bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anxiolytic Effect of Progesterone is Mediated by the Neurosteroid Allopregnanolone at Brain GABAA Receptors
Authors: Bitran Daniel , Shiekh Michael , McLeod Michael 
Published: September 2006

AbstractPrevious studies from this laboratory have shown that progesterone (PROG) treatment in ovariectomized rats produces an anti‐anxiety response similar to that observed after the administration of prototypical anxiolytic benzodiazepine (BDZ) compounds. The PROG‐induced anxiolytic response was highly correlated with an increased level of 3α‐hydroxy‐5α‐pregnan‐20‐one (allopregnanolone) in the blood and brain, and was also associated with a facilitation of GABA‐stimulated chloride ion (Cl−) influx in cortical synaptoneurosomes. This correlative evidence suggested that the anxiolytic effect of PROG was a result of its in vivo reduction to the neuroactive steroid, allopregnanolone. In this report, a series of studies was conducted to determine the mechanism(s) by which PROG alters behavior in animal models of anxiety. In the first experiment, ovariectomized rats were injected with PROG (1 mg/0.2 ml, SC) 4 h prior to a test in the elevated plus‐maze. Some animals also received an injection of picrotoxin (0.75 mg/kg, IP), a GABAA receptor‐gated Cl− channel antagonist, whereas other animals were pretreated with RU 38486 (5 mg/0.2 ml, SC), a progestin receptor antagonist. PROG elicited anxiolytic behavior in the plus‐maze, an effect that was blocked by picrotoxin administration. Pretreatment with RU 38486 was not effective in altering PROG‐induced anxiolytic behavior in the plus‐maze. In a second experiment, the effect of PROG on behavior in the plus‐maze was determined in the presence of N,N‐diethyl‐4‐methyl‐3‐oxo‐4‐aza‐5α‐androstane‐17β‐carboxamide (4‐MA; 10 mg/0.2 ml, SC), a 5α‐reductase inhibitor. The enzyme inhibitor was potent in preventing the anxiolytic effect observed in the plus‐maze after PROG administration. In the defensive burying paradigm, PROG treatment also produced anxiolysis by reducing the duration of burying behavior, and this effect was prevented by 4‐MA pretreatment, but not by RU 38486 administration. After the completion of the behavioral assays, analysis of blood allopregnanolone levels revealed a marked increase in PROG‐treated females. The PROG‐induced elevation in circulating allopregnanolone was blocked by pretreatment with 4‐MA. In cortical synaptoneurosomes, the sensitivity (inverse of the EC50) and the maximal response (Emax) in GABA‐stimulated 36Cl− uptake were increased in PROG‐treated females. The potentiation of PROG on both of these neurochemical measures was not observed in animals pretreated with 4‐MA. Together, these studies provide evidence that the anxiolytic effect of PROG is not associated with an intracellular steroid receptor that initiates genomic‐mediated responses. The evidence is consistent with a nongenomic mechanism whereby PROG is metabolized to allopregnanolone, a neuroactive steroid that potentiates GABAA receptor‐mediated responses.
5β‐Reductase and other Androgen‐Metabolizing Enzymes in Primary Cultures of Developing Zebra Finch Telencephalon
Authors: Schlinger Barney A. , Amur‐Umarjee Shashi , Campagnoni Anthony T. , Arnold Arthur P. 
Published: September 2006

