Hypothalamus


Somatostatin is widely distributed throughout the brain and the gastrointestinal tract it also is found in mammalian plasma (89), in the rat retina (90), and in the human adrenal medulla (91). In the brain, the highest levels are found in the amygdala and hypothalamus, foHowed by several areas of frontal cortex (29). Significant loss of somatostatin occurs in the frontal cortex of Alzheimer s patients (92,93), and behavioral studies in rats suggest that this peptide may play a role in mediating recognition and memory (94).  [c.203]

OT receptors are localized ia the brain hypothalamus, limbic system, cortex, striatum, olfactory system, and brain stem. In the periphery, OT is best known for its stimulation of uterine smooth muscle and the milk ejection reflex. Thr , Om ]oxytocin(l—8),  [c.580]

OT receptors in the hypothalamus are regulated by steroids. OT systems in the CNS are involved in homeostasis, reproduction, and related behavior. OT is also excitatory to neurons in the CNS at nanomolar concentrations (86), but relatively Httle is known about neuronal mechanisms and pharmacology.  [c.580]

In 1973 evidence was provided for the existence of receptors which recognize opioid molecules (1). As many as eight opioid receptors are known to exist, but only four, designated as ]1 (mu), K (kappa), (sigma), and 5 (delta), are beheved to be important to the central nervous system (CNS). Several portions of the brain, including the hypothalamus and amygdala, the spinal cord, and nuclei concerned with vagal reflexes contain varying concentrations of the different types of opioid receptors.  [c.380]

The estrogenic and progestational components provide thek primary contraceptive effect by blocking ovulation, ie, preventing the selection of a dominant foUicle in the ovary by a negative feedback action on the hypothalamus and pituitary. This inhibits pituitary secretion of follicle-stimulating hormone (ESH) [9002-18-0] and luteinizing hormone (LH) [9002-67-9], with the resultant inhibition of ovulation. The estrogen component also provides stabihty to the endometrium so that unwanted breakthrough bleeding can be avoided. This combination also provides several ancillary contraceptive mechanisms by interfering with fertilization and implantation processes should ovulation occur (7).  [c.112]

Mechanisms of Endocrine Disruption. Classical toxicology deals with the effects of chemicals which act by causing damage to the function of the animal cell, and as such they have relatively little tissue specificity. Xenobiotics which disrupt the endocrine system, however, can act via a very wide variety of mechanisms. They can mimic the effect of a natural hormone (agonist), or they can block its action (antagonist). This may cause changes in the response to the hormone at its target site by affecting its ability to bind to receptors, affect its feedback action to the higher sites of endocrine control such as the hypothalamus and pituitary, or alter the hormone-dependent behaviour of the exposed animal. They can also affect the action of key enzymes of biosynthesis and metabolism that will alter circulating hormone levels, or cause structural changes which affect the function of an endocrine gland. The complexity of the issue is clearly seen in Figure 1, where disruption of any single component can cause dysfunction of a whole range of inter-related mechanisms.  [c.33]

Body temperatures are primarily sensed by temperature sensors in the hypothalamus near the center of the brain. Arterial blood flowing over and near the hypothalamus gives it information about the average thermal condition of  [c.179]

In summary, core temperature is much more important than skin temperature in determining how warm we feel. Core temperature is affected by metabolic activity and heat storage. It is relatively isolated from the environment except through whole-body heat balance and resulting heat storage. Feet and hands have little metabolic heat generation themselves and depend on warm blood from the core for their temperature. The feeling of cold feet then means that the whole body heat balance has caused the core to lose temperature and the hypothalamus is restricting heat flow to the feet in order to stabilize the core temperature.  [c.181]

Somatostatin is a tetradecapeptide of the hypothalamus that inhibits the release of pituitary growth hormone Its ammo acid sequence has been determined by a combination of Edman degradations and enzymic hydrolysis expenments On the basis of the following data deduce the pnmary structure of somatostatin  [c.1154]

