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PubMed1997

Sex differences in estradiol-induced progestin receptor immunoreactivity in the guinea pig preoptic area and hypothalamus.

Progesterone exerts on the central nervous system a number of effects, some of which are estrogen dependent mostly in the preoptic area and the mediobasal hypothalamus. In these regions, an immunocytochemical study was used to evaluate differences in progesterone receptor (PR) immunoreactivity between the male and the female guinea pig in response to 10 micrograms/day estradiol benzoate (EB) for 5 consecutive days. Compared to EB-treated females, EB-treated males showed a slightly lower number of PR-immunoreactive cells in the preoptic area whereas PR-immunoreactivity appeared in more cells in the anterior part of the ventrolateral nucleus. The numbers of PR-immunoreactive cells in the arcuate nucleus did not differ significantly between males and females. These results show that regionally localized sex differences exist in the induced PR system after 5 days exposure to EB.

Animals↗
PubMed1985

The significance of nucleus raphe dorsalis and centralis for thermoafferent signal transmission to the preoptic area of the rat.

Neuronal spike-trains were recorded extracellularly within the preoptic area, which is generally considered the center of information processing for thermoregulation. The neuronal responses were tested by thermal stimulation of the scrotal and abdominal skin of the rat. After a neuron had been identified as warm responsive, electrical stimulation and/or lesion were applied in medial midbrain to test the influence on the preoptic neurons. Post-stimulus-histograms were determined by using 600 single shocks. Furthermore a small area of the medial midbrain was electrolytically lesioned and the thermal response of the neuron was tested again. All lesion, stimulation and recording sites were examined histologically. Electrical stimulation of either nucleus raphe dorsalis or centralis influenced the responsiveness of the recorded preoptic neurons. The post-stimulus-histograms predominantly reveal polysynaptic ascending pathways. Lesion of either nucleus raphe dorsalis or centralis abolished the responsiveness of the recorded preoptic neurons. Lesions lateral to these nuclei were ineffective. By this it is concluded that both nucleus raphe dorsalis and centralis are essentially involved in the thermal signal transmission to the preoptic area.

Afferent Pathways↗
PubMed1999

Oestrogen receptors in the brainstem of the female sheep: relationship to noradrenergic cells and cells projecting to the medial preoptic area.

Oestrogen regulates the secretion of gonadotropin releasing hormone (GnRH) and this could be mediated by noradrenergic systems originating in the brainstem. Whilst it is known that noradrenergic cells possess oestrogen receptors (ER), it is not known whether ER-immunoreactive (-ir) cells in the brainstem project to the regions of the hypothalamus in which GnRH neurons are found. We have used dual-label immunocytochemistry to determine the extent to which ER-alpha is found in noradrenergic cells in the brainstem of the ovariectomized (OVX) ewe. Noradrenergic/adrenergic cells were identified by immunostaining for dopamine beta-hydroxylase (DBH). Cells that stained for both DBH and ER were found in both the A1 and A2 cell groups, with the highest levels found in the most caudal regions. In the A1 group, at the most caudal extent, 73% of ER-ir cells were DBH-positive and 19% of DBH-ir cells were ER-positive. The degree of co-localization decreased in a linear manner towards the rostral brainstem. In the caudal half of A2, 9-14% of ER-ir cells were DBH-positive and 20-25% of DBH cells were ER-positive. Less than 2% of DBH-ir cells in the A5 group were dual-labelled and none of the cells in the A6 and A7 groups were ER-positive. The retrograde tracer FluoroGold was injected into the preoptic area of nine OVX ewes and labelled cells were examined in the brainstem to determine the extent of co-localization of ER. Only injections in the rostroventral part of the medial preoptic area near to the organum vasculosum of the lamina terminalis resulted in the labelling of cells in the brainstem. One ewe with very strong labelling of the brainstem was selected for detailed mapping. In the ventrolateral medulla, half the ER-ir cells in the most caudal regions were retrogradely labelled. Almost all the ER-ir cells in the mid-region of the ventrolateral medulla were retrogradely labelled but no co-localization of retrograde tracer and ER was observed rostral to obex. There were many ER-ir cells and retrogradely-labelled cells in the nucleus of the solitary tract but only a few double-labelled cells. Similarly, numerous ER-ir cells and retrogradely labelled cells were observed around the lateral edges of the caudal fourth ventricle and across to the lateral parabrachial nucleus but there were few double-labelled cells. These results suggest differential regulation of noradrenergic cells by oestrogen, with a direct action of the hormone confined to the cells in the most caudal region of the A1 and A2 cell groups. The cells of the caudal ventrolateral medulla which contain ER-ir cells that project to the preoptic area may be important in the mediation by noradrenaline of the actions of oestrogen on GnRH secretion in the ewe.

