Preoptic Anterior Hypothalamus Research Articles

Role of the central amygdala in social communication in Syrian hamsters ( Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) controls a form of scent marking called flank marking. Microinjection and lesion studies have identified several components of the neural circuit controlling this behavior. Microinjection of AVP into the medial preoptic–anterior hypothalamus (MPOA-AH), lateral septal nucleus (LS), bed nucleus of stria terminalis (BNST), and periaqueductal gray (PAG) stimulates an intense bout of flank marking. Lesions of areas such as the MPOA-AH and the LS inhibit flank marking. Other studies employing Fos immunocytochemistry suggest that the central amygdala (Ce) might be a component of this neural circuit. The purpose of the present study was to assess the significance of the Ce in regulation of AVP-induced flank marking. In Expt. 1A, the Ce of hamsters were either lesioned with ibotenic acid or sham-lesioned. In Expt. 1B, the Ce of hamsters were either lesioned electrolytically or sham-lesioned. All lesions were made bilaterally. One week later, hamsters were microinjected with AVP into the MPOA-AH and immediately tested for flank marking. In Expt. 2, the hamsters were microinjected with AVP into the Ce and were immediately tested for flank marking. Ibotenic lesions of the Ce reduced flank marking and electrolytic lesions completely inhibited flank marking in response to AVP microinjected into the MPOA-AH. Sham-lesions or lesions placed in other areas of the amygdala resulted in intense bouts of AVP-induced flank marking and flank grooming. No flank marking or flank grooming was observed in response to AVP microinjected into the Ce. These data indicate that the Ce plays a critical role in AVP-induced flank marking, although flank marking is not induced by AVP within the Ce itself.

Interaction between norepinephrine and prostaglandin E2 in the preoptic area of guinea pigs.

The release of norepinephrine (NE) and prostaglandin E2 (PGE2) in the preoptic-anterior hypothalamus (POA) by systemically administered pyrogens suggests that both substances may mediate the febrile response. To investigate their possible interaction, we measured directly the levels of PGE2 in the extracellular fluid of the POA of conscious guinea pigs microdialyzed intrapreoptically with exogenous NE over the entire course of their febrile response to endotoxin. Acidified and buffered NE (NEa, NEb), artificial cerebrospinal fluid (aCSFa, aCSFb), and vehicle (Veha, Vehb) were tested. All but aCSFb depressed the febrile response to endotoxin. The microdialysis of aCSFa, aCSFb, Veha, Vehb, and NEa did not change basal preoptic PGE2 levels. However, NEb, at a dose that by itself did not affect body temperature (Tb), caused a large elevation in preoptic PGE2. The intravenous injection of endotoxin increased the level of PGE2 in the POA. NEb potentiated this increase, whereas NEa, aCSFa, and Vehb reduced it; Veha reduced it for the first 60 min and enhanced it for the last 90 min of the experiment. Thus these data suggest that the low pH of the NE solute and/or its Veh may confound the observed effects of NE on the Tb and preoptic PGE2 induced by endotoxin. We surmise that this is due to a neurotoxic action of the antioxidants and the acidity of the solution on thermosensitive neurons in the POA. Hence, the results of experiments using exogenous, usually acidified, NE preparations that often also contain additives should be interpreted with caution.

Glutamate and vasopressin interact to control scent marking in Syrian hamsters (Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH) controls a form of scent marking called flank marking. Another neurochemical signal that may interact with AVP to control flank marking is glutamate. We tested the hypothesis that glutamate interacts with AVP in the MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA-AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA antagonist, or GAMS, a non-NMDA antagonist or propranolol, a β norepinephrine antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high levels of marking in response to AVP alone or to a combination of AVP and propranolol. In contrast, the frequency of marking was significantly reduced in response to a combination of either AVP and AP-5 or AVP and GAMS. These data support the hypothesis that stimulation of flank marking by AVP within the MPOA-AH requires the activity of glutamate.

