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PubMed1997

Involvement of the medial preoptic area in the anorectic action of estrogens.

The implication of the medial preoptic area (MPOA) as a site for estrogen in the regulation of energy balance was investigated. Food intake, O2 consumption (VO2), and CO2 production were measured in ovariectomized rats injected with estradiol (E2) in the medial preoptic nucleus (MPN). Moreover, knowing the potential for corticotropin-releasing factor (CRF) in the anorectic effects of estrogens, we identified estrogen receptors (ER) colocalized in CRF-containing cells of the MPOA and how MPN injections of CRF compared with estrogen injections with respect to VO2 and the VO2-to-CO2 production ratio (respiratory quotient RQ). These energy balance measurements after the injections of four different doses of E2 or CRF were carried out in meal-fed rats chronically implanted with a guide cannula targeted to the MPN. The identification of cells colocalizing ER and CRF was determined using a double-immunostaining procedure revealing ER and CRF immunoreactivities with two different couplers. The injection of E2 into the MPN induced a dose-dependent reduction in food intake, whereas it did not affect VO2 or RQ. Conversely, the injection of CRF into the MPN had no effect on food intake but increased VO2 and decreased RQ. The colocalization of ER and CRF immunoreactivities was found in the MPOA and adjacent regions of the bed nucleus of the stria terminalis. In conclusion, the results of this study provide evidence that the MPOA may represent a potential site for the anorectic effects of E2. Furthermore, the presence of ER and CRF in neurons of the MPOA and adjacent areas suggests a direct interaction between estrogens and the CRF system in the MPOA that is consistent with a role for CRF in the anorectic effects of estrogens. Finally, the results of this study indicate that the effects of a CRF injection into the MPOA differ from those of estrogens, suggesting that if CRF neurons are involved in the anorectic effect of estrogens they likely exert their action outside the MPOA.

Animals↗
PubMed1983

Experimental immunohistochemical studies on the distribution and origins of substance P in the medial preoptic area of the rat.

Distribution of substance P (SP)-positive fibers in the medial preoptic area (POM) of the rat and their origins were examined using indirect immunofluorescence. A very high density of SP-positive fibers was seen in the POM throughout its entire rostro-caudal extent. However, the distribution of these fibers was not even; the highest density was detected in the medial part of the POM, with less dense but still numerous fibers in the lateral part. On the other hand, in this area a small number of SP-positive cells could be found; a few cells were scattered in the rostral part and, in the caudal part, several cells could be seen in the ventral part of the POM. The origins of SP-positive fibers in the POM were experimentally examined. Since the destruction of the ventro-lateral part of the anterior hypothalamus (vlAH), where numerous SP-positive cells were seen, resulted in a marked decrease of SP-positive fibers in the POM on the operated side, the majority of these fibers may originate from SP-positive cells in the vlAH. The fine structure of SP-positive terminals in the POM were investigated by electron-microscopic immunohistochemical techniques. Immunoreactive terminals contained a few large granular vesicles together with numerous small vesicles, and they made synaptic contacts mainly with dendrites which were devoid of immunoreactive materials. Two different synaptic contacts could be distinguished: one asymmetrical (Gray's type I) and the other symmetrical (Gray's type II), with the latter being predominant.

Animals↗
PubMed1997

Modulation of plasma glucose by the medial preoptic area in freely moving rats.

The effect of norepinephrine (NE) injection into the medial preoptic area (MPOA) on plasma glucose was studied in freely moving male rats. The rats were implanted with chronic jugular catheters for blood sampling and with unilateral intracerebral cannulas placed just above the MPOA. Blood samples were taken immediately before and 5, 10, 15, and 30 min after NE injection. As early as 5 min after NE injection, plasma glucose levels rose rapidly, reaching a peak at 15 min poststimulus. The hyperglycemic response to NE injection into the MPOA was dose-related within the range of doses tested (10, 20, and 40 nmol). Previous administration of phentolamine (50 nmol), but not propranolol (100 nmol), into the MPOA blocked the hyperglycemic response to NE injection into the MPOA. The increase of plasma glucose induced by NE into the MPOA and the blockade of the hyperglycemic response to NE by phentolamine suggest the involvement of an alpha-adrenergic mechanism in MPOA-mediated hyperglycemia. On the basis of these and previous results, we propose that MPOA alpha-adrenergic synapses relay impulses activating the sympathetic outflow expressed by neurally mediated hyperglycemia.

