Hypothalamus Of Female Rats Research Articles

Prepubertal chronic ethanol administration alters TTF-1 and Oct-2 expression in the hypothalamus of female rats

We found that prolonged administration of ethanol (3 g/kg i.p. at 08:00, once per day) to young female rats starting on postnatal day 24 caused delayed puberty. We further found that prolonged ethanol administration changed the typical hypothalamic expression patterns of TTF-1 and Oct-2 and reduced GnRH mRNA expression. We suggest that these changes may cause the ethanol-induced disturbances in the regulation of GnRH in the hypothalamus and may be responsible for the ethanol-induced reduction in GnRH and LH associated with delayed puberty.

Differential effects of reproductive and hormonal state on basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity in the hypothalamus and cingulate cortex of female rats

Morphological changes in astrocytes occur in a number of brain regions including the hypothalamus and hippocampal regions as a function of hormonal and reproductive state. Because basic fibroblast growth factor has been shown to play an important role in morphological changes in astrocytes, we investigated whether basic fibroblast growth factor immunoreactivity would also be influenced by reproductive state and circulating gonadal steroids. To do this we compared astrocytic basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity in hypothalamic nuclei and the cingulate cortex, area 2 among groups of cycling, late pregnant and lactating rats as well as in ovariectomized and ovariectomized hormone-replaced females. Significant differences in both basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity were observed across groups in the supraoptic nucleus, parvocellular paraventricular nucleus, medial preoptic area of the hypothalamus and cingulate cortex 2. The pattern of change in basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity varied across regions both in direction and magnitude. For example, although in the supraoptic nucleus ovariectomized rats had lower levels of basic fibroblast growth factor-ir than cycling females, this pattern was reversed within cingulate cortex. Overall the results of this study suggest that reproductive and hormonal states are associated with robust changes in basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity in a number of brain areas but that the changes observed vary in magnitude as well as direction from one brain region to another.

Estradiol Protects Against Oxidative Stress Induced by Chronic Variate Stress

Neurochemical gender-specific effects have been observed following chronic stress. The aim of this study was to verify the effects of chronic variable stress on free radical production (evaluated by DCF test), lipoperoxidation (evaluated by TBARS levels), and total antioxidant reactivity (TAR) in three distinct structures of brain: hippocampus, cerebral cortex and hypothalamus of female rats, and to evaluate whether the replacement with estradiol in female rats exerts neuroprotection against oxidative stress. Results demonstrate that chronic stress had a structure-specific effect upon lipid peroxidation, since TBARS increased in hypothalamus homogenates of stressed animals, without alterations in the other structures analyzed. Estradiol replacement was able to counteract this effect. In hippocampus, estradiol induced a significant increase in TAR. No differences in DCF levels were observed. In conclusion, the hypothalamus is more susceptible to oxidative stress in female rats submitted to chronic variable stress, and this effect is prevented by estradiol treatment.

Orexin A and B levels in the hypothalamus of female rats: the effects of the estrous cycle and age.

Orexins have been implicated in the regulation of several physiological functions including reproduction, energy balance and vigilance state. For successful reproduction, the precisely timed hormonal secretions of the estrous cycle must be combined with appropriate nutritional and vigilance states. The steroid- and nutritional state-dependent modulation of LH release by orexins, as well as an increase of vigilance, suggest that orexins may co-ordinate these functions in the course of the estrous cycle. We studied the brain tissue levels of orexins in the course of the estrous cycle in young and middle-aged rats. Young cycling rats (3 months old) and irregularly/non-cycling (7-9 months old) female rats were inspected for vaginal smears and serum hormone levels. Tissue concentrations of orexin A and B were measured in the hypothalamus and lateral hypothalamus on different days of the estrous cycle. Orexin A concentration in the hypothalamus of young cycling rats was higher on the day of proestrus 5-6 h after the lights were switched on than on the other days of the estrous cycle at the same circadian time. Orexin B concentration was higher on both the day of proestrus and the day of estrus as compared with the days of diestrus. The hypothalamic concentrations of both orexin A and B in the non-cycling middle-aged rats were lower than those in cycling rats on the days of proestrus and estrus. We have concluded that the high hypothalamic concentration of orexins on the day of proestrus may contribute to the LH and prolactin surges. High orexin A levels may also contribute to the decreased amount of sleep on the day of proestrus.

Expression of proopiomelanocortin and proenkephalin mRNA in sexually dimorphic brain regions are altered in adult male and female rats treated prenatally with morphine.