Glutamate and vasopressin interact to control scent marking in Syrian hamsters ( Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH) controls a form of scent marking called flank marking. Another neurochemical signal that may interact with AVP to control flank marking is glutamate. We tested the hypothesis that glutamate interacts with AVP in the MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA-AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA antagonist, or GAMS, a non-NMDA antagonist or propranolol, a β norepinephrine antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high levels of marking in response to AVP alone or to a combination of AVP and propranolol. In contrast, the frequency of marking was significantly reduced in response to a combination of either AVP and AP-5 or AVP and GAMS. These data support the hypothesis that stimulation of flank marking by AVP within the MPOA-AH requires the activity of glutamate.

Disruption of neuroendocrine function in atlantic croaker exposed to Aroclor 1254

To investigate the effects of a polychlorinated biphenyl (PCB) mixture (Aroclor 1254) on reproductive neuroendocrine function, male Atlantic croaker ( Micropogonias undulatus) were exposed to the PCB mixture in the diet (0.1 mg/100. g body wt/day) for 30 days during gonadal recrudescence. Concentrations of the monoamines (5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE)) and their major metabolites (5-hydroxyindolacetic acid, dihydroxyphenylacetic acid and 3-methoxytyramine) were measured in the preoptic-anterior hypothalamus (POAH) and medial and posterior hypothalamus (MPH) using HPLC with electrochemical detection. There was a significant decline in 5-HT and DA concentrations and an increase in their metabolite to parent amine ratios in both the POAH and MPH of Aroclor 1254-exposed fish. In addition, Aroclor 1254 exposure resulted in the loss of the in vitro gonadotropin (GtH) response to stimulation by a luteinizing hormone-releasing hormone analog (LHRHa). The reduced availability of 5-HT in the nerve terminals may be responsible for the loss of pituitary GtH response to stimulation by LHRHa. These results support the hypothesis that Aroclor 1254-induced alterations in pituitary gonadotropin release may be mediated, at least partially, by altered hypothalamic serotonergic activity.

Neural circuitry controlling vasopressin-stimulated scent marking in Syrian hamsters (Mesocricetus auratus)

In Syrian hamsters, arginine vasopressin (AVP) plays a critical role in the control of a form of scent marking called flank marking. Microinjection of AVP into the medial preoptic-anterior hypothalamus (MPOA-AH), lateral septal nucleus (LS), bed nucleus of the stria terminalis (BNST), and the periaqueductal gray (PAG) stimulates high levels of flank marking. Microinjection of an antagonist of the V1a-AVP receptor into sites such as the MPOA-AH inhibits expression of flank marking. The purpose of the present study was to investigate the neural circuit controlling flank marking by localizing the induction of Fos protein in response to the microinjection of AVP, a V1a-AVP antagonist (AVPA) or saline into the MPOA-AH. Immediately after microinjection, hamsters were placed in a clean cage and their behavior was videotaped for 10 minutes. Ninety minutes after the behavioral experiment hamsters were perfused and their brains removed for subsequent immunocytochemical localization of Fos protein. The number of Fos-positive neurons was significantly greater in the BNST, PAG, and central amygdala (Ce) following the microinjection of AVP than following the microinjection of either AVPA or saline. In AVP-injected animals, the number of Fos-labeled cells in the Ce, PVN, and PAG increased with increased frequency of either flank marking or flank gland grooming. These data support the hypothesis that neurons within the MPOA-AH, BNST, and PAG play an important role in the control of flank marking and suggest that the Ce may be a previously unrecognized part of this neural circuit.

Respiratory responses to preoptic/anterior hypothalamic warming during sleep in kittens.