Adrenergic Fibers↗
PubMed1997

Effects of medial preoptic area and septal lesions on puberty in female guinea pigs.

Lesions of the medial preoptic area (MPOA) result in the robust display of steroid-induced lordosis by otherwise unresponsive, immature guinea pigs. This study was designed to test the hypothesis that destruction of this region also hastens the onset of ovarian cyclicity, and to ascertain whether lesions of the septum produce effects on puberty similar to those observed following MPOA lesions. Juvenile (13-15 days old), ovariectomized or ovary-intact guinea pigs received bilateral electrolytic or sham lesions of the MPOA or septum. Bilateral lesions of the septum did not influence the display of lordosis or any aspect of estrous cyclicity. However, a higher percentage of guinea pigs with MPOA lesions than with sham lesions displayed progesterone-facilitated lordosis at 22, 29, and 39 days of age; by 49 days of age, the two groups responded in a similar, robust fashion. Females with MPOA lesions were significantly heavier and older than sham-lesioned or nonmanipulated females on the day of first vaginal opening. These data suggest that activity in the MPOA tonically inhibits the display of progesterone-facilitated lordosis through at least 39 days of age but does not suppress the onset of ovarian cyclicity in guinea pigs. Contrary to our hypothesis and in contrast to what has been observed in rats, signals originating in or passing through the MPOA may be required in order for estrous cyclicity to be initiated at the appropriate age. Furthermore, neither of these effects of MPOA lesions appears to be due to damaging efferent or afferent projections through the septum.

Animals↗
PubMed1992

Male rat copulation following 6-OHDA lesions of the medial preoptic area: resistance to repeated administration and rapid behavioral recovery.

Dopamine (DA) in the medial preoptic area (MPOA) has been shown to facilitate male rat sexual behavior. However, injections of the catecholamine (CA) neurotoxin 6-OHDA into the MPOA did not impair copulation in tests 3 days after injection. In the present study, three weekly (serial) injections produced no copulatory deficits compared to animals that received a single injection or to preinjection copulatory behavior scores. However, blocking CA synthesis, which did not impair control rats, produced deficits in both single and serial lesion animals, with significantly fewer serial than single lesion animals initiating copulation. Biochemical analysis of tissue punches showed no difference in MPOA concentrations of dopamine, norepinephrine, epinephrine, or the dopamine metabolite DOPAC between the two groups. Additional animals were tested at earlier intervals after 6-OHDA injections into the MPOA. Tests conducted 30 min after an MPOA injection of 6-OHDA revealed that all measures of copulation were impaired, relative to scores 24 h later. However, these scores were not significantly different from animals tested 30 min after a vehicle injection. A final group, tested 4 h after injection, showed impairment of all measures of copulation compared to vehicle injections and to tests 24 h later. Furthermore, in the tests 24 h later, 6-OHDA animals were not different from vehicle animals. Results from all experiments show that 6-OHDA injections into the MPOA impair copulation for at least 4 h, but that behavioral recovery is complete 24 h later. However, deficits can be reinstated by inhibiting DA synthesis, suggesting that increased synthesis in undamaged terminals contributed to behavioral recovery.

Animals↗
PubMed2005

Attenuation of preoptic area glutamate release correlates with reduced luteinizing hormone secretion in middle-aged female rats.

Glutamate (Glu) and its receptors are involved in the maturation and maintenance of the neural mechanisms governing the preovulatory LH surge of young, reproductive-aged rodents and nonhuman primates. Little is known about the role of Glu in the delayed onset and reduced peak amplitude of the LH surge that characterizes female rodents during early reproductive senescence. The present study tested the hypothesis that the delayed and attenuated LH surge observed in middle-aged female rats is associated with altered hypothalamic Glu release. We used intracerebral microdialysis in young (3-4 months) and middle-aged (9-11 months) female rats to monitor changes in medial preoptic area Glu release and jugular vein catheters to monitor changes in serum LH levels. All animals were ovariectomized and injected with estradiol and progesterone in doses sufficient to produce a robust LH surge in most (approximately 70%) young rats. In both young and middle-aged females that surged, extracellular Glu levels were higher than in those that did not surge. Among animals that surged, the onset of the LH surge was significantly delayed, and the amplitude of the surge was significantly reduced in middle-aged compared with young rats. Middle-aged females also had significantly reduced extracellular Glu levels throughout the day of the LH surge when compared with young females. These data strongly suggest that age-related hypothalamic dysfunction contributes to reproductive aging independent of gonadal failure. We propose that reduced medial preoptic area Glu transmission contributes to reproductive aging by attenuating excitatory input to GnRH neurons.