The present study demonstrates that prenatal morphine exposure on gestation days 11-18 differentially alters proopiomelanocortin (POMC) and proenkephalin (pENK) mRNA in the hypothalamus and limbic system of adult male and female rats. In adult, prenatally morphine-exposed male rats POMC mRNA levels are decreased in the arcuate nucleus of the hypothalamus (ARC), while the pENK mRNA levels are increased in the paraventricular nucleus of the hypothalamus (PVN) and in the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), specifically in the ventrolateral subdivision of the VMH. In adult, prenatally morphine-exposed female rats, POMC mRNA levels in the ARC are increased in ovariectomized (OVX) but not in OVX, estradiol benzoate- (EB) or EB- and progesterone- (P) treated females. In contrast, pENK mRNA levels are decreased in the VMH of morphine-exposed, OVX females and increased in EB-treated females. Further, prenatal morphine exposure decreases pENK mRNA in the ARC and increases it in the medial pre-optic area independently of female gonadal hormones. Finally, POMC mRNA levels are increased in the ARC of saline-exposed, EB- or EB- and P-treated females but not in OVX females. Thus, the present study suggests that prenatal morphine exposure sex and brain region specifically alters the level of POMC and pENK mRNA.

Regulation of estrogen receptor-beta expression in the female rat hypothalamus: differential effects of dexamethasone and estradiol.

Estrogen and glucocorticoids interact in multiple aspects of endocrine regulation by exerting opposing influences on the expression of selective genes. In rats, estrogen receptor (ER)-beta is the predominant form of ER present in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, suggesting its involvement in neuroendocrine regulation. To date, the hormonal regulatory profile of the ERbeta gene in the rat central nervous system has not been closely elucidated. In the present study, we first examined the effects of dexamethasone (DEX) and estradiol benzoate (EB) on the ERbeta protein expression in the PVN and SON of ovariectomized female rats. In the SON and parvocellular and magnocellular parts of the PVN, the number of ERbeta immunoreactive nuclei significantly increased after DEX treatment, compared with the control group, whereas EB treatment caused a significant decrease. The effect of EB was consistent across other brain nuclei such as the anteroventral periventricular nucleus and medial preoptic nucleus. To determine the molecular level at which DEX and EB control ERbeta expression, we examined the effects of these steroids on ERbeta mRNA levels using real-time RT-PCR. EB significantly decreased the expression of ERbeta mRNA in the PVN (P = 0.0006) and SON (P < 0.01). In contrast, DEX did not change ERbeta mRNA levels. These results indicate that glucocorticoids and estrogen exert opposing regulatory influences on the ERbeta gene expression. This may represent a mechanism by which these steroids can alter the cellular sensitivity of ERbeta-expressing neurons to subsequent steroidal activation.

Estradiol and progesterone modulate the nitric oxide/cyclic gmp pathway in the hypothalamus of female rats and in GT1-1 cells.

Considerable evidence suggests that the nitric oxide (NO)/cGMP signaling pathway plays an important role in the expression of reproductive behavior and in gonadotropin-releasing hormone (GnRH) release from the hypothalamus The effects of the NO/cGMP pathway on GnRH release and gene expression have also been examined in GT1 cells. However, it is still controversial whether NO/cGMP signaling facilitates or inhibits GnRH release in these cells. The current study examined the effects of estradiol and progesterone on neuronal NO synthase (nNOS), soluble guanylyl cyclase (sGC), and NO-dependent cGMP production in the preoptic area (POA) and hypothalamus (HYP) as well as in GT1-1 cells. Ovariectomized female rats received vehicle, estradiol benzoate (48 h) and/or progesterone (3-4 h) before preparation of brain slices. GT1-1 cells were incubated with vehicle, estradiol (48 h), progesterone (3-4 h), or with both hormones. The combination of estradiol and progesterone increased the expression of nNOS protein in the POA and HYP. Hormones had little effect on the abundance of sGC. Estradiol and progesterone together greatly enhanced NO-stimulated sGC activity in HYP-POA slices. In GT1-1 cells, NO-stimulated sGC activity was significantly increased by estradiol and progesterone, alone or in combination, but sGC expression was not altered by hormones.