Animals↗
PubMed1991

Conditioned place preference produced by infusion of Met-enkephalin into the medial preoptic area.

The conditioned place preference procedure was used to evaluate the rewarding properties of D-Ala2-Met5-enkephalinamide (DALA) after bilateral infusion into the medial preoptic area. Doses of 60, 250 and 100 ng/cannula were used. It was found that all doses of DALA produced place preference. This suggests that the medial preoptic area is a structure where opioid reward is produced in doses as low as those required in already established reward systems. The significance of this in relation to sexual reward is discussed.

Analysis of Variance↗
PubMed1985

Horseradish peroxidase evidence for a spinal projection from the preoptic area of the goldfish, a light and electron microscopic study.

Horseradish peroxidase (HRP) was applied to the transected spinal cord of goldfish labeled neurons in the preoptic area. Since leakage of HRP into the blood could produce the labeling of neurosecretory cells, intraperitoneal (i.p.) injections of HRP were made with a wide range of dosages in order to intentionally label preoptic neurosecretory cells. The distribution of preoptic neurons labeled after spinal HRP application was far more restricted than the labeling via uptake of HRP from the blood, even when cells in the spinal cord-transected fish were intensely labeled. Furthermore, in HRP electron microscopic material, morphological differences were observed between neurons labeled by the two procedures. Large numbers of dense core vesicles and well-developed stacks of rough endoplasmic reticulum, features typical of cells projecting to the pituitary, were not observed in cells labeled via the spinal cord. These findings indicate that in goldfish a direct projection exists from the preoptic area to the spinal cord which could be homologous to one arising from the paraventricular nucleus of mammals. Both i.p. injection and spinal transection also produced labeling of more caudal periventricular diencephalic cells which resemble preoptic cells in efferent projections as well as ultrastructural features.

Animals↗
PubMed1975

Androgen binding proteins in the anterior pituitary, hypothalamus, preoptic area and brain cortex of the rat.

The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of castrated male rats have been found to possess specific androgen binding proteins. The physicochemical characteristics of these binding proteins appear to be very similar. Thus, they were excluded by Sephadex G-100 gel and had a sedimentation coefficient of 6-7S by sucrose gradient centrifugation. The protein nature of the androgen binding components was supported by the fact that protease, but not DNase and RNase eliminated the binding of androgens. In addition, the elimination of the binding by 1 mM p-chloro-mereuriphenylsulfonate (PCMPS) and by heat treatment at 45 C for 30 min indicate that free sulfhydryl groups are necessary for androgen binding and that the proteins are thermolabile. Testosterone, 5alpha-dihydrotestosterone and the antiandrogen Cyproterone acetate were found to possess a much higher affinity than 17beta-estradiol and cortisol for the binding components. Dissociation studies revealed that [3H]testosterone is not easily displaced by unlabeled androgens. In the anterior pituitary, hypothalamus and preoptic area testosterone accounted for the major part of the radioactive material in the total tissue homogenates and also for the greater part of the bound radioactivity 15 min after in vivo administration of [3H]testosterone. [3H]17beta-estradiol accounted for less than 3% of the bound radioactivity under these conditions. If binding of a steroid sex hormone by specific proteins is a prerequisite for the hormonal action, the present study indicates the potential for a direct effect of androgens on the target cells of the anterior pituitary and of the central nervous system

Animals↗
PubMed2004

Sexual dimorphism of GABA release in the medial preoptic area and luteinizing hormone release in gonadectomized estrogen-primed rats.

We showed marked sex differences in the GABA outflow in the medial preoptic area of intact rats. To further determine the sexually dimorphic effects of estrogen on the GABA outflow, an in vivo microdialysis study was performed in gonadectomized rats 3-5 days after the estrogen- or cholesterol-priming. Dialysates and sequential blood samples (150 microl each) were simultaneously collected under freely moving conditions. Serum estradiol concentrations at 72 and 84 h after the estrogen capsule implantation were approximately 75 pg/ml in both sexes. Ovariectomized estrogen-primed (OVX+E(2)) rats showed high GABA outflow from the late night through the morning, which was significantly declined until the onset of surge like secretion of luteinizing hormone (LH) in the afternoon (N=7). Ovariectomized cholesterol-primed (OVX+C) rats consistently showed low GABA outflow and high serum LH concentration (N=8). Conversely, orchidectomized estrogen-primed (ORX+E(2)) rats showed high and episodic GABA outflow without any daily changes (N=7), which was significantly greater than orchidectomized cholesterol-primed (ORX+C; N=8) and OVX+C rats. Only OVX+E(2) rats showed significant daily changes in the GABA outflow and serum LH concentration. Fitting with the double cosinor method demonstrated that the acrophase of the GABA outflow in OVX+E(2) rats occurs in the early morning, whereas the acrophases in OVX+C, ORX+C, and ORX+E(2) rats occur at various times of day. The present findings suggest that sex-specific effects of estrogen on the daily GABA release in the medial preoptic area may be involved in the sex difference of LH release in rats.

