Estrogen-treated Rats Research Articles

Involvement of β-adrenergic receptor of nucleus tractus solitarius in changing of baroreflex sensitivity by estrogen in female rats.

Background:Arterial baroreflex (ABR) is an important factor in preventing of blood pressure fluctuations that determined by baroreflex sensitivity (BRS). Estrogen is an ovarian hormone that has influence on ABR. The mechanism of this effect of estrogen unknown and may be mediated by β-adrenergic receptor of nucleus tractus solitarius (NTS), an important area in regulation of baroreflex. Therefore, in this study changing of BRS by estrogen after blockade β-adrenergic receptor of NTS in ovariectomized rats (Ovx) and Ovx treated with estrogen (Est) was examined.Materials and Methods:After ovariectomy, all female rats divided to Ovx and Ovx + Est groups and two series of experiments were performed. In the first experiment, phenylephrine was [intravenously, IV] injected in both the Ovx and Ovx + Est groups, and mean arterial pressure (MAP), heart rate (HR), and BRS were evaluated (n = 8 for each group). In the second experiment, each of Ovx and Ovx + Est groups divided into saline and propranolol (pro) groups, saline and pro stereotaxically were microinjected into NTS, respectively. Further, phenylephrine (IV) was injected in all groups and BRS was evaluated.Results:BRS significantly increased in estrogen-treated groups (Ovx + Est) compared to Ovx groups (P < 0.01). The blockade β-adrenergic receptor of NTS by pro did not significantly changed BRS in both Ovx and Ovx + Est groups.Conclusion:We concluded that there aren’t any intraction between estrogen and β-adrenergic receptor of NTS in BRS.

Neonatal Exposure to Estradiol Valerate Increases Dopamine Content in Nigrostriatal Pathway During Adulthood in the Rat

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter.

Pyrethroid and their metabolite, 3-phenoxybenzoic acid showed similar (anti)estrogenic activity in human and rat estrogen receptor α-mediated reporter gene assays

Pyrethroids are commonly used as pesticides which are suspected as endocrine disruptors in many studies; however, still we do not know their effects on different species. To compare their effects on human estrogen receptor (hERα) and rat estrogen receptor (rERα), we developed a hERα and rERα mediated luciferase reporter assay to investigate the (anti)estrogenic activities of three frequently used pyrethroids (fenvalerate, cypermethrin, permethrin) and their metabolite 3-phenoxybenzoic acid (3-PBA). All three pyrethroids significantly induced expression of the luciferase, while none of them were antagonistic to 1nM E2 mediated induction. Interestingly, 3-PBA, showed antagonist activity by decreasing the effect of 1nM E2 to 55.12% in hERα assay and to 45.12% in rERα assay. Our results firstly demonstrated that pyrethroids and 3-PBA showed similar response in the hERα and rERα mediated reporter gene assay, which indicated that data derived from reporter gene assay or other receptor mediated assay systems with rat ER system might be used to predict to estrogenic or anti-estrogenic effects to human systems.

Fetal growth restriction alters hippocampal 17-beta estradiol and estrogen receptor alpha levels in the newborn male rat

Fetal growth restriction (FGR) is associated with impaired neurodevelopmental outcomes in affected newborns. The pathogenesis of FGR-associated neurodevelopmental impairment implicates abnormal hippocampal function. The steroid hormone estrogen and its receptor, estrogen receptor alpha (ERα), are involved in the normal programming of hippocampal development and structure. However, the impact of FGR on hippocampal estrogen and hippocampal ERα is not well characterized. We hypothesized that FGR will reduce hippocampal and serum levels of 17-beta estradiol and its receptor, ERα, in the newborn rat hippocampus. We further hypothesize that FGR will reduce hippocampal ERα levels in a region-specific manner. To test our hypotheses, we used the well characterized rat model of FGR induced by uteroplacental-insufficiency in the pregnant Sprague-Dawley rat. Hippocampi and serum were obtained from FGR and control day 0 rat pups and examined for hippocampal 17-beta estradiol, serum 17-beta estradiol, and ERα mRNA and protein levels. Immunohistochemistry was performed to examine region-specific ERα staining. FGR decreased hippocampal 17-beta estradiol levels in the hippocampi of male newborn rats but not females. Serum 17-beta estradiol levels were not affected by FGR in either gender. FGR decreased hippocampal ERα mRNA levels in males but not females. Hippocampal ERα protein levels by Western blotting were not affected by FGR. However, FGR decreased apparent ERα staining in the cornu ammonis (CA)1, CA3, and dentate gyrus regions in the hippocampi of male newborn rats but not females. We conclude that FGR affects the programming of hippocampal estrogen and hippocampal ERα levels in the newborn rat in a gender-specific manner.