The preoptic/anterior hypothalamic (POAH) area of 12-48-day-old unanaesthetized, unrestrained kittens was warmed with a diathermic probe to assess respiratory responses to a central thermal challenge during sleep. During quiet sleep (QS), warming of the POAH by 1.4-3.8 degrees C induced periods of tachypnoea (panting) interspersed with periods of slower respiration; the percentage of time spent in panting increased as the kittens matured. During rapid eye movement (REM) sleep, POAH warming induced a much smaller increase in respiratory rate and no sustained panting. Analysis of the dynamics of panting (in QS only, since panting did not occur in REM) revealed several changes from breathing patterns of normal respiration. During panting, the increased respiratory rate did not result from equal changes in inspiratory and expiratory times; inspiratory times accounted for a larger portion of the decline in total respiratory cycle time. Amplitude of diaphragmatic electromyographic activity showed an age-dependent response to thermal panting, which resulted in age-dependent changes in ventilation and inspiratory drive. The interspersion of slower with faster respiratory rates suggests a competition of thermoregulatory and respiratory homeostatic mechanisms. The age-dependent ventilatory responses to thermal panting suggest greater vulnerability to thermal stress at particular ages, and may have implications for the sudden infant death syndrome.

Ovarian hormones alter the behavioral response of the medial preoptic anterior hypothalamus to arginine-vasopressin.

In Syrian hamsters (Mesocricetus auratus) arginine-vasopressin (AVP) within the medial preoptic-anterior hypothalamus (MPOA-AH) plays a critical role in the control of a hormone-dependent behavior called flank marking. The present study investigated whether ovarian hormones influence flank marking by altering the response of the MPOA-AH to AVP. The amount of flank marking stimulated by microinjection of AVP (9 microM in 200 nl saline) into the MPOA-AH varied significantly over the 4 days of the estrous cycle with the lowest levels of flank marking observed on estrus. A second experiment demonstrated that administration of progesterone significantly reduced AVP-stimulated flank marking in estradiol-treated ovariectomized hamsters. These data support the hypothesis that the changing levels of estradiol and progesterone during the estrous cycle influence flank marking by altering the sensitivity or response of the MPOA-AH to AVP.

Sleep deprivation in rats with preoptic/anterior hypothalamic lesions

Chronic total sleep deprivation (TSD) of rats by the disk-over-water method reliably produces initial increases and subsequent decreases in waking intraperitoneal ( T ip ) and hypothalamic ( T hy ) temperatures, progressive increases in energy expenditure, skin lesions on the tail and plantar surfaces, debilitated appearance, and eventual death. We investigated the possible role of the preoptic/anterior hypothalamus (POAH) in the mediation of the TSD effects by comparing these effects in POAH-lesioned and unlesioned rats. Bilateral POAH lesions sufficient in size to impair homeothermic responses to changes in ambient temperature did not produce TSD-like temperature changes under baseline ambient temperatures of 28–29°C, implying that the thermoregulatory changes produced by TSD do not result from impairment of the lesioned area. However, the possibility remains that the TSD effects are mediated by damage to POAH areas that were not lesioned. During TSD, lesioned and unlesioned rats showed similar progressive increases in energy expenditure, but the lesioned rats showed earlier, steeper, and eventually greater declines in T ip and T hy . This result suggests that in unlesioned rats the POAH may counter-regulate against, and thereby attenuate, the reduction in heat retention caused by TSD. This failure of regulation in lesioned rats is consistent with their impaired response to ambient temperature change and implies that, in unlesioned rats, some POAH thermoregulatory mechanisms continue to function normally during TSD. Lesioned rats did not show the characteristic TSD-induced early increases in T ip and T hy . This result could imply either that heat retention was so compromised that body temperatures did not rise in spite of a TSD-induced increases in thermoregulatory setpoint, or that the setpoint increase in unlesioned rats is POAH-mediated. Notwithstanding the greater T ip and T hy declines in lesioned rats, they survived the TSD procedure longer than the unlesioned rats, thus supporting previous indications that death did not result from hypothermia.