Histamine in the Brain and the Histamine Neurone System. There is evidence that histamine functions as a neurotransmitter or a neuromodulator in the brain (14). In the mammalian brain, several thousand ceU bodies are located in the posterior basal hypothalamus, comprising a functional unit, the tiiberomamillary nucleus. The latter sends nerve fibers widely and unevenly to various regions from the olfactory bulb to the spinal cord. In the brain, histamine is related to functions such as the regulation of neuroendocrine and cardiovascular systems, thermoregulation, the circadian rhythm of sleep—wakehilness, behavior, vestibular function, cerebral vascular regulation, and antinociception and analgesia.  [c.136]

The secretion of anterior pituitary hormones is controUed by stimulatory and inhibitory hormones secreted from nerve ceUs found in a region of the brain called the hypothalamus. The hypothalamic neurons secrete hormones into the blood that flows directly to the anterior pituitary gland. The brain hormones (see HORMONES, BRAINOLIGOPEPTIDES) include corticotropin-releasing hormone (CRH), which stimulates the secretion of ACTH thyrotropin-releasing hormone (TRH), which stimulates the secretion of TSH gonadotropin-releasing hormone (GnRH), which stimulates FSH and LH growth hormone-releasing hormone (GRH), which stimulates GH somatostatin, which inhibits GH release and the catecholamine dopamine, which inhibits the secretion of prolactin from the anterior pituitary.  [c.171]

Corticotropin-Releasing Factor. Corticotropin-releasing factor (CRE) stimulates the release of ACTH. However, because ACTH, MSH, and P-endorphin aH arise from the same precursor, POMC, CRE regulates the release of these peptides as weH. Therefore, CRE plays a significant regulatory role in brain and hormonal function. CRE activity was first identified in the hypothalamus in the 1950s (3,4), but difficulties in the bioassay for this material precluded isolation and sequencing of this peptide until 1981 when the sequence of the 41-amino acid peptide CRE was reported (79,80). As shown in Table 1, CRE is one of the largest of the brain oligopeptides and activity appears to reside in several areas of its sequence, although much of its potency hes in the C-terminal 27 amino acids (81).  [c.203]

Neurotensin. This hormone has been isolated and characterized from acid—acetone extracts of bovine hypothalamus (118) on the basis of its hypotensive activity. Immunoreactive neurotensin is present in mammalian gut and is distributed throughout the central nervous system its highest concentration is in the hypothalamus and in the substantia gelatinosa of the spinal cord (119). Its overall brain distribution is not unlike that of enkephalin ( )  [c.204]

Gholecystokinin. Cholecystokinin (CCK) was first isolated from duodenal mucosa as a substance that produced contractions of the gallbladder (130). It is a 3-amino acid peptide that shares the same carboxy-terrninal pentapeptide sequence with gastrin. In fact, its existence in the brain was first deterrnined with gastrin antibodies (131) and this cross-reactivity has produced confusion regarding the relative localization of these two peptides in the brain. Authentic gastrin is known to be primarily localized to the magnoceUular nuclei of the hypothalamus all other gastrin-like immunoreactivity in the brain is actually CCK (132). There are relatively high quantities of CCK in the brain, eg, it has been calculated that the human brain contains 1—2 mg CCK, compared to microgram quantities of many other neuropeptides (1). One unusual aspect of CCK is the presence of a sulfated Tyr residue (see Table 1) which is added to the peptide during post-translational processing.  [c.204]

Biosynthesis. Natural estrogens are produced by steroidogenesis in various tissues. The ovary is the primary source of the hormone in nonpregnant women (69). Estradiol(3) is the most potent and primary product of the ovary, although the organ also produces estrone(2). The estrogens are ultimately formed from either androstenedione or testosterone as immediate precursors. The key reaction is the aromatization of the A-ring to yield a phenohc hydroxyl at C-3 (70). Pathological conditions, such as hirsutism and virilism, are thought to be caused by a defect of the aromatization reaction. During pregnancy the placenta produces large amounts of estrogens, especially estriol (4). Other tissues such as Hver, adipose tissue, skeleton muscle, and hypothalamus are also sources of estrogens where androgens are converted to estrone (71). In post-menopausal women, peripheral aromatization of adrenal androgens to estrone is the principal source of estrogen (72). Because significant extraglandular estrogen production occurs in adipose tissue, estrogen production is greater in obese than in thin post-menopausal women, and total estrogen production in the massively obese may be as great as, or greater than, in premenopausal women (73).  [c.242]