Serotonin is possibly involved in the anorexigenic and antidepressant effects of estrogen in ovariectomized rats

Estrogen attenuates food intake and enhances c‐Fos expression in the suprachiasmatic nucleus (SCN) specifically during the light phase in ovariectomized rats, and also has the antidepressant effect. Serotonin (5HT) neurons play an important role in the food intake, the pathogenesis of depression, and the formation of circadian rhythm. To test the hypothesis that 5HT is involved in the anorexigenic and antidpressant effects of estrogen, we examined the effect of selective serotonin reuptake inhibitor (SSRI) administration on food intake, depression like behavior and c‐Fos expression in the SCN in ovariectomized rats. Rats were ovariectomized and implanted either with an estradiol (E2 group) or a cholesterol (Veh group) containing silicon tubing. SSRI was injected at the beginning of the light and dark phases for 10 days. SSRI attenuated the food intake specifically during the light phase in the both groups, and reduced depression‐like behaviors in the Veh group. The number of c‐Fos like immunoreactive cells in the SCN during light phase was larger in the E2 than the Veh group, and SSRI increased the c‐Fos expression in the ventrolateral SCN only in the Veh group. These suggest that 5HT is possibly involved in the estrogen‐induced anorexigenic and antidepressant effects by changing the response to photic stimulation.

Raloxifene supports early fracture healing more than estrogen in ovariectomized rats

Summary Objectives: Most people suffering from osteoporosis are undiagnosed: the first osteopenic fracture strikes an untreated organism. Therefore implant fixation often fails and bone healing is disturbed. In this basic research project, we explore possibilities to improve the quality of the osteopenic bone immediately after a fracture to avoid these complications. Methods: Thirty-six female rats, which developed osteopenia within ten weeks duration after ovariectomy (OVX), underwent a standardized metaphyseal osteotomy with a bridging T-plate-fixation. After that rats were divided into three groups, which received soyfree food supplemented with raloxifene (R: 2.02 mg/d) or estradiol-17β-benzoate (E: 0.09 mg/d), orally, or soyfree food (SF) only. During fracture healing the rats were subcutaneously injected with fluorescent agents to help label and visualize the process of bone formation. Bones were analyzed using a three-point bending test, histological sections and microradiographs. Results: Raloxifene and estradiol have exerted anabolic effects on the trabecular bone. Both substances induced fracture healing mainly via endosteal callus formation (R: 2.08 ± 0.66 mm2, E: 2.02 ± 0.75 mm2 vs. SF: 1.78 ± 0.74 mm2). Due to early bridging and advanced fracture healing, less bone occurred in the later stages after application of test substances. The biomechanical features of the callus formations determined by the Yield load of R- (100.3 ± 28.4 N) were at the level of E-treated bone (93.8 ± 29.7 N) being higher in both comparing to the osteopenic bones (SF: 76.4 ± 18.8 N). Conclusions: Raloxifene and estrogen had supporting effects in the therapy of fractures of osteopenic bone. They improved not only the bone, but also the callus structure. The raloxifene- and estradiol-treatment enhanced the mechanical properties of the osteopenic bone, which probably lead to (micro) fracture risk reduction. Taking into account all the results there is an advantage for raloxifene; additionally its negative side effects detected in human settings, with respect to e. g. breast cancer propagation, are less than that of estrogens.

Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood.Objective. The aim was to investigate this question.Material and methods. A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17β-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed.Results. Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 β-estradiol. In males, 17 β-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology.Conclusions. Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function.