Animals↗
PubMed1983

Maturation of the goldfish preoptic area: ultrastructural correlates of position and maturation of neurosecretory cells.

A gradation of small rostral to larger caudal neurosecretory cells is found in the preoptic area of fish. Regional variations in ultrastructural features were assessed in this region of fish ranging widely in size (1.7-283.1 g), some of which had received intraperitoneal injections of horseradish peroxidase in order to label neurons projecting beyond the blood-brain barrier (i.e. neurosecretory cells). In small (less than or equal to 6.6 g) fish, neurosecretory cells of the caudal preoptic area were 10-15 microns in diameter and contained dense core vesicles. More rostral smaller cells had few or no dense core vesicles, but were labeled following intraperitoneal horseradish peroxidase injections. Cells in both areas were progressively larger, with larger nuclei and more granular reticulum in larger fish. In large fish, neurons that contained dense core vesicles ranged from 10 microns in diameter rostrally to 70 microns in diameter caudally. Some intermediate and large cells were extensively vacuolated and contained extremely convoluted and possibly multiple nuclei. Degenerating material was seen in apparently normal large fish. A few neurosecretory cells were extensively surrounded by perineuronal electron-dense glial cells. Most neurosecretory cells were involved in extensive soma-somatic apposition, which was especially pronounced in fish which were removed from cold water in late fall. Gap junctions were also clearly present on the somata of preoptic neurosecretory cells of these fall fish. These data imply that increased capacity for hormone secretion in large fish may be accomplished in part by neuronal hypertrophy. Maturational and seasonal variation in structure suggest that physiological characteristics are also variable in this nucleus.

Animals↗
PubMed1986

Evidence that serotonin is involved in the sexually dimorphic development of the preoptic area in the rat brain.

To investigate the possibility that serotonin plays a role in the sexually dimorphic development of a nucleus in the medial preoptic area of the rat brain, p-chlorophenylalanine, an inhibitor of serotonin biosynthesis, was administered to pregnant dams from day 8 of gestation until parturition. This treatment did not alter plasma steroid levels but increased the volume of the sexually dimorphic nucleus in female neonates to that of control males. Thus, serotonin is implicated as a neurochemical which may be involved in the sexually dimorphic development of the preoptic area.

Animals↗
PubMed1984

The sexually dimorphic region of the preoptic area in rats contains denser opiate receptor binding sites in females.

Quantitative autoradiographic analysis of opiate receptor binding using [3H]naloxone shows higher levels in the sexually dimorphic region of the medial preoptic area in female rats than in males. Opiate receptor density varies across the estrous cycle being densest in diestrous females. The sexually dimorphic nucleus of the preoptic area lies within the opiate receptor-rich region. Endogenous opiates in the medial preoptic region acting at opiate receptors which are of differential density in males and females could influence sex-specific behavior mediated by the region.

Animals↗
PubMed1988

Cold-induced free fatty acid mobilization is impaired in rats with lesions in the preoptic area.

The increase in plasma free fatty acids (FFA) induced by cold (2 h at 5 degrees C) in rats with bilateral electrolytic lesions in the preoptic area was reduced to 30% compared to sham-operated controls. Blood glucose of lesioned rats increased 35% over initial levels and remained elevated, whereas in controls it returned to initial levels after 2 h. Rectal temperature decreased 3 degrees C in lesioned rats but not in controls. These data demonstrate the participation of the preoptic area in cold-induced FFA mobilization and provide evidence for the role of this area in the integration of thermal inputs with energy-linked metabolic processes.

Acclimatization↗
PubMed1994

Developmental profile of estrogen receptor mRNA in the preoptic area of male and female neonatal rats.