The effects of N-methyl- d-aspartate (NMDA) and non-NMDA receptor agonist and antagonists on hypothalamic neurones in the anaesthetized rat which respond to changes in scrotal skin temperature

There are neurons in the pre-optic anterior hypothalamus of the anaesthetised rat which respond to changes in scrotal skin temperature. Neuronal firing rate can be increased by raising the scrotal skin temperature above 36°C, and also by ionophoretic application of either N-methyl- d-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) (a non-NMDA receptor agonist). The increase in neuronal firing evoked by thermal stimulation was prevented or diminished by concurrent application of either d-2-amino-5-phosphonopentanoic acid (D-AP5) (an NMDA receptor antagonist) or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F)quinoxaline (a non-NMDA receptor antagonist) at doses which were sufficient to abolish or significantly diminish the effect of the specific agonist. It is probable that both NMDA and non-NMDA receptors are involved in the scrotal thermoafferent pathway in the rat.

Preoptic/anterior hypothalamic neurons: thermosensitivity in rapid eye movement sleep

The thermosensitivity of 15 warm-sensitive neurons (WSNs) and 19 cold-sensitive neurons (CSNs) from the medial preoptic/anterior hypothalamus (POAH) was tested during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by local POAH warming and cooling in freely moving cats. Thermosensitivity was quantified by three criteria, Q10, impulses per second per degree Celsius, and percent change per degree Celsius. Irrespective of the criterion used, WSNs did not exhibit a significant change in thermosensitivity during REM sleep compared with wakefulness and NREM sleep. In contrast, CSNs exhibited decreased mean thermosensitivity during REM sleep compared with wakefulness. CSNs as a group did not retain significant thermosensitivity in REM sleep. These findings are consistent with evidence that thermoeffector responses to cooling are lost in REM sleep, whereas some responses to warming are preserved.

Identification of hypothalamic nuclei involved in osmoregulation using fos immunocytochemistry in the domestic hen (Gallus domesticus), Ring dove (Streptopelia risoria), Japanese quail (Coturnix japonica) and Zebra finch (Taenopygia guttata)

Domestic hens were injected intraperitoneally with hypertonic or isotonic saline and killed 0.5, 1, 2, 6, 12 and 24 h later. Japanese quail, Ring doves and Zebra finches were treated in the same way and killed 2 h later. Using fos immunocytochemistry, fos-positive cells were visualized in the preoptic-anterior hypothalamus. In all species, two hours after treatment with hypertonic but not with isotonic saline, a prominent cluster of fos-positive cells was seen close to the mid-line, dorsal to the anterior part of the third ventricle, in and around the nucleus commissurae pallii. The cell cluster was associated with the dorsal region of the organum vasculosum laminae terminalis and passed caudo-dorsally above the anterior commissure into the area of the subfornical organ, spreading diffusely into the nucleus septalis medialis and the nucleus dorsomedialis anterior thalami. The maximal expression of c-fos was seen 2 h after treatment with hypertonic saline: weak fos immunoreactive product was seen at 0.5, 1 h and 6 h but not after 12 and 24 h. In all birds, 2 h after treatment with hypertonic but not with isotonic saline, fos-positive cells were also seen in the nucleus paraventricularis and nucleus supraopticus. Double immunocytochemistry in the domestic hen with an antibody to vasotocin showed that these fos-positive cells were classical magnocellular vasotocinergic neurones. This study extends earlier studies in birds using lesioning and electrophysiological techniques to identify the precise cellular localization of the avian “osmoreceptive complex” projected onto a stereotaxic atlas.