The effects of Aloe Vera sap on progesterone, estrogen and gonadotropin in female rats

The effects of Aloe Vera sap on progesterone, estrogen and gonadotropin in female rats

Are the neuroprotective effects of estradiol and physical exercise comparable during ageing in female rats?

Ageing of the brain is accompanied by variable degrees of cognitive decline. Estrogens have profound effects on brain ageing by exerting neurotrophic and neuroprotective types of action. Furthermore, exercise has also been claimed to play a role in the non-pharmacological prevention of psycho-neuronal decline with ageing. In the present study the question was asked whether chronic physical exercise might substitute the action of estrogens in aged rats. We compared the effects of 17β-estradiol (E2) treatment and long-term moderate physical exercise in ageing (15 months, early stage of ageing) and old (27 months) female rats, on cognitive functions and the relevant intracellular molecular signaling pathways in the hippocampus. Results showed that both treatments improved attention and memory functions of the 15 months old rats. Like E2, physical training enhanced the level of brain derived nerve growth factor and the activation of PKA/Akt/CREB and MAPK/CREB pathways. The treatments also enhanced the levels of synaptic molecules synaptophysin and synapsin I, which could explain the improved cognitive functions. In the 27 months old rats the behavioral and molecular effects of E2 were indistinguishable from those found in the 15 months old animals but the effects of physical exercise in most of the measures proved to be practically ineffective. It is concluded that the effectiveness of regular and moderate intensity physical exercise is age-dependent while the action of E2 treatment is comparable between the ageing and old female rats on maintaining cognition and its underlying molecular mechanisms.

Structural and functional changes in the alveolar bone osteoclasts of estrogen‐treated rats

This study investigated structural and functional features of apoptotic alveolar bone osteoclasts in estrogen-treated rats. For this purpose, 15 female rats 22 days old were divided into three groups: Estrogen (EG), Sham (SG) and Control (CG). The rats of EG received daily intramuscular injection of estrogen for 7 days. The SG received only the oil vehicle. Maxillary fragments containing alveolar bone were removed and processed for light and transmission electron microscopy. Area (OcA) and number of nuclei (OcN) and bone resorption surface per TRAP-positive osteoclasts (BS/OC) were obtained. Vimentin, caspase-3 and MMP-9 immunoreactions, TUNEL/TRAP and MMP-9/TUNEL combined reactions were performed. In EG, the OcA, OcN and BS/Oc were reduced. Moreover, osteoclasts showed cytoplasm immunolabelled by caspase-3 and a different pattern of vimentin expression in comparison with CG and SG. MMP-9 expression was not affected by estrogen and the TUNEL-positive osteoclasts were MMP-9-immunolabelled. In EG, ultrastructural images showed that apoptotic osteoclasts did not exhibit ruffled borders or clear zones and were shedding mononucleated portions. TRAP-positive structures containing irregular and dense chromatin were partially surrounded by fibroblast-like cells. In conclusion, the reduction in the BS/Oc may be due to reduction in OcA and OcN; these effects seem to be related to vimentin disarrangement rather than to an interference of estrogen with osteoclast MMP-9 expression. Osteoclast apoptosis involves caspase-3 activity and vimentin degradation; these cells release portions containing one apoptotic nucleus and, subsequently, undergo fragmentation, giving rise to apoptotic bodies.

P.1.c.015 The role of estrogen and testosterone in female rats in behavioural models of relevance to schizophrenia

P.1.c.015 The role of estrogen and testosterone in female rats in behavioural models of relevance to schizophrenia

Effects of Estrogen and Keishibukuryogan on Hot Flash-like Symptoms Induced by Yohimbine in Ovariectomized Rats