Aging↗
PubMed1989

Immunohistochemical evidence of the presence of estrogen and progesterone receptors in the same neurons of the guinea pig hypothalamus and preoptic area.

Estrogen and progesterone interact in the regulation of various brain functions including mechanisms controlling gonadotropin secretion and female sexual behavior. Various methods have been used to map the regions where these hormones act and where specific receptors can be detected. However, it remains unknown if both steroids act on the same neuron or if there are neural populations responding to either one or the other of these hormones To answer this question, we used various immunocytochemical procedures to detect estrogen and progesterone receptors (ER-IR and PR-IR) on the same histological section, taking advantage of the fact that anti-ER monoclonal antibodies were raised from rats whereas anti-PR monoclonal antibodies were raised from mice. Initial experiments showed that the number of cells displaying ER and PR immunoreactivity changed with hormonal treatment. Prolonged treatment of ovariectomized guinea pigs with high doses of estradiol benzoate (EB) (10 or 15 micrograms/day for 4 or 6 days) increased the number of PR-positive cells in the preoptic area and the hypothalamus. Inversely, with this estrogen priming regimen the number of ER-positive cells decreased, as did the immunostaining intensity in their nuclei. With a lower dose of estrogen administered for a shorter period (2-microgram dose of EB for 2 days) the two receptor populations could be easily observed. Under these hormonal conditions, the sequential procedure revealed that the vast majority of cells containing ER-IR in the preoptic area (nucleus preopticus periventricularis, medialis) and the mediobasal hypothalamus (nucleus periventricularis, arcuatus, ventrolateral part of nucleus ventromedialis and premamillaris) showed PR immunoreactivity. This was true regardless of the order in which dual immunocytochemical staining was performed. There were, however, a few ER-positive/PR-negative cells in these regions. However, only ER-positive neurons were found in the n. interstitialis stria terminalis, the n. amygdaloideus medialis and the n. supraopticus. Thus, in guinea pigs receiving moderate doses of estrogen, all PR-positive cells contain ER-IR whereas there is a population of ER-positive cells which are devoid of PR-IR.

Animals↗
PubMed1998

C-fos expression pattern in the hypothalamus and the preoptic area of the rat during proestrus.

c-fos gene expression in the hypothalamus, the preoptic area, the hippocampus and the frontal cerebral cortex of the rat was determined every two hours from 09:00 h to 19:00 h on the day of proestrus by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10 h light-dark cycle, with lights on at 06:00 h were used. We found a marked increase in c-fos gene expression in the studied regions but the hippocampus at 13:00 h, followed by a significant diminution in the subsequent hours of proestrus day. The high expression of c-fos gene at 13:00 could be associated to the increase in estradiol seric levels observed both at 11:00 h and at 13:00 h. Our results correlate with the increase in the number of FOS immunoreactive cells in some forebrain areas in proestrus afternoon related to gonadotropin releasing hormone secretion.

Animals↗
PubMed2000

The ability of estradiol to induce Fos expression in a subset of estrogen receptor-alpha-containing neurons in the preoptic area of the ewe depends on reproductive status.