Leptin receptors are developmentally regulated in rat pituitary and hypothalamus

We have previously reported that leptin is expressed in adult rat brain and pituitary gland, though the role of leptin in these sites has not been determined. Leptin mRNA is developmentally regulated in the brain and pituitary of male and female rats during early postnatal development, suggesting a role in the maturation of the brain-pituitary system. Here, we sought to extend our previous studies by evaluating (1) the ontogeny of leptin receptor mRNA levels in rat brain and pituitary and (2) pituitary leptin protein levels in neonatal and pre-pubertal rats. Pituitary leptin concentration was highest shortly after birth (postnatal day (PD) 4, 25 ng/mg protein) and fell significantly throughout postnatal development and into adulthood (PD 60, 3.5 ng/mg protein; P<0.005) coincident with a decline in pituitary leptin mRNA levels. Significant age-related effects on leptin receptor mRNA levels were also observed in the pituitary and the hypothalamus of male and female rats using semi-quantitative RT-PCR analysis. In the pituitary, the short form (OBRa) mRNA levels were highest in neonatal rats (PD 4) but declined throughout postnatal development (PD 4–22) paralleling the fall in pituitary leptin mRNA and protein levels. The long form (OBRb) mRNA levels were unaffected by age between PD 4 and 22. In contrast, hypothalamic, levels of OBRb mRNA were very low to undetectable shortly after birth (PD 4) and rose significantly between PD 4 and 14/22 while levels of OBRa mRNA were not significantly different between PD 4 and 22. Immunohistochemical detection of leptin receptor immunoreactivity (all forms) revealed the presence of OBR-like protein in pituitary and hypothalamus as early as PD 4. Cortical leptin receptor mRNA levels were similar throughout early postnatal development. No gender-related differences in leptin receptor mRNA levels were noted in brain or pituitary. In conclusion, these data, together with our previous work, indicate that the neonatal pituitary gland expresses leptin and leptin receptors at levels far in excess of those observed in mature rats. The pituitary is thus quite different from adipose tissue, hypothalamus and cerebral cortex, in which neonatal leptin expression is lowest at birth. Since neonatal pituitary leptin receptor expression is also elevated, it is possible that pituitary-derived leptin plays some role in the development of the hypothalamic-pituitary system.

Distribution of androgen-binding protein in the rat hypothalamo-neurohypophyseal system, co-localization with oxytocin

Androgen-binding protein (ABP) is known to be expressed in the male and female rat hypothalamus. In the present study, we observed immunocytochemically ABP in neurons of the magnocellular hypothalamic nuclei, in the preoptic region and in the lateral hypothalamus. Dense fiber networks with varicosities, containing ABP immunofluorescence, were visible throughout the hypothalamus, the median eminence and in the posterior pituitary lobe. Double immunostaining revealed a partial coexistence of ABP—and oxytocin immunoreactivity in a portion of the magnocellular perikarya. ABP was isolated by affinity chromatography from hypothalamus homogenates. Western blots resulted in immunoreactive (IR) bands with an approximate molecular weight of 35 and 50 kDa. Mass spectrometry of these preparations confirmed the presence of ABP, which was almost identical to ABP isolated from rat testis. It is likely that ABP, expressed in magnocellular oxytocinergic neurons, is subject to axonal transport and release in the hypothalamo-neurohypophyseal system.

Immediate and residual effects of tamoxifen and ethynylestradiol in the female rat hypothalamus

Very little is known about the impact of selective estrogen receptor modulators (SERMs) on the brain. We examined the effects of tamoxifen (TAMOX) and the synthetic estrogen 17α-ethynylestradiol (EE) on estrogen-dependent gene expression and receptor binding in the female rat brain. Both immediate and residual effects were examined in both the presence and absence of 17β-estradiol. Two groups of adult, ovariectomized, female rats ( n=30 per group) were injected with TAMOX (5 mg/kg), EE (0.1 mg/kg), or sesame oil daily for 14 days. Animals from the first group were implanted with blank or 17β-estradiol Silastic capsules concurrently with the last three SERM injections (immediate, group 1). Animals from the second group received either blank or 17β-estradiol implants 2 weeks after the last injection (residual, group 2). All animals were sacrificed 72 h after implantation. TAMOX increased uterine weight in the absence of estrogen, but inhibited uterine weight gain in the presence of estrogen in both groups 1 and 2. TAMOX and EE increased oxytocin receptor binding in the ventromedial nucleus of the hypothalamus (VMN) in the absence of estrogen in both groups 1 and 2. The estrogen-dependent induction of PR mRNA expression in the VMN was significantly attenuated by TAMOX in group 1. Finally, TAMOX and EE had opposite effects on ERβ mRNA expression in the paraventricular nucleus in the absence of 17β-estradiol in group 1. Neither had any effect in group 2 when 17β-estradiol was present. These results suggest that TAMOX has mixed agonist/antagonist effects in the female rat brain, many of which persist at least 2 weeks after the administration ceases.