Hot flash (HF) is the most common phenomenon in climacteric symptoms which often develop concomitantly with a decrease in estrogen in postmenopausal women. The onset mechanism of the hot flash is complicated and remains unclear. To date, some animal models of postmenopausal HF have been devised, but they are not fully available because of the difficulty in producing them. It is thought that hyperactivity of the central α-adrenergic system with a decrease in estrogen participates in the onset of postmenopausal HF. Therefore, in the present study, we examined whether a HF model could be easily produced by administering yohimbine (YOH), a presynaptic α₂-adrenoceptor antagonist which promotes norepinephrine release, to female rats. HF-like symptoms such as a rise in tail skin temperature and a fall in rectal temperature were shown in the rats who received YOH (3 mg/kg) subcutaneously seven days after the ovariectomy (OVX). Such symptoms following YOH administration were observed in sham rats as well, but were much more clearly noted in OVX rats. We next examined the effects of various drugs, which are clinically effective against postmenopausal HF, on HF-like symptoms in YOH-treated OVX rats: clonidine, a presynaptic α₂-adrenoceptor agonist which inhibits norepinephrine release; β-estradiol as an estrogen; and Keishibukuryogan, a Kampo medicine. These drugs inhibited HF-like symptoms in YOH-treated OVX rats. These results suggest that the activity of the α-adrenergic system is enhanced with a decrease in estrogen in OVX rats whereby YOH causes HF-like symptoms more conspicuously than in sham rats. Therefore, it is thought that YOH-treated OVX rats will be a novel and simple model of postmenopausal HF.

The role of estrogen and testosterone in female rats in behavioral models of relevance to schizophrenia

The sex steroid hormone, estrogen, may play a protective role in schizophrenia. We previously found that estrogen treatment inhibited serotonin-1A (5-HT(1A)) and dopamine D(2) receptor-mediated disruptions of prepulse inhibition (PPI), a measure of sensorimotor gating which is deficient in schizophrenia. The present study aimed to further explore the role of sex steroid hormones in schizophrenia. Part 1 of this study examined whether estrogen could inhibit PPI disruption induced by the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801. Part 2 investigated whether the functionally protective effect of estrogen occurs in another animal model of schizophrenia, amphetamine-induced locomotor hyperactivity. Part 3 compared our previous PPI findings in estrogen-treated rats, to treatment with testosterone. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants filled with either a low (E20) or high dose (E100) of estradiol, or a low (T5) or high dose (T20) of testosterone, for at least 2 weeks before behavioral testing. The disruption of PPI caused by MK-801 (0.1 mg/kg) was significantly reduced by treatment with estradiol (E20 and E100). However, estradiol treatment did not alter amphetamine-induced (0.25 and 0.5 mg/kg) locomotor hyperactivity, in terms of distance traveled, ambulation, or vertical counts. In contrast to estrogen, testosterone treatment did not affect disruption of PPI after administration of 8-OH-DPAT (0.5 mg/kg) or apomorphine (0.3 mg/kg). Testosterone treatment significantly enhanced the MK-801-induced (0.1 mg/kg) PPI disruption. Estrogen is functionally protective against 5-HT(1A)-, dopamine D(2)-, and NMDA receptor-induced PPI disruptions, while testosterone treatment enhances NMDA receptor-mediated PPI disruptions.

Skeletal effects of bazedoxifene paired with conjugated estrogens in ovariectomized rats

A novel approach to menopausal therapy is the tissue selective estrogen complex (TSEC) that partners bazedoxifene (BZA) with conjugated estrogens (CE). We examined the effects of daily treatment with BZA 0.3mg/kg, CE 2.5mg/kg, or combined BZA/CE (BZA 0.1, 0.3, or 1.0mg/kg with CE 2.5mg/kg) over 12months on bone mass, bone architecture and strength, and biochemical markers of bone turnover in ovariectomized (OVX) female Sprague-Dawley rats vs OVX control rats. Total cholesterol and uterine weights were also evaluated. All BZA/CE dose combinations prevented ovariectomy-induced increases in bone turnover and significantly increased bone mineral density (BMD) at the lumbar spine, proximal femur, and tibia compared with OVX controls. All BZA/CE doses evaluated also prevented many of the ovariectomy-induced changes of the static and dynamic parameters of the cortical compartment of the tibia and the cancellous compartment of the L1 and L2 vertebrae. All BZA/CE doses increased biomechanical strength at the lumbar spine (L4) compared with OVX animals. The co-administration of BZA 0.3 and 1.0mg/kg/day with CE 2.5mg/kg/day showed a dose-dependent reduction in uterine wet weight compared with administration of CE alone. All BZA/CE doses significantly lowered total cholesterol levels compared with OVX controls. In conclusion, 12months of treatment with BZA/CE in OVX rats effectively maintained BMD, bone microstructure, and bone quality; and the pairing of BZA with CE prevented CE-induced uterine stimulation.