In the ewe, seasonal anestrus results from a change in the hypothalamic responsiveness to estradiol (E2) negative feedback. Considerable evidence has implicated a specific group of dopaminergic neurons (the A15 group) in this seasonally dependent E2 effect, but these neurons do not appear to contain estrogen receptor-alpha (ERalpha). This apparent discrepancy raises the possibility that at least one other neural system is also involved in mediating E2 inhibition. The purpose of this study was to determine whether ERalpha-containing neurons are activated by the negative feedback action of E2 in anestrus. In Exp 1, we examined the effects of E2 on expression of the immediate early gene products, Fos and Fos-related antigens, in ERalpha-positive cells in anestrous ewes. ERalpha and Fos/Fos-related antigens were colocalized using a dual immunofluorescence procedure in sections throughout the hypothalamus from ovariectomized and E2-treated ovariectomized anestrous ewes. A low dose E2 treatment that inhibited LH pulse frequency and induced Fos in A15 dopaminergic neurons in a previous study significantly increased the percentage of ERalpha-containing neurons expressing Fos (17.8% vs. 1.7%) in the medial preoptic area, but not in other hypothalamic areas. In Exp 2, we determined whether there was a seasonal difference in the effect of E2 on Fos/ERalpha colocalization in this region. E2 treatment produced a 3-fold increase in the percentage of ERalpha-positive cells expressing Fos (15.1% vs. 3.4%) in anestrus, but failed to increase ERalpha/Fos colocalization (1.8% vs. 3.5%) during the breeding season. These data raise the possibility that a subset of ERalpha-containing neurons in the medial preoptic area plays a role in the seasonal change in response to E2 negative feedback in the ewe.

Anestrus↗
PubMed1981

[Role of noradrenaline-sensitive neurons of the preoptic area in regulating luteinizing hormone release].

The effect of the microiontophoretic application of noradrenaline to the preoptic area of the hypothalamus on the unit activity and on the plasma and hypophysis LH levels was studied at various stages of estrous cycle. The activatory reaction of the preoptic neurons seems to increase the LH level in the blood. No direct correlation existed between the mode of the unit response to noradrenaline and the LH level changes in hypophysis.

Animals↗
PubMed1986

Acetylcholine rhythm in the preoptic area of the rat hypothalamus is synchronized with the estrous cycle.

Acetylcholine levels in the preoptic area of rat hypothalamus were found to change rhythmically, in synchronization with the estrous cycle. During the proestrous critical period, these levels demonstrated a drop followed by a sharp rise. The absence of this phenomena in males indicates sexual dimorphism. The close association between this newly detected hypothalamic acetylcholine rhythm and the estrous cycle suggests the possible involvement of acetylcholine in regulation of the estrous cycle.

Acetylcholine↗
PubMed1997

Cystic fibrosis mRNA expression in rat brain: cerebral cortex and medial preoptic area.

Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression has been found in the medial preoptic area using in situ hybridization, addressing the possibility of CFTR regulation of sexual maturation and reproductive behaviour. CFTR mRNA has also been found in the cortical deep pyramidal layer V implying possible involvement of CFTR in 'motor' function and output control over bodily movements and secretion. CFTR production in the brain regions observed in this study implicate involvement of CFTR in cerebral control over motor/visceral and endocrine systems.

Animals↗
PubMed2007

Sex differences in projections from preoptic area aromatase cells to the periaqueductal gray in Japanese quail.

In many vertebrate species the medial preoptic area projects to a premotor nucleus, the periaqueductal central gray (PAG). This connection plays an important role in the control of reproductive behavior. In male Japanese quail (Coturnix japonica) specifically, the medial preoptic nucleus (POM), where various types of sensory inputs converge, is a critical site for the activational action of testosterone on male sexual behavior. To activate male copulatory behavior, testosterone must be aromatized to estradiol within the POM and aromatase-immunoreactive cells in the POM are the main source of projections to the PAG. The POM-PAG connection is thus an important functional circuit integrating the sensory with premotor components of sexual behavior. Contrary to what is observed in males, testosterone does not activate male-typical copulatory behavior in females and we investigated here via retrograde tracing methods whether this behavioral sexual difference is associated with a sex difference in connectivity between POM and PAG. Fluorescent microspheres were injected in the PAG of male and female quail and retrogradely labeled fluorescent cells counted in four fields of the POM in sections that had been immunolabeled for aromatase. Males had more aromatase-immunoreactive neurons projecting to the PAG than females and this difference was most prominent in the caudolateral part of the nucleus that has been specifically implicated in the control of male copulatory behavior. These data therefore support the hypothesis that sex differences in POM-PAG connectivity are causally linked to the sex difference in the behavioral response to testosterone.

Analysis of Variance↗
PubMed1995

Effects of chronic alcohol exposure on the morphometric development of medial preoptic area neurons of the male mouse.