Local preoptic/anterior hypothalamic warming alters spontaneous and evoked neuronal activity in the magno-cellular basal forebrain

Local warming of the medial preoptic/anterior hypothalamus (POAH) promotes sleep, enhances EEG slow-wave activity during sleep, and suppresses arousal-related discharge in neurons of the midbrain reticular formation (MRF) and the posterior lateral hypothalamic area (PLHa). Another important site of sleep and arousal regulation, and a potential site of POAH thermal modulation, is the magnocellular basal forebrain (BF). We examined the ability of local POAH warming during wakefulness to influence the spontaneous and evoked discharge of neurons recorded in the BF of unanesthetized, unrestrained cats. Seventy of 174 BF neurons responded to 60–90 s periods of POAH warming with either increases or decreases in discharge rate. Forty-one of the 70 responsive cells displayed suppression of waking discharge during warming. Discharge rate in these cells declined by an average of 26.04 ± 2.76%/°C of POAH temperature increase. The majority of warming-suppressed BF cells (73%) displayed higher rates of discharge during periods of wakefulness compared to periods of sleep. Twenty-nine of 70 responsive cells responded to POAH warming with an average increase in discharge rate of 43.81 ± 6.26%/°C. A majority of these neurons (62%) exhibited higher spontaneous discharge rates during sleep compared to waking. Orthodromic excitatory responses were evoked in 29 BF cells by electrical stimulation of the MRF or PLHa. Thirteen of 29 cells displayed a waking-related discharge pattern, and responded to POAH warming with a significant suppression of evoked excitation. For a group of 15 behavioral state-indifferent cells (i.e., cells displaying no modulation of spontaneous discharge rate across the sleep-waking cycle), POAH warming had no effect on evoked excitatory responses. These results support the hypothesis that thermosensitive neurons of the POAH exert control of sleep-waking state, in part, via modulation of arousal- and sleep-regulating cell types within the magnocellular BF.

Effect of adrenal medullectomy on responses in heat production, plasma catecholamines and body temperature of burned rats to changes in the temperature of the hypothalamus

Burn (B) and control (C) rats with and without adrenal medullectomy (Adx) 9–11 days postburn underwent warming and cooling of the preoptic anterior hypothalamus (POAH) during calorimetry at 22° and 28° C ambient. Blood was drawn for catecholamine assay during each displacement of the POAH temperature ( T hy). The heat production ( H p) for the AdxB group at 22° and 28° C was not different from the H p for the sham AdxB group (80 ± 4 vs 86 ± 8 at 22° C, 58 ± 8 vs 64 ± 7 W/m 2 at 28° C) in spite of there being no detectable circulating epinephrine (E) for the AdxB groups. Cooling of the POAH of the AdxB 22° C group, however, did not induce a further increment in H p, in contract to all other groups. T hy demonstrated good significant negative linear correlation with H p for all groups. The resulting slopes were not significantly different from one another, indicating no difference in thermal sensitivity of the POAH between the groups. In four of eight groups plasma norepinephrine (NE) demonstrated positive correlation with H p and in five of eight groups negative correlation with T hy. Plasma E values did not correlate with H p and demonstrated negative correlation with T hy in two of four possible groups. These data show that postburn hypermetabolism is not dependent on E in the rat and suggest that NE may be calorigenic in burned rats.

Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters

Oxytocin (OXT) has been implicated in the control of a variety of social and reproductive behaviors in several species. The purpose of the present study was to test the hypothesis that OXT activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays a critical role in the expression of sexual receptivity in Syrian hamsters. The first 2 experiments investigated whether OXT would stimulate sexual receptivity in female hamsters in a dose-dependent manner. A 3rd experiment investigated whether sexual receptivity would be inhibited when endogenous OXT activity was blocked. Microinjection of OXT into the MPOA-AH or the VMH induced sexual receptivity in a dose-dependent manner in ovariectomized (OVX) hamsters primed with estradiol. Microinjection of a selective OXT antagonist, d(CH 2) 5[Tyr(Me) 2Thr 4,Tyr-NH 29] ornithine vasotocin into the MPOA-AH or the VMH significantly reduced the levels of sexual receptivity exhibited by OVX hamsters administered estradiol and progesterone. These findings support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.

