Hypothalamus Paraventricular nucleus

Apelin receptor and pqrtides are co-expressed in two nuclei of the hypothalamus, the supraopticus and paraventricular nucleus which play a major role in... 

The paraventricular nucleus in the hypothalamus is located adjacent to the third ventricle and has been identified as a satiety center. Neurons in the paraventricular nucleus produce neuropeptides which inhibit feeding when injected into the brain (thyrotropinreleasing hormone (TRH), corticotropin-releasing hormone (CRH), oxytocin). 

Obviously, regulation of food intake depends on many neurotransmitters and hormones but this final section will outline the role played by central 5-HT transmission in this process. It had been the belief for some time that increased 5-HT transmission in the brain reduces food intake (Blundell 1977) and this certainly explains the satiety in rats that follows infusion of 5-HT into the paraventricular nucleus (PVN) of the hypothalamus. However, recent studies using microdialysis have found that 5-HT efflux in the lateral hypothalamus is itself increased by food intake, suggesting the existence of a feedback control system. In fact, because the increase in 5-HT efflux is greater in genetically obese rats than in their lean counterparts, it has been proposed that there is a deficiency in the 5-HT inhibition of food intake in obesity. 

FIGURE 41-1. Hypothalamic-pituitary-thyroid axis. Thyrotropinreleasing hormone (TRH) is synthesized in the neurons within the paraventricular nucleus of the hypothalamus. TRH is released into the hypothalamic-pituitary portal circulation and carried to the pituitary, where it activates the pituitary to synthesize and release thyrotropin (TSH). TSH activates the thyroid to stimulate the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3). T4 and T3 inhibit TRH and TSH secretion, closing the feedback loop. 

Figure 11.2 Increases in wakefulness after intracerebroventricular (ICV) or intrahypothalamic administration of ghrelin, neuropeptide Y (NPY), and orexin-A in the first hour of the light period in rats. LH, lateral hypothalamus MPA, medial preoptic area PVN, paraventricular nucleus asterisks denote significant differences from baseline. Orexin data are extracted from Vogel et at, J. Neuroscience Methods, 2002, 118 89-96.

The sites in brain where these drugs, and presumably 5-HT as well, act to cause such effects remain to be identified. The paraventricular nucleus (PVN) of the hypothalamus may be an important site, although some data indicate that actions on the PVN maybe sufficient but not necessary to reduce caloric intake. In addition to brain mechanisms, 5-HT may also act through peripheral mechanisms to produce satiety. 

GC, in turn, exert a very sensitive negative feedback on the HPA system at the level of the paraventricular nucleus of the hypothalamus (PVN) and the anterior pituitary, and also at the level of the hippocampus, which projects to the bed nucleus of the stria terminalis, the latter which sends off projections to the PVN. In concert with other components of the stress hormone system, the action of corticosterone displays two modes of operation (for review see De Kloet et al. 1998). In the first proactive mode, GC maintain basal activity of the HPA system and control the sensitivity or threshold of the system s response to stress. GC promote coordination of circadian events, such as the... 

Koegler-Muly SM, Owens MJ, Ervin GN, Kilts CD, Nemeroff CB (1993) Potential corticotropin-releasing factor pathways in the rat brain as determined by bilateral electrolytic lesions of the central amygdaloid nucleus and paraventricular nucleus of the hypothalamus. J Neuroendocrinol 5 95-98... 

The nonapeptide vasopressin (AVP) is synthesized in the paraventricular nucleus of the hypothalamus (PVN) and the nucleus supraopticus. Besides its role in fluid regulation, AVP is also a key modulator of the HPA system, where it potentiates the effects of CRH on adrenocorticotropic hormone (ACTH) release. Extrahypothalamic AVP-containing neurons are localized in the medial amygdala and the bed nucleus of the stria terminalis. AVP applied intracere-broventricularly or to the lateral septum has been shown to affect cognition, social behavior, and anxiety-like behavior in rodents (Insel et al. 2001). 

Oxytocin (Pitocin, Syntocinon) is a cyclic 8-amino acid peptide that is synthesized in the paraventricular nucleus of the hypothalamus and transported within hypothalamic neurons (in association with neurophysin) to the posterior pituitary for storage. Its mechanism of action involves the direct stimulation of oxytocin receptors found on the myometrial cells. Oxytocin circulates unbound in the plasma, where it has a half-Ufe of approximately 15 minutes. It is primarily inactivated in the kidneys and liver. 

Somatostatin is a 14-amino acid peptide that induces arousal and behavioral stereotypes resembling OCD [Pitman 1989). Somatostatin is synthesized in disparate regions, including the paraventricular nucleus of the hypothalamus, the cerebral cortex, striatum, and hippocampus. When administered centrally, somatostatin delays extinction of avoidant behaviors [Vecsei and Widerlov 1988). Altemus and colleagues [1993) determined CSF somato-... 

The neurotransmitter histamine (HA) exerts several functions in the hypothalamus [1-2] including an involvement in the neuroendocrine regulation of pituitary hormone secretion [3]. HA has no effect directly at the level of the pituitary gland, but influences the secretion of anterior pituitary hormones either by an exerted e.g. in the paraventricular nucleus (PVN) on other central transmitters or hypothalamic regulating factors, which subsequently regulate the release of anterior pituitary hormones. In addition, HA acts on the supraoptic nucleus (SON) in the hypothalamus where the posterior pituitary hormones are synthesized and thereby exerts a direct effect on the release of the posterior pituitary hormones. Immunohistochemical studies have revealed that the histaminergic neurons, which originate in the tuberomammillary nuclei of the posterior hypothalamus, densely innervate most of the hypothalamic areas involved in the neuroendocrine control of pituitary hormone secretion [4-5]. Within the last two decades the effect of HA on pituitary hormone secretion have been explored in several studies and it has been... 

Corticotropin-releasing factor and arginine vasopressin, which are released predominantly by the paraventricular nucleus of the hypothalamus, are important regulators of corticotropin (ACTH) release, which in turn triggers the release of cortisol and other steroids by the adrenal gland. Both the administration of certain psychoactive agents and emotional arousal originating from the limbic system are able to modify the functions of the pituitary-adrenal axis and stimulate the synthesis of cortisol. 

Kurtis Y-F L, Patel K. 2003. Alteration of NMDA NR1 receptors within the paraventricular nucleus of hypothalamus in rats with heart failure. Circ Res 93 990-997. 

Fig. 1. Location of dopaminergic perikarya (Au-A15) are depicted schematically on frontal sections (B-F) through the diencephalon of the rat. Section A is a sagittal view of the rat brain depicting the rostrocaudal location of frontal sections B-F. Abbreviations AH, anterior hypothalamus ARC, arcuate nucleus BST, bed nucleus of the stria terminalis f, fornix ic, internal capsule inf, infundibulum me, median eminence mt, mamillothalamic tract OC, optic chiasm ot, optic tract PH, posterior hypothalamus PIT, pituitary gland PeV, periventricular nucleus PVN, paraventricular nucleus RCH, retrochiasmatic area SON, supraoptic nucleus VMN, ventromedial nucleus ZI, zona incerta.

---