We have performed a karyometric study of the medial preoptic area of male mice from mothers that ingested chronically a solution of 20% of ethanol added to the drinking water. Pups then were exposed prenatally to alcohol. After parturition, pups were also exposed to alcohol, first through their mother's milk and after weaning by direct ingestion of the same solution of 20% of alcohol until the day of sacrifice. Animals were sacrificed at the 25th, 35th, 45th, 55th and 100th day and the results compared with those obtained in another group of control animals, sacrificed at the same ages. Chronic alcohol exposure reduces the studied nuclear sizes (perimeter, area and maximum diameter) in adult animals of 100 days of life, but does not produce significative changes in nuclear sizes of younger animals. However, nuclear shape, another of the nuclear parameters analysed, did show significative alterations in relation with the puberal age. These morphometric effects could be due to the reduction of plasmatic testosterone levels produced by alcohol and/or to a direct toxic effect of the alcohol on central nervous system neurons.

Alcohol Drinking↗
PubMed1984

Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats.

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) or with diethylstilbestrol (DES) they became anovulatory and their SDN-POA developed equivalent in size to that of normal males. Identical treatment of male rats resulted in deficient testicular development, but had no influence on SDN-POA volume. The results indicate that the gross morphological sex difference in SDN-POA volume can exclusively be controlled by the hormonal environment during the critical period of sexual brain differentiation, and that non-steroidal estrogens are just as effective as convertible androgens in stimulating SDN-POA differentiation.

Animals↗
PubMed1989

Carbachol injection into the medial preoptic area induces natriuresis, kaliuresis and antidiuresis in rats.

The microinjection of carbachol into the medial preoptic area (MPO) of the rat induced natriuresis, kaliuresis and anti-diuresis in a dose-related manner. Atropine blocked all responses to carbachol. Hexamethonium impaired the dose-response effect of carbachol on kaliuresis, but had no effect on natriuresis and enhanced the antidiuretic effect of carbachol. Nicotine alone had no effects, but pre-treatment with nicotine enhanced the responses to carbachol. These data show that activity of the muscarinic receptors of the MPO increases renal electrolyte and reduces water excretion. They also suggest that nicotinic receptors have an inhibitory effect on water excretion. Nicotine could act through mechanisms unrelated to nicotinic receptors to enhance the effect of the carbachol.

Animals↗
PubMed1990

Effects of medial preoptic area lesions on sleep and wakefulness in unrestrained rats.

Bilateral radiofrequency lesions of the medial preoptic area (MPOA) in unrestrained male rats resulted in a significant decrease in slow wave sleep (SWS) in the light period throughout two postoperative weeks, although the night-active pattern of circadian rhythms was little affected. Both diurnal and nocturnal paradoxical sleep (PS) gradually increased after the lesions. Within one week, however, the daily amount of total sleep (SWS + PS) was recovered to the normal level, since the loss of diurnal SWS was compensated by an increase in nocturnal sleep at the expense of wakefulness. The MPOA lesions brought about a transient elevation of brain temperature, which lasted only for the diurnal period of the day of lesioning. It is speculated that the MPOA plays a definite role in the passage of sleep-regulatory information, especially concerning the circadian distribution of sleep.

Animals↗
PubMed1997

Ventromedial hypothalamus lesions increase the dipsogenic responses and reduce the pressor responses to median preoptic area activation.

In this study, we investigated the participation of adrenergic receptors of the median preoptic area (MnPO) and the participation of ventromedial hypothalamus (VMH) in angiotensin II-(ANG II)-induced water intake and pressor responses. Male rats with sham or electrolytic VMH lesions and a stainless steel cannula implanted into the MnPO were used. Noradrenaline, clonidine (an alpha2-adrenergic receptor agonist), or phenylephrine (an alpha1-adrenergic receptor agonist) injected into the MnPO of sham-lesioned rats reduced water ingestion induced by ANG II injected into the same area. In VMH-lesioned rats ANG II-induced water intake increased with a previous injection of noradrenaline, phenylephrine, or isoproterenol. The pressor response induced by ANG II injected into the MnPO was reduced in VMH-lesioned rats, whereas the pressor response induced by clonidine was abolished. Previous treatment with noradrenaline and phenylephrine into the MnPO of sham-lesioned rats produced a pressor response, and a hypotensive response was obtained with the previous administration of noradrenaline, phenylephrine or isoproterenol into the MnPO of VMH-lesioned rats. These results show that VMH is essential for the dipsogenic and pressor responses induced by adrenergic and angiotensinergic activation of the MnPO in rats.

Adrenergic alpha-Agonists↗