Pharmacological Effects. Three principal natural estrogens (E, E2, and E ) are produced by the ovary and play important roles in the development and support of female reproduction (65). The normal menstmal cycle is modulated by a variety of ovarian steroids and peptides, among which estrogen is a primary regulator. CeUs in the anterior hypothalamus secrete gonadotropin-releasing hormone (GnRH, also known as luteinizing hormone releasing hormone, LHRH) in a pulsating manner. LHRH stimulates the gonadotrope ceUs of the anterior pituitary to release both luteinizing hormone (LH) and follicle-stimulating hormone (ESH). These pituitary gonadotropic hormones induce maturation of the oocyte (an ovarian ceU which produces an ovum) and stimulate the ovarian folHcles to synthesize estrogen and progestins as well as the peptide hormone inhibin. Estrogen and progestins directiy inhibit LHRH and pituitary gonadotropin secretion and inhibit further stimulation of the ovary (83). The effect of estrogen on pituitary gonadotropin is biphasic. Early in the cycle when the concentration of estrogen is relatively low (20 60 pg/mL), estrogen inhibits LH secretion. The increasing concentration of estrogen in midcycle (200 pg/mL) leads to an increase of the frequency and ampHtude of the LH pulse. The LH surge leads to ovulation of the dominant folHcle and coincides with a transient decrease in estrogen levels. Ovulation typically occurs on day 14 of the typical 28-d cycle. The period after ovulation is the luteal phase, which is characterized by a decreasing LH pulse and a rise in progesterone concentration (83,84).  [c.242]

Menopa.use, The depletion of functional ovarian foUicles leads to the natural cessation of menses called menopause (107). After menopause, ovarian production of estradiol falls to less than 20 //g/d from a mean value of 220 //g/d during the normal menstmal cycle (108,109). This causes a deficiency of estrogen and progesterone in post-menopausal women. However, the menopause does not result in total cessation of estrogen production. Androstenedione is continuously aromatized to estrone in peripheral tissues such as fat, Hver, the skeletal muscles, hypothalamus, and hair foUicles. Because estrone is a weak estrogen, most menopausal women are hypoestrogenic.  [c.243]

Interleukin-2 [85898-30-2] (IL-2) (- IS, 000 mol wt) and its receptor occur in high levels in the hippocampus and striatum. Hippocampal IL-2 binding is increased foUowing an excitotoxic lesion. IL-2 can inhibit ACh release and the formation of long-term potentiation in the hippocampus. IL-6 ( 26, 000) is present in astrocytes, microglia, and anterior pituitary ceUs and high levels have been found in the hypothalamus. IL-1, tumor necrosis factor-a (TNE-a) and interferon-y (lEN-y) stimulate the synthesis and secretion of IL-6 which acts as a trophic factor in cultured neurons, to induce nerve growth factor (NGE) secretion in astrocytes, to stimulate the release of hormones from anterior pituitary ceUs, and to reduce feeding.  [c.539]