Colocalization and hormone regulation of estrogen receptor alpha and N-methyl-D-aspartate receptor in the hypothalamus of female rats.

Effects of N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation on neuroendocrine function can be modulated by the steroid hormone milieu. For example, the hypothalamic GnRH neurons, the primary cells regulating reproductive function, are stimulated by NMDAR agonists, and this is greatly potentiated by estrogen. We hypothesized that the actions of glutamate and estrogen may converge at target cells in the brain in which the NMDA and estrogen receptors (ERs) are coexpressed. To this end, we used quantitative stereological techniques to determine the colocalization of the obligatory NMDAR subunit, NR1, and the ERalpha, in the anteroventral periventricular nucleus and the medial preoptic nucleus, two critical regions for reproductive physiology and behavior. We observed extensive colocalization of ERalpha and NR1 in these brain regions (approximately 80%). In the anteroventral periventricular nucleus, treatment of ovariectomized rats with estrogen up-regulated the coexpression, whereas in the medial preoptic nucleus, estrogen had no effect, demonstrating a regional specificity to the estrogen sensitivity. The number of ERalpha cells that did not express NR1 was not altered by estrogen treatment in either brain region. Thus, we speculate that the extensive colocalization of ERalpha and the NMDAR provides an anatomical level at which estrogen and glutamate can act at target cells, and potentially synergize, to influence neuroendocrine and autonomic functions.

Variation in the expression of orexin and orexin receptors in the rat hypothalamus during the estrous cycle, pregnancy, parturition, and lactation.

The widespread distribution of mRNA encoding orexin- 1 (OX1R) and -2 receptors (OX2R) in the central nervous system suggests that orexin may be involved in multiple functional pathways. Central administration of orexin stimulates feeding and also affects ovarian steroid-dependent luteinizing hormone secretion, suggesting involvement of orexin in the regulation of reproductive function. To investigate a possible role for orexin in reproductive function, we examined variations in prepro-OX, OX1R, and OX2R mRNA levels in the female rat hypothalamus during the estrous cycle, pregnancy, parturition, and lactation using competitive reverse transcription-polymerase chain reaction. During the estrous cycle, only OX1R mRNA expression during late proestrus was significantly higher than that at metestrus. The prepro-OX and OX1R mRNA levels on d 1 of lactation were significantly higher than that during late pregnancy and lactation. Immunohistochemistry revealed the presence of orexin-A immunoreactive cells and the OX1R subtype in the lateral hypothalamic area as well as the magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei, respectively, in pregnant and lactating rats. These results suggest a role for orexin in reproduction that may be involved in regulating physiological function in early lactation through important binding sites in hypothalamic PVN and SON.

Glucoprivation-induced Fos expression in the hypothalamus and medulla oblongata in female rats.

Glucoprivation induced by 2-deoxy-D-glucose (2DG) suppresses pulsatile luteinizing hormone (LH) secretion in female rats. The suppression is enhanced in the presence of estrogen. In the present study, 2DG-induced Fos expression was examined in the solitary tract nucleus (NTS), hypothalamic paraventricular nucleus (PVN), raphe obscurus nucleus (ROb) and raphe pallidus nucleus (RPa), which have been previously suggested to be involved in glucoprivation-induced suppression of LH secretion in female rats. Ovariectomized (OVX) or estrogen-primed ovariectomized (OVX+E(2)) rats were injected intravenously with 2DG (400 mg/kg BW). The brain was removed 1 h after the injection. The number of Fos-like-immunoreactive (Fos-li) cells in the PVN and NTS was significantly increased in OVX+E(2) rats compared with control groups, but did not show a significant increase in the OVX group. Few Fos-li cells were observed in the ROb and RPa in all groups. All of the Fos-li cells in the PVN and NTS were neurons because they had immunoreactivities to microtubule-associated protein 2. Some Fos-li cells (8.3%) had tyrosine hydroxylase-like immunoreactivities in the NTS in 2DG-treated OVX+E(2) rats. These results suggest that neurons in the PVN and NTS are involved in the estrogen-dependent neural cascade mediating glucoprivic suppression of LH secretion in female rats.