Thyroid gland dysfunction modulates ovarian response to estrogen and androgen receptors in albino rats

The Egyptian Journal of Histology 2011, 34:182–190 17 (1254 -2011) Background Hypothyroidism and hyperthyroidism are more common in women than in men, and it was reported that thyroid hormones play an essential role in ovarian physiology. Aim This study aimed to simulate the clinical conditions of hypothyroidism and hyperthyroidism in adult female albino rats, and to detect the possible changes in ovarian estrogen and androgen hormone receptors associated with such clinical conditions. Materials and methods This study used 36 adult female albino rats. Rats were divided into three groups, with 12 rats each. Rats of the control group received 0.5 ml saline (0.9%) solution once daily. Six rats received the saline orally using a tube, and the other half received it by intraperitoneal injection for 4 weeks. The rats of the hypothyroid group received daily orally a dose of 18.75 mg/kg propylthiouracil dissolved in saline solution for 4 weeks, and the rats of the hyperthyroid group received a daily intraperitoneal dose of 40 mg/kg L-thyroxine dissolved in saline solution for 4 weeks. Vaginal smears were performed at the end of the experiment; only 22 rats coincided the diestrus phase of the cycle, sacrificed and sections were subjected to hematoxylin and eosin and immunohistochemical staining for estrogen and androgen receptors. Results In the hypothyroid group, few corpora lutea, atretic follicles, and dilated congested blood vessels were clearly seen. In the hyperthyroid group, the ovarian sections showed numerous corpora lutea; atretic follicles and markedly dilated congested blood vessels were also noted. A negative correlation was documented between estrogen receptor and androgen receptor immunoreactivity in the hypothyroid and hyperthyroid groups. Conclusion This study suggested that thyroid hormones are important to maintain a normal estrous cycle and hence in the regulation of ovarian hormones. The mechanisms by which thyroid hormones influence ovarian function remain to be elucidated. However, it might be through their effect on the aromatase enzyme, which is the key regulator in ovarian hormones production reflected on the level of steroid hormones receptor expression.

Genetically Induced Estrogen Receptor α mRNA (Esr1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice

Previously, we reported that estrogen receptor α mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and maldeveloped penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < .05) lower as compared with controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, genetically induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except for limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles.

Testosterone and oestradiol in concert protect seminiferous tubule maturation against inhibition by GnRH-antagonist

Oestradiol enhances follicle stimulating hormone (FSH) action on seminiferous tubule maturation, but the relative involvement of oestradiol and testosterone remains unclear. This study compares the influences of oestrogen and androgen in FSH and testosterone-deficient rats. Animals were injected daily GnRH-antagonist alone (Ant) or combined with 17β-oestradiol benzoate (EB), or testosterone propionate (TP), or both from post-natal day (pnd) 5 to 15. Hormone levels, tubule growth, cell numbers, germ cell apoptosis and proliferation, and Sertoli cell maturation were evaluated on pnd 16. Ant decreased serum FSH and testosterone levels to ∼60% and ∼50% of control values, respectively, and decreased tubule growth, Sertoli cell number and maturation. Germ cell number declined by apoptosis. Co-administration of EB stimulated spermatogonia proliferation and maintained FSH levels (86% of control). Tubule growth, Sertoli cell number and spermatocyte apoptosis remained normal after TP co-administration, but Sertoli cell maturation, germ cell number and spermatogonia survival were reduced. Co-administration of EB with TP prevented all inhibitions. In conclusion, administration of oestradiol with testosterone, but neither one alone, protected seminiferous tubule maturation against inhibition caused by Ant-induced disruption. Oestrogen was involved in stimulating germ cell proliferation and the maintenance of Sertoli cell maturation, whereas androgen affected seminiferous tubule growth and spermatocyte survival.