Regulation of Biosynthesis and Post-Translational Processing. The biosynthesis of opioid peptides. Eke that of other neuropeptides, is regulated by factors that influence messenger ribonucleic acid (mRNA) synthesis. A number of studies have examined regulation of POMC synthesis. Both cycHc adenosiae monophosphate (cAMP) and calcium have been shown to iacrease POMC expression ia pituitary cultures (29), and corticotrophin-releasiag factor [9015-71 -8] (CRF) stimulates POMC synthesis ia the pituitary (30). This effect of CRF on POMC may be mediated by the immediate early gene c-fos (31), a gene product which regulates the expression of other genes. The fact that the CRF response is mimicked by forskolin, 8-bromo-cAMP, and phorbol ester suggests that this effect is eUcited via second messenger regulation of the POMC gene (30). Glucocorticoids inhibit POMC transcription in the pituitary anterior lobe and hypothalamus, and removal of endogenous glucocorticoids by adrenalectomy increases POMC mRNA levels (32,33). These effects ate mediated by a negative glucocorticoid response element (nGRE) located on the promoter of the POMC gene (34). A region of the POMC promoter has been identified which binds several regulatory elements that act synergisticaHy to regulate POMC transcription. This region includes the nGRE binding site and an AP-1 site, which binds to immediate-early gene products (35).  [c.446]

Although many studies have focused on the analgesic effects of opioids, the endogenous opioid peptides have been found to influence a wide range of physiological functions. Opioid peptides and receptors are found in brain areas that influence respiratory and cardiovascular function. Injection of P-endorphin into the NTS results in dose-dependent and naloxone-reversible decreases in mean arterial pressure and heart rate (169). Intracistemal P-endorphin also depresses respiration in a naloxone-reversible manner (170). One aspect of opioid function that has received a great deal of interest is the effect of endogenous opioid systems on immune function (171). Both P-endorphin and Met-enkephalin enhance the cytotoxicity of natural killer cells in a manner that is inhibited by naloxone (172). In contrast, the C-terminal fragment of P-endorphin reduces the activity of natural killer cells however, this activity is not affected by naloxone (173). Endogenous opioid peptides may also influence reproductive behavior. Studies in rodents with P-endorphin (174) and an enkephalin analogue (175) have demonstrated inhibition of copulatory behavior. POMC mRNA levels are also decreased by both estrogen and testosterone (176). In contrast, estradiol has been shown to increase proenkephalin mRNA levels in the hypothalamus in a manner that coincided with the display of lordosis (177). Another hypothalamic action of opioid peptides is thermoregulation. Hyperthermia occurs after the injection of a. -agonist.  [c.450]

Although the opioid peptides have long been identified as the primary endogenous opioid ligands in brain, several groups have identified the opiate alkaloid morphine and related compounds in the tissues of several species. A nonpeptide opioid has been isolated from toad skin in sufficient quantity for purification and has the same profile as morphine in high performance Hquid chromatography (hplc), gas chromatography/mass spectrometry, radioimmunoassay, opiate receptor binding assay and bioassay (204) (see Analytical methods Chromatography Immunoassay Mass spectrometry). A nonpeptide opioid was also identified in bovine brain and adrenal gland, as well as rabbit and rat skin, that corresponded to morphine in hplc analysis. However, the concentration of the compound in these tissues was too low for further purification. Morphine and codeine have been identified in bovine hypothalamus and adrenal gland, as well as rat brain, and the presence of 6-acetylmorphine has been demonstrated in the bovine brain (205). This latter compound is a metaboUte of heroin that had not previously been identified in plants or animals. The potential biological importance of 6-acetylmorphine is that it readily enters the central nervous system, where it is then converted to morphine. Thus, it has been speculated that this compound may be a peripherally synthesized hormone that targets the central nervous system. The biological activity of endogenous opiate alkaloids has not been determined, and it is not known how they may interact with endogenous opioid peptides. Although these compounds have been shown to be synthesized in vivo their biosynthetic mechanism(s) and potential physiological significance have yet to be elucidated.  [c.451]