Regulation of posterior lateral hypothalamic arousal related neuronal discharge by preoptic anterior hypothalamic warming

The posterior lateral hypothalamus (PLH) is a brain region involved in cortical activation and maintenance of behavioral arousal. Spontaneous and evoked neuronal activities were recorded in the PLH of cats before and during local warming of the preoptic-anterior hypothalamus (POAH). Forty-six percent of PLH neurons recorded in awake cats decreased spontaneous discharge during POAH warming. In the absence of POAH warming, these same cells exhibited significantly lower discharge rates in non-rapid eye movement (NREM) sleep compared to waking. Responses of PLH neurons to POAH warming were also investigated in sleeping cats to determine whether hypothalamic thermosensitive neurons modulated sleep-wake regulation across arousal states. POAH warming had no influence on spontaneous activities of PLH neurons during NREM sleep, but suppressed activity of a small subset of neurons during rapid eye movement (REM) sleep. Thus, during wakefulness or REM sleep, hypothalamic thermosensitive neurons may modulate behavioral state via inhibition or disfacilitation of arousal systems.

Thermoregulatory responses to thermal stimulation of the preoptic anterior hypothalamus in the red fox ( Vulpes vulpes)

The preoptic anterior hypothalamus (POAH) thermoregulatory controller can be characterized by two types of control, an adjustable setpoint temperature and changing POAH thermal sensitivity. Setpoint temperatures for shivering ( T shiver) and panting ( T pant) both increased with decreasing ambient temperature ( T a), and decreased with increasing T a. The POAH controller is twice as sensitive to heating as to cooling. Metabolic rate (MR) increased during both heating and cooling of the POAH. Resting temperature of the POAH was lower than internal body temperature ( T b) at all temperatures. This indicates the presence of some form of brain cooling mechanism. Decreased T b during POAH heating was a result of increased heat dissipation, while higher T b during POAH cooling was a result of increased heat production and reduced heat dissipation. The surface temperature responses indicated that foxes can actively control heat flow from body surface. Such control can be achieved by increased peripheral blood flow and vasodilation during POAH heating, and reduced peripheral blood flow and vasoconstriction during POAH cooling. The observed surface temperature changes indicated that the thermoregulatory vasomotor responses can occur within l min following POAH heating or cooling. Such a degree of regulation can be achieved only by central neural control. Only surface regions covered with relatively short fur are used for heat dissipation. These thermoregulatory effective surface areas account for approximately 33% of the total body surface area, and include the area of the face, dorsal head, nose, pinna, lower legs, and paws.

What roles does the organum vasculosum laminae terminalis play in fever in rabbits?

Experiments were designed to clarify the role of the brain's organum vasculosum laminae terminalis (OVLT) in the development of fever in rabbits. Rectal and ear skin temperatures were recorded in conscious animals in which the OVLT had been electrolytically destroyed or in which the preoptic anterior hypothalamus (PO/AH) had been transected bilaterally. When the OVLT had been ablated the febrile responses to intravenous injection of interleukin-1 beta (IL-1 beta) or tumour necrosis factor alpha were significantly attenuated, while those to intracerebroventricular injection of IL-1 beta were not affected. Fever induced by intracerebroventricular injection of prostaglandin E2 (PGE2) was prolonged significantly. The febrile responses to intravenous injection of IL-1 beta and to intracerebroventricular injection of PGE2 were attenuated when the transection was located caudally to the anterior wall of the third ventricle and extended laterally more than about 3 mm in the ventricular wall. The results show that the OVLT region is a site through which signals to increase body temperature are transferred from the blood to the brain in rabbits.

Novel presence of luteinizing hormone/human chorionic gonadotropin (hCG) receptors and the down-regulating action of hCG on gonadotropin-releasing hormone gene expression in immortalized hypothalamic GT1-7 neurons.