Exposure to estrogen or estrogenic metabolites of testosterone during the early postnatal period has permanent effects on rodent brain development. Differential sensitivity to estrogen, as reflected by transcription of the estrogen receptor gene, might determine the period of maximal sensitivity to the masculinizing effects of estrogen. We used an 35S-labeled riboprobe and in situ hybridization to chart the development of estrogen receptor (ER) mRNA expression in the rat preoptic area, a brain region for which sexual dimorphisms and the effects of estrogen on development are particularly well documented. Neonatal male and female rats were sacrificed by perfusion fixation on postnatal days 0, 2, 4, 7 or 10 (PND; day of birth is PND 0). Many ER mRNA-containing cells were detected in the periventricular preoptic area and medical preoptic nucleus and the distribution of ER-synthesizing cells was similar in both sexes. Analysis of film autoradiograms showed that the relative steady state level of ER mRNA was significantly higher in females than in males at all ages except PND 0 and 10. The temporal profile of ER mRNA expression was different in males and females. ER mRNA did not change with age in males, whereas in females, ER mRNA was significantly higher on PND 2 compared with PND 0 and 10. These results demonstrate that the pattern of ER mRNA expression is quantitatively and qualitatively different between the sexes during the neonatal period. The pattern of ER mRNA expression contrasts markedly with previous reports of estrogen binding based on biochemical and autoradiographic steroid binding assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Differential ICP responses elicited by electrical stimulation of medial preoptic area.

Recent findings indicate a complex role for the medial preoptic area (MPOA) in modulating penile erection. To further investigate this important area we measured changes in intracavernous pressure (ICP) elicited by electrical stimulation of the MPOA and evaluated the contribution of the cavernous nerve to the ICP responses after bilateral transection of the cavernous nerve (CN). In all experiments electrical stimulation was performed unilaterally in anesthetized male rats. Two distinct patterns of ICP response were seen after electrical stimulation of the MPOA: 1) increases in ICP during electrical stimulation (pattern 1, n = 10 rats) and 2) increases in ICP after electrical stimulation was terminated (pattern 2, n = 10 rats). For pattern 1, increases in ICP during stimulation exhibited a stable plateau without contraction of striated penile muscles, and bilateral transection of the CN eliminated the ICP responses. For pattern 2, increases in ICP observed after stimulation were lower, more variable, and accompanied by significant amplitude variations ("peaks"), caused by contraction of striated penile muscles. Bilateral transection of the CN eliminated the pattern 2 ICP response but did not alter striated muscle contraction. Histological studies documented that pattern 1 and pattern 2 responses occurred via electrical stimulation of the anterior and posterior areas of the MPOA, respectively. Thus both responses appear to result from activation of the CN, but the pattern 2 response apparently involves contraction of the striated penile muscles as well.

Animals↗
PubMed1976

Immunoreactive luteinizing hormone releasing factor in rat pituitary stalk blood: effects of electrical stimulation of the medial preoptic area.

Blood was collected from the cut pituitary stalk of male and female rats before and during the application of an electrical stimulus to the medial preoptic area. The plasma was assayed for immunoreactive LH releasing factor (RF) by a double antibody radioimmunoassay using a specific antiserum raised in rabbits against the free acid derivative of the decapeptide LH-RF conjugated to bovine serum albumin. The decapeptide (used as a standard) and pituitary stalk plasma cross-reacted in a similar manner with the antiserum. Stimulation of the preoptic area increased significantly the amount of LH-RF in pituitary stalk plasma in both male and female rats. The increase in LH-RF was linearly related to the strength of the stimulating current, and the amount of LH-RF liberated diminished on cessation of the stimulus. The concentration of LH-RF in pituitary stalk plasma from female rats was significantly greater than that in jugular venous plasma. The magnitudes of the mean increments of LH-RF in pituitary stalk plasma (stimulation minus pre-stimulation values) at various times of the oestrous cycle in female rats suggest that between 18.00 h of dioestrus and 13.00 h of pro-oestrus there is an increase in sensitivity of the LH-RF secretory mechanism to electrical stimulation. However, the increments decreased in magnitude between 13.00 and 18.00 h of pro-oestrus, indicating that the marked increase in responsiveness of the hypothalamo-hypophysial system to electrical stimulation which occurs during this period is due mainly to a change in sensitivity of the pituitary gonadotrophs to LH-RF. The LH-RF in pituitary stalk plasma collected before application of the stimulus was higher at some of the times examined during pro-oestrus than at other times of the oestrous cycle. A higher level of the secretion of the factor may be important for the full development of the priming effect of LH-RF and, consequently, the marked increase in responsiveness of the pituitary gland which occurs during the afternoon of pro-oestrus.