Human life without thyroid hormones is possible but of minimal quaUty. In the fetus, thyroid hormones affect growth and differentiation in the mature human, they regulate metaboHsm. The two principal thyroid hormones, L-thyroxine [51 8-9] (i.-thyroxine, 3,5,3, 5 -tetraiodo-L-thyronine, T (1) and T-triiodothyronine [6893-02-3] (3,5,3 -triiodo-L-thyroiiine, T ) (2) are produced by the thyroid gland and secreted into the blood stream. The minute amounts secreted are regulated by a complex system (Fig. 1) that originates in the central nervous system (CNS) and is amplified by both the hypothalamus and the anterior pituitary. These amounts can, however, be diminished by feedback loops in which circulating levels of free T and T repress production of the pituitary TSH, and perhaps of this hormone itself by inhibiting release in the hypothalamus of its Hberating hormone, TRH. In addition, amounts of hormones reaching the cells to preserve an optimal (euthyroid) condition are regulated by two plasma proteins, ie, thyroid hormone-binding globulin [9010-34-8] (TBG) and thyroid hormone-binding prealbumin [632-79-1] (TBPA). Only a small fraction (<0.3%) of the total hormones in circulation is free. Finally, tissue deiodinases convert T (possibly a prohormone) into the fivefold more active T.  [c.46]

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus.  [c.139]

Luteinizing Hormone Releasing Hormone. The isolation and synthesis of luteinizing hormone releasing hormone (LHRH) was an important advance in reproductive research (123). LHRH is a peptide hormone produced and secreted by the hypothalamus that stimulates the secretion of FSH and LH. A decapeptide with an amino acid sequence of pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, it is chemically and functionaUy similar in both males and females of aU mammalian species studied thus far. More than 1000 analogues of LHRH have been synthesized by deletion or substitution of amino acids to introduce agonist or antagonist properties. A large number of reviews have appeared discussing their therapeutic importance (124-126).  [c.123]

Logically, ADH receptor antagonists, and ADH synthesis and release inhibitors can be effective aquaretics. ADH, 8-arginine vasopressin [113-79-17, is synthesized in the hypothalamus of the brain, and is transported through the supraopticohypophyseal tract to the posterior pituitary where it is stored. Upon sensing an increase of plasma osmolaUty by brain osmoreceptors or a decrease of blood volume or blood pressure detected by the baroreceptors and volume receptors, ADH is released into the blood circulation it activates vasopressin receptors in blood vessels to raise blood pressure, and vasopressin V2 receptors of the nephrons of the kidney to retain water and electrolytes to expand the blood volume.  [c.211]

To fully understand how these pollutants can affect fish at very low levels, it is necessary to outline very briefly how the endocrine system works. It is a control system of the body which responds to internal and external signals to maintain the body in a chemical equilibrium, to regulate sexual development and the seasonal reproductive cycles, and to evoke a stress response to external threats. At its core are the hypothalamus and pituitary, which respond to neural signals from the brain and convert them into hormone messengers which act on the individual glands such as the gonads, the thyroid and the adrenal (Figure 1). The endocrine systems of all vertebrates have essentially the same components, which originated during the early evolution of fish. It is not clear how many of the differences between mammals and fish are due to evolutionary divergence and how much is attributable to the very different habitats in which they have developed. Clearly the regulation of water and mineral balance in the body fluids (osmoregulation) requires very different control in mammals to that of fish inhabiting fresh- or seawater environments, while regulation of reproduction in the predominantly egg-laying (oviparous) fish is very different from that which is required in placental mammals. In many cases it is not the hormones but the uses to which they are put which differs, although some of the steroid hormones in fish do show marked differences to those of mammals.  [c.30]