The spontaneous firing rates of dopamine-inhibited dorsomedial arcuate neurons exhibit a diurnal rhythm in brain slices obtained from ovariectomized plus estrogen-treated rats

The activity of tuberoinfundibular dopaminergic (TIDA) neurons exhibits a diurnal rhythm in female rats, as determined by neurochemical investigation. Whether the spontaneous firing rates of presumed TIDA neurons in the dorsomedial arcuate nucleus (dmARN) also exhibit a diurnal pattern has yet to be ascertained. Single-unit activities of 131 dmARN neurons were recorded in brain slices prepared from 83 ovariectomized plus estrogen-primed rats, and grouped according to their responses to dopamine and the time at which they were observed. In dopamine-inhibited dmARN neurons, significantly lower firing rates were observed in the afternoon compared to those recorded in the morning (2.51 ± 0.27 Hz, n = 15, from 1130 to 1330 h vs. 1.08 ± 0.07 Hz, n = 47, from 1430 to 1630 h). No such change was observed in dopamine-excited or nonresponsive dmARN neurons (1.83 ± 0.32 Hz, n = 9 vs. 1.46 ± 0.17 Hz, n = 21). Four dmARN neurons were continuously recorded from 1130 to 1600 h or even longer until 2000 h. The averaged firing rates decreased significantly between 1300 and 1600 h, two neurons were also inhibited by dopamine and a selective D 2 receptor agonist, PHNO, in both normal and low Ca 2+, high Mg 2+ perfusion mediums. This study revealed the existence of diurnal changes in the firing rates of dopamine-inhibited dmARN neurons. These results are strongly correlated with the rhythmic changes observed in TIDA neuronal activity determined through neurochemical methods.

The Role of the Bed Nucleus of the Stria Terminalis in Stress-Induced Inhibition of Pulsatile Luteinising Hormone Secretion in the Female Rat

The bed nucleus of the stria terminalis (BNST) occupies a central position in the neural circuitry regulating the hypothalamic-pituitary-adrenocortical axis response to stress. The potential role of the BNST in stress-induced suppression of the gondotrophin-releasing hormone (GnRH) pulse generator, the central regulator of the reproductive system, was assessed by examining the effects of micro-infusion of corticotrophin-releasing factor (CRF) or its antagonist into the BNST on pulsatile luteinising hormone (LH) secretion or stress-induced inhibition of LH pulses, respectively. Ovariectomised oestrogen-treated rats were implanted chronically with bilateral cannulae in the dorsolateral BNST and i.v. catheters. CRF (25, 50 or 100 pmol in 200 nl of artificial cerebrospinal fluid) administered bilaterally into the BNST resulted in a dose-dependent decrease in LH pulse frequency, and induced Fos expression in glutamic acid decarboxylase immunostained neurones in the medial preoptic area. These results suggest that the activation of hypothalamic GABAergic neurones in response to intra-BNST administration of CRF may be involved in the suppression of LH pulses. Furthermore, administration of CRF antagonist (280 pmol astressin-B, three times at 20-min intervals) into the BNST effectively blocked the suppression of pulsatile LH secretion in response to restraint (1 h) but not hypoglycaemic (0.25 U insulin/kg, i.v.) stress. These data suggest that CRF innervation of the dorsolateral BNST plays a key, but differential, role in stress-induced suppression of the GnRH pulse generator.

Genetically-Induced Estrogen Receptor Alpha (ESR1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice.

Previously, we reported that ESR1 overexpression resulting from neonatal exposure to estrogens in rats and wild-type mice was associated with infertility and mal-developed penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing ESR1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls, as a result of ESR1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < 0.05) lower as compared to controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, this study concludes that the genetically-induced ESR1 overexpression in male mice does not adversely affect fertility, penis, testis or epididymis, but significantly reduces weights of the seminal vesicles and BS/LA muscles. (poster)