GnRH-immunoreactive fiber changes with unilateral amygdala-kindled seizures

Purpose: To assess whether unilateral amygdala seizures are associated with a change in the number and lateral distribution of gonadotropin releasing hormone (GnRH)-staining fibers in the ventromedial hypothalamus of female rats. Methods: The study compared three groups of female rats: (1) amygdala seizures induced by focal injection of kainic acid (KA); (2) saline injected controls; and (3) naı̈ve controls. The animals were sacrificed at 4 weeks in the diestrus phase. GnRH fibers were counted in the ventromedial hypothalamus and compared among groups. Results: GnRH fiber counts were significantly lower in KA than saline and naı̈ve animals ipsilaterally but not contralaterally. Conclusions: This finding may support a potential mechanism by which (1) temporolimbic epilepsy may promote the development of reproductive endocrine disorders and (2) the laterality of the epilepsy may influence the particular nature of the reproductive endocrine disorder.

Correlation of estrogen β-receptor messenger RNA with endogenous levels of plasma estradiol and progesterone in the female rat hypothalamus, the bed nucleus of stria terminalis and the medial amygdala

Estrogen receptor β (ERβ) has been previously mapped in the rat central nervous system. This study aims to explore the regulation of ERβ mRNA as it is expressed in the intact and cycling female rat brain. Young adult female rats (90+ day, N=20) were screened for estrous phases via vaginal cytology and sacrificed. Brains and blood were collected and processed for in situ hybridization and estradiol (E2) and progesterone (P4) hormone assays, respectively. ERβ mRNA levels exhibited significant correlations with ovarian steroid ratios (E2/P4) in various brain regions, including the bed nucleus of stria terminalis, the medial nucleus of amygdala, and the anteroventral periventricular nuclei but not the paraventricular and the supraoptic nuclei or the preoptic area of the hypothalamus. No regulatory changes were detected in the cortex. Specifically, in the affected regions, higher P4 levels were significantly correlated with higher ERβ mRNA expression. In contrast, there was a tendency for higher E2 levels to be correlated with lower ERβ mRNA expression, but this tendency reached significance only in the bed nucleus of stria terminalis. These results suggest that ERβ mRNA is regulated in the intact and cycling female rat hypothalamic as well as extrahypothalamic brain regions, and the circulating ovarian hormones play a critical role.

Expression of the nuclear receptor coactivator, cAMP response element-binding protein, is sexually dimorphic and modulates sexual differentiation of neonatal rat brain.

Recent studies indicate that the transcriptional activity of steroid receptors is governed by proteins called nuclear receptor coactivators. Using immunocytochemistry, we found that on the day of birth (postnatal d 0) males express higher levels of the nuclear receptor coactivator, cAMP response element binding protein-binding protein (CBP), within the ventromedial hypothalamus, medial preoptic area, and arcuate nucleus. Using Western immunoblots, we confirmed that males have higher levels of CBP on postnatal d 0, 1, and 5; however, there was no sex difference on postnatal d 11. To examine the functional role of CBP, we infused oligodeoxynucleotides that were antisense to CBP mRNA or a scrambled sequence as a control into the hypothalamus of female rats on postnatal d 0, 1, and 2. On postnatal d 1, all rats were injected with 100 microg testosterone propionate to both masculinize (increase male) and defeminize (decrease female) sexual behavior. Rats were ovariectomized in adulthood and tested for adult sexual behavior. Neonatal CBP antisense oligodeoxynucleotides treatment interfered with the defeminizing, but not the masculinizing, actions of testosterone. These results indicate that CBP expression in developing rat brain is sexually dimorphic and an important modulator for steroid hormone action.

Regulation by Gonadal Steroids of the mRNA Encoding for a Type I Receptor for TGF-β in the Female Rat Hypothalamus

We have recently shown that the mRNA encoding for a type I receptor for transforming growth factor beta and activin – named B1 – is expressed in hypothalamic areas implicated in gonadotropin-releasing hormone regulation, particularly in estrogen-receptive regions. In the present study, we examined whether ovarian steroids may regulate expression of B1 mRNA in the hypothalamus. Comparing relative levels of B1 mRNA expression in ovariectomized (OVX), OVX + estradiol-treated, and OVX + estradiol + progesterone-treated female rats, we observed that estrogen significantly (p < 0.05) downregulated B1 mRNA levels in the anteroventral periventricular nucleus (by 12.5%), medial preoptic nucleus (by 27.5%), and arcuate nucleus (by 29.5%). In contrast, no effects of gonadal steroids were observed in the median preoptic nucleus. We next examined whether cells expressing B1 mRNA may be direct targets for the action of estrogen. Using an in situ hybridization coupled to immunohistochemical labeling, we found that many B1-mRNA-expressing cells also exhibited estrogen receptor alpha immunoreactvity in anteroventral periventricular nucleus, medial preoptic nucleus, and arcuate nucleus. Taken together, these results reveal that estrogen may directly modulate expression of B1 mRNA in the hypothalamus and support the idea that transforming growth factors beta play an important role in the hypothalamic control of gonadotropin-releasing hormone function.