Fish possess the same essential components of the reproductive endocrine system as mammals in that external cues, such as seasonal changes in temperature or daylength, behaviour patterns of a potential mate, etc., are translated by the brain and hypothalamus into the release of gonadotrophin releasing hormone (GnRH). This in turn causes the pituitary gland, situated at the base of the brain, to release gonadotrophin which stimulates steroid synthesis in the gonads. At least some fish possess two gonadotrophins (GtH-I and GtH-II) analogous to the follicle stimulating and liiteinising hormones (FSH and LH) which regulate the female cycle in mammals. GtH-I stimulates the ovary to produce estradiol which induces production of a yolk protein (vitellogenin) by the liver, while GtH-II predominates just before spawning when it stimulates ovarian synthesis of a progestogen (17,20/i-dihydroxy-4-pregnen-3-one, usually abbreviated to 17,20/iP), which induces maturation of the oocytes prior to ovulation. This progestogen may also play a role in sperm maturation but progesterone, which is an essential hormone in the female mammal, has no known role in fish. Male fish also differ from mammals in that the major product of the testis is 11-ketotestosterone rather than testosterone. In fish, unlike mammals, the gonads of both sexes synthesise testosterone, which may play an important role in feedback to the pituitary. The gonads of fish also have some of the properties associated with the liver in mammals in that they can convert steroid hormones into metabolites. In some species of fish these metabolites may act as sexual signals (pheromones) to members of the opposite sex.  [c.31]

The close neural relationship of the hypothalamus and the pituitary gland with the brain makes them particularly vulnerable to neurotoxins such as the organophosphate pesticides and the heavy metals lead and mercury. Although the numbers of studies on these tissues are few, reflecting their very small size and inaccessibility, there is clear evidence that both these heavy metals, and the organochlorine and carbamate pesticides, can damage the neurones of the hypothalamus which are responsible for GiiRH release, leading to failure of ovaries and testes to produce yolky eggs and viable sperm. Organochlorine and organophosphate pesticides, cyanide, PAHs, PCBs, cadmium and mercury can all cause degeneration of the secretory cells of the pituitary gland and decrease its release of hormones. Industrial pollutants, such as paper mill effluents, can also affect the responsiveness of the pituitary to GiiRH released by the hypothalamus. " The feedback signal to the pituitary, which regulates plasma steroid hormone balance, can be disrupted by any xenobiotic that has hormone mimicking properties. Organochlorine pesticides, such as the lindane impurity /i-HCH, mimic natural estrogen and induce a negative feedback response in the pituitary. This could account for many of the reports of reproductive failure of fish in waters such as the Great Lakes that are heavily polluted with organochlorines.  [c.34]

The hormones of the thyroid, in concert with those of the adrenal gland and growth hormone from the pituitary, regulate energy utilisation, metabolic rate and growth. Since thyroid hormones are incorporated into the developing egg from maternal sources, they may also be involved in larval development, although their role in this is still far from clear. The main thyroid hormones, thyroxine (TJ and triiodothyronine (Tj), are tetra- and triiodinated derivatives of 4-hydroxydiphenyl ether and as such have close structural similarities to other planar halogenated aromatic compounds such as PCBs, dioxins and DDT. It is therefore not surprising that such chemicals are those most suspected of inducing thyroid dysfunction by competing for receptors. As in mammals, thyroid function can be disrupted by action of pollutants at several sites, including production of thyrotrophin releasing hormone (TRH) from the hypothalamus, release of thyroid stimulating hormone (TSH) from the pituitary, synthesis of T4 by the thyroid or its conversion in the thyroid and liver into Tj (Figure 1). The study of thyroid activity has undoubtedly been inhibited by the difficulty of isolating the tissue which, unlike mammals, does not form a distinct gland but is scattered as isolated cells around the ventral aorta.  [c.42]

Many environmental factors (e.g. daylight length) also affect the breeding cycle of birds. However, these tend to be mediated through the hypothalamus-pituitary axis, resulting in gonadotrophin release of FSH and leiitenising hormone (LH), which in turn control testosterone and oestrogen production in males and females.  [c.67]


See pages that mention the term Hypothalamus : [c.504]    [c.190]    [c.202]    [c.202]    [c.203]    [c.203]    [c.539]    [c.568]    [c.574]    [c.578]    [c.578]    [c.445]    [c.446]    [c.446]    [c.386]    [c.218]    [c.31]    [c.91]    [c.180]    [c.180]   
12 Endocrine Disrupting Chemicals (1999) -- [ c.30 , c.33 , c.34 ]

Industrial ventilation design guidebook (2001) -- [ c.1450 ]