because of the high density of binding sites for this agent in the locus coeruleus (MacKinnon et al, 1995c), a nucleus which has long been associated with vigilance, arousal and sleep-wakefulness (see Carlson, 1991 Luiten et al 1987), and to the nucleus tractus solitarius, which contains neurones involved in relaying gustatory information (Doetsch & Erickson, 1970 (Blundell & Latham, 1982;Leibowitz, 1992;Rowland, 1993) are required with this agent before the role of its receptors in feeding behaviour can be established.…”

Section: Discussionmentioning

confidence: 99%

RS‐45041‐190: a selective, high‐affinity ligand for I₂ imidazoline receptors

Brown¹,

MacKinnon²,

Redfern³

et al. 1995

British J Pharmacology

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1 RS-45041-190 (4-chloro-2-(imidazolin-2-yl)isoindoline) showed high affinity for 12 imidazoline receptors labelled by [3H]-idazoxan in rat (pKi = 8.66 ± 0.09), rabbit (pKi = 9.37 ± 0.07), dog (pKi = 9.32 ± 0.18) and baboon kidney (pKi = 8.85 ± 0.12), but had very low affinity for a2-adrenoceptors in rat cerebral cortex (pKi = 5.7 ± 0.09).2 RS-45041-190 showed low affinity for other adrenoceptors, dopamine, 5-hydroxytryptamine, and muscarinic receptors and dihydropyridine binding sites (selectivity ratio>1000). 3 RS-45041-190 showed moderate potency for the inhibition of monoamine oxidase A in vitro (pIC50= 6.12), but had much lower potency for monoamine oxidase B (pICs = 4.47), neither of which equated with its affinity for I2 receptors. 4 RS-45041-190 (0.001 to 3 mg kg-', i.v. and 1 ng-50 yg i.c.v.) had only small, transient effects on blood pressure and heart rate in anaesthetized rats. In conscious rats, RS-45041-190 had no effect on body core temperature or tail skin temperature (1 mg kg-', s.c.) or on activity or rotarod performance (10 mg kg-1, i.p.). There were also no effects on barbiturate sleeping time in mice after doses of 1-10 mg kg-, i.p.5 RS-45041-190 (10 and 25 mg kg-', i.p.) significantly increased food consumption in rats for up to 4 h after dosing, but unlike idazoxan (10 mg kg-, i.p.) did not increase water consumption. 6 RS-45041-190 is therefore a selective, high-affinity ligand at I2 imidazoline receptors and its hyperphagic effect may suggest a role for I2 imidazoline receptors in the modulation of appetite. However, in the absence of a selective agonist it is unclear whether this ligand is an agonist or an antagonist at I2 receptors.

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The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism

Cited by 371 publications

References 107 publications

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons

RS‐45041‐190: a selective, high‐affinity ligand for I₂ imidazoline receptors

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The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism

Cited by 371 publications

References 107 publications

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons

RS‐45041‐190: a selective, high‐affinity ligand for I2 imidazoline receptors

Contact Info

Product

Resources

About

RS‐45041‐190: a selective, high‐affinity ligand for I₂ imidazoline receptors