Gender differences in proenkephalin gene expression response to ∆9-tetrahydrocannabinol in the hypothalamus of the rat

Chronic exposure to delta9-tetrahydrocannabinol (delta9-THC) produces an activation of preproenkephalin (PENK) gene expression in the rat hypothalamus. The levels of circulating gonadal steroids concurrently modulate this neuropeptide in male and female rats. However, whether gonadal steroids regulate delta9-THC effects on PENK gene expression in the hypothalamus of male and female rats remains unknown. To test this hypothesis, experiments were carried out on intact, 2-week-gonadectomized, 1-week-gonadectomized, 1-week-dihydrotestosterone (DHT) replaced male rats, and 2-week-gonadectomized, 1-week-gonadectomized, 1-week-oestradiol replaced female rats. One week after hormonal replacement, animals were treated with vehicle or delta9-THC (5 mg/kg/day, i.p. 7 days). In males, delta9-THC administration to intact animals induced PENK mRNA in the paraventricular nucleus (PVN) and ventromedial nucleus (VMN) of the hypothalamus. Orchidectomy did not affect basal PENK mRNA levels in the PVN, but reduced PENK mRNA levels in the VMN. However, delta9-THC treatment induced PENK gene expression to the same extent in both hypothalamic nuclei of intact, castrated and DHT-replaced males. In females, ovariectomy decreased PENK gene expression in PVN and VMN. delta9-THC administration increased PENK gene expression in castrated females, but had no effect in the oestradiol-replaced group. Taken together, these results suggest gender differences in the response of chronic exposure to cannabinoids on PENK gene expression in the hypothalamus. Furthermore, it appears that alterations in opioid gene expression induced by cannabinoids in female rats depend upon the presence or absence of circulating oestradiol.

Chronic ingestion of ethanol or glucose solutions affects hypothalamic and limbic TRH metabolism in dams and their pups

The effect of chronic ethanol consumption during pregnancy and lactation on thyrotropin releasing hormone (TRH) metabolism was investigated in the hypothalamus and limbic areas of female rats and their weaned pups. Pregnant female rats received ethanol or isocaloric glucose solution during pregnancy either alone, or also during the 3 weeks of lactation. Thyrotropin (TSH) and corticosterone levels were measured in serum; TRH and TRH-gly concentrations were determined in hypothalamus, hippocampus, n.accumbens, frontal cortex and amygdala of dams and pups at 21 days after parturition. Ethanol or glucose consumption during pregnancy and lactation produced a decrease in TSH levels compared with control animals fed at libitum; water replacement during lactation normalized TSH levels only in glucose-fed dams. Pups from ethanol or pair-fed dams showed low weight and increased TSH levels compared with normal rats. Variations in TRH metabolism were detected in limbic areas. Chronic ethanol caused a decrease in the levels of TRH in the hippocampus and frontal cortex of dams. In contrast, glucose chronic ingestion increased TRH content specifically in n.accumbens and amygdala of dams. Most of the variations in TRH content of limbic areas of pups were not specific for glucose or ethanol treatment and correlated with the deleterious effect of the mother’s thyroid condition, although some differences were observed depending on pup’s gender. These results support the involvement of TRHergic neurons in the limbic system of the female rat exposed to alcohol or glucose during pregnancy and lactation.

Sexually dimorphic expression of prepro-orexin mRNA in the rat hypothalamus

The neuropeptides orexin A and B are expressed in the lateral hypothalamic area and are involved in the regulation of energy homeostasis and arousal. Recent results showed gender differences in the expression of orexin receptor subtypes in rats. In the present study, we analyzed the mRNA expression of prepro-orexin (PPO) in the hypothalamus of male and female rats using quantitative real-time PCR. We found significantly higher levels of PPO mRNA in the hypothalamus of female rats compared to male rats. Our study indicates a sex-dependent regulation of hypothalamic PPO expression and suggests gender-specific functions of orexins.