We recently demonstrated that rat preoptic area and anterior hypothalamus, sites of GnRH neurons, contain receptors for LH/hCG. We investigated in the present study whether LH/hCG receptor and GnRH genes are coexpressed in the same neurons and whether LH/hCG can directly regulate GnRH gene expression in immortalized hypothalamic GT1-7 neurons. The immunostaining for both LH/hCG receptors and GnRH are present in the same neurons in rat preoptic area and the GT1-7 neurons. The reverse transcription-nested polymerase chain reaction generated an expected 255-basepair LH/hCG receptor fragment in GT1-7 neurons. Northern blotting showed the presence of a major 1.8-kilobase and minor 2.6- and 4.3-kilobase receptor transcripts. Immunoblotting detected an 80-kilodalton receptor protein. Covalent receptor cross-linking studies showed that [125I]hCG binds to an 80-kilodalton protein with a specificity expected of LH/hCG receptors. Scatchard plot analysis demonstrated that GT1-7 neurons contain a single class of high affinity (Kd = 3.8 x 10(-11) M) and low capacity (5000 sites/neuron) LH/hCG receptors. Culturing GT1-7 neurons with highly purified hCG resulted in a dose- and time-dependent decrease in steady state GnRH, but not glyceraldehyde-3-phosphate dehydrogenase, messenger RNA (mRNA) levels. Human and rat LH, but not hCG alpha or -beta, FSH, or TSH, mimicked the down-regulating action of hCG on GnRH mRNA levels. Pretreatment of GT1-7 neurons with LH/hCG receptor antisense, but not sense, phosphorothioate oligodeoxynucleotides for 48 h resulted in decreases in [125I]hCG binding and the GnRH mRNA response to exogenous hCG. The half-life of GnRH mRNA transcripts, as determined by blocking transcription by actinomycin-D, was 32.5 +/- 2.5 h. This half-life was virtually unchanged by treatment with 100 ng/ml hCG (30.5 +/- 3.5 h). Treatment of GT1-7 neurons with 100 ng/ml hCG resulted in a dramatic decrease in nuclear run-on transcription of GnRH, but not beta-actin, gene compared to that in the controls. The same hCG concentrations and time points that decreased steady state GnRH mRNA levels also decreased cellular GnRH protein levels. Paradoxically, hCG stimulated the secretion of preexisting GnRH until the levels were depleted. In summary, GnRH neurons in the rat preoptic area and GT1-7 neurons coexpress LH/hCG receptor gene. Treatment of GT1-7 neurons with LH/hCG results in a decrease in steady state GnRH mRNA levels. This decrease is dose and time dependent and hormone specific, and requires the presence of cellular LH/hCG receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

The response in heat production, plasma catecholamines, and body temperature of burned rats to hypothalamic temperature displacement.

Rats, with the preoptic anterior hypothalamus implanted with two thermodes and a thermocouple reentry tube, had simultaneous direct and indirect calorimetry performed [during the ninth to eleventh postburn day interval] at ambient temperatures of 22 degrees and 28 degrees C. During calorimetry, blood was drawn at baseline and near the end of each period of displacement of the preoptic anterior hypothalamus temperature for catecholamine assay. Cooling the preoptic anterior hypothalamus resulted in a significant increase in heat production and plasma epinephrine and norepinephrine concentrations for both burn and control groups at 22 degrees C and 28 degrees C (p < 0.05 for all comparisons). Heat production demonstrated consistent negative linear correlation with preoptic anterior hypothalamic temperature. Plasma epinephrine values correlated with preoptic anterior hypothalamic temperature for only the controls at 28 degrees C ambient, whereas norepinephrine had significant linear correlation with heat production for all groups and significant negative linear correlation with preoptic anterior hypothalamic temperature. These data indicate norepinephrine may be more important than epinephrine in the maintenance of postburn hypermetabolism in this rat burn model while demonstrating that the hypermetabolism is appropriately responsive to perturbation of preoptic anterior hypothalamic temperature.