Animals↗
PubMed1983

Lesions of the medial preoptic area prevent the facilitation of maternal behavior produced by amygdala lesions.

In the present study we tested the hypothesis that the facilitation of maternal behavior produced by amygdala lesions is mediated through the medial preoptic area. Different groups of animals sustained lesions of the corticomedial amygdala (Group AM), the medial preoptic area (Group MPOA), both regions (Group AM-MPOA), the corticomedial amygdala and non MPOA control sites (Group AM-CX), and control sites (Groups LC or SC). Animals were tested for their maternal responses to foster pups presented daily for an 11 day period. It was found that groups sustaining lesions of the amygdala (Group AM and AM-CX) became maternal more rapidly than did Control Groups (LC and SC), Group MPOA, and Group AM-POA. However, animals in Group AM-POA were similar to Groups AM and AM-CX in that they did not avoid pups, whereas groups not sustaining lesions of the amygdala did. These results, taken together, suggest that amygdala-induced facilitation of maternal behavior in the nulliparous females is mediated through the MPOA. They suggest, moreover, the primary effect of removing the amygdala is to reduce avoidance of pups, with only secondary effects on maternal responsiveness.

Amygdala↗
PubMed1991

Effect of testosterone replacement on the alteration of steroid metabolism in the hypothalamic-preoptic area of male hamsters treated with melatonin.

Adult male hamsters were maintained under 14 hours of light per day and randomly assigned to groups that received daily afternoon melatonin (25 micrograms) or vehicle injections. Animals from both groups were killed following 4, 8, and 12 weeks of treatment. By 12 weeks, the melatonin-treated hamsters had significant reductions in the weights of the testes and seminal vesicles, serum testosterone levels, and activities did not differ between groups. In a second experiment, hamsters were hypothalamic-preoptic area (HPOA) aromatase activities. Hypothalamic-preoptic area 5 alpha-reductase activities did not differ between groups. In a second experiment, hamsters were again treated with melatonin or vehicle for 12 weeks prior to being killed. After 10 weeks of treatment, groups of melatonin-treated animals received subcutaneous silastic capsules (5, 10, or 20 mm) filled with testosterone. Animals in two other groups were given blank implants or no implants at all. Two weeks later, at autopsy, reproductive organ weights, serum testosterone levels, and HPOA aromatase activities were significantly suppressed by melatonin administration. 5 alpha-Reductase activity in the HPOA was not affected. Hamsters that had been given the 10- and 20-mm testosterone implants exhibited normal seminal vesicle weights and HPOA aromatase activities. These results suggest that melatonin-induced reduction of HPOA aromatase activity is mediated by decreased circulating levels of testosterone.

Animals↗
PubMed1987

Implantation of fetal preoptic area into the lateral ventricle of adult hypogonadal mutant mice: the pattern of gonadotropin-releasing hormone axonal outgrowth into the host brain.

Transplantation of fetal preoptic area tissue containing gonadotropin-releasing hormone neurons into the third ventricle of male hypogonadal mice resulted in an elevation of pituitary gonadotropin levels and correction of hypogonadism. This reversal of the neuroendocrine deficit was correlated with innervation of the median eminence by gonadotropin-releasing hormone axons. The specificity of fiber outgrowth suggested that local neuromodulatory factors might guide these axons to the nearby median eminence. To test this hypothesis, 14 adult hypogonadal males received unilateral fetal preoptic area grafts into the lateral ventricle, a site distant from the median eminence. After four months, healthy grafts containing numerous gonadotropin-releasing hormone neurons were seen in 9 hosts. However, none of these grafts corrected the hypogonadism of the host and there was no gonadotropin-releasing hormone innervation of the median eminence in any of these animals, thus demonstrating that the presence of gonadotropin-releasing hormone neurons in the ventricular space is itself not sufficient to stimulate the pituitary-gonadal axis. Instead, gonadotropin-releasing hormone axons coursed in the host fimbria, fornix, corpus callosum, and stria terminalis. These fibers could be traced into the anterior hippocampal area, medial and lateral septum, and the anterior hypothalamus. The distribution of these fibers included a number of regions which receive gonadotropin-releasing hormone fiber input in the normal mouse. These findings show that gonadotropin-releasing hormone neurons transplanted into the lateral ventricle can survive and extend processes into the host brain, often projecting to sites of normal gonadotropin-releasing hormone innervation. Their success in contacting these sites suggests that gonadotropin-releasing hormone fiber outgrowth may be influenced by regionally specified trophic and/or guidance factors.

Animals↗