AbstractEnzymes in the avian brain irreversibly catalyze the conversion of androgens into either active metabolites (aromatase and 5α‐reductase) or inactive metabolites (5β‐reductase). 5β‐reductase is thought to influence the formation of active metabolites by reducing the concentration of androgenic substrate available for these reactions. However, because these enzymes have different regional, cellular and subcellular distributions in brain, the traditional method to measure enzyme activity in brain homogenates may be inaccurate because of artificial mixing of enzymes. Recently, we have prepared primary cell cultures from the telencephalons of developing zebra finches. Cell cultures offer the advantage that enzyme activity can be measured in live cells in which the relative distribution of enzymes may more closely reflect that found in vivo. We have previously reported that aromatase is expressed at high levels in these cultures, and that it is active in both neurons and in glia. Here we report on the activities of 5α‐ and 5β‐reductase in these cell cultures. Along with aromatase, 5β‐reductase was expressed at high levels in these mixed cell cultures, including cultures highly enriched in glia. This suggests that 5β‐reductase is present in non‐neuronal cells in brain, possibly co‐localized with aromatase. However, despite the presence of 5β‐reductase, aromatase was detected reliably in vitro even when the concentration of substrate was low. Thus, 5β‐reductase does not prevent the synthesis of estrogen in the telencephalon of developing zebra finches. By contrast, 5α‐reductase activity was very low or absent in these cultures. Thus, cells expressing 5α‐reductase may be poorly represented in these cultures. Alternatively, 5α‐reductase and aromatase together may interfere with the synthesis of 5α‐reduced androgens in the zebra finch telencephalon.
Estradiol Induces Vasoactive Intestinal Peptide and Prolactin Gene Expression in the Rat Anterior Pituitary Independently of Plasma Prolactin Levels
Authors: Montagne Marie‐Noëlle , Dussaillant Monique , Chew Li‐Jin , Berod Anne , Lamberts Steven J. , Cartert David A. , Rostene William 
Published: September 2006

AbstractIt is well established that estrogens are potent stimulators of prolactin (PRL) secretion. It has also been demonstrated that estradiol (E2) can increase the expression and the anterior pituitary levels of the vasoactive intestinal peptide (VIP), a peptide which also acts as a potent PRL‐releasing factor. It thus remained unknown whether the effects on pituitary VIP were due to E2 itself or to E2–induced hyperprolactinemia (HPRL). In order to test this hypothesis, various plasma PRL levels were induced in rats either with ectopic pituitary grafts, PRL secreting tumours or E2 implants, and VIP mRNA expression in the anterior pituitary was measured by in situ hybridization and Northern blot analyses. Whereas decreases in VIP mRNA can be observed in pituitaries of rats with pure HPRL, a 6‐fold increase in VIP mRNA can be seen in E2‐treated rats. E2 increased both 1.0 and 1.7 Kb VIP mRNA species. The presence of the graft in E2‐treated rats significantly reduced the increase in VIP mRNA observed following E2. The direct stimulation by E2 of VIP mRNA expression was further demonstrated by the fact that statistical analysis of the data indicated that both E2 and graft were acting independently of each other, and that a new selective antiestrogen, RU 58668, almost totally blocked the effect of E2. Moreover, under similar experimental conditions, pituitary PRL mRNA levels were reduced in the graft group and a marked up‐regulation was observed similarly in both E2 and in E2 rats bearing ectopic grafts. We observed furthermore that not only levels of the mature 1.0 Kb PRL mRNA but also the 1.7 and 3.8 KbPRL precursor RNAs were increased. Such changes were associated with modifications in PRLmRNA size due to an increase in 3′polyA tail lenghts. The present data demonstrate that E2 directly affects VIP mRNA and PRL mRNA expression in the pituitary and support the hypothesis that VIP may play a role in the hypersecretion of PRL associated with the formation of E2‐induced prolactinomas.
Estrogen‐Sensitive Oxytocin Binding Sites are Differently Regulated by Progesterone in the Telencephalon and the Hypothalamus of the Rat
Authors: Krémarik P. , Freund‐Mercier M. J. , Stoeckel M. E. 
Published: September 2006

AbstractThe localization at the cellular level and the regulation by progesterone of the estrogen‐sensitive oxytocin binding sites was studied in the rat telencephalon and the hypothalamus by using quantitative film‐autoradiography and histoautoradiography. Male rats (castrated or not) and ovariectomized females (estradiol supplemented or not) were used to characterize these sites and to precise their localization. They were detected in the striatal cell bridges, the olfactory tubercle, the principal nucleus of the bed nucleus of the stria terminalis and the medial nucleus of the amygdala of the telencephalon and in the medial preoptic, the ventromedial and the ventral premammillary nuclei of the hypothalamus. Estrogen administration in addition induced expression of oxytocin binding sites in the major island of Calleja, the anterior hypothalamic area and the terete nucleus. The density of the estrogen‐sensitive oxytocin binding sites varied during the estrous cycle, but differently in the telencephalon and the hypothalamus. in the telencephalon it peaked at proestrus 9 h and was already decreased at proestrus 21 h, whereas in the hypothalamus it was similarly high at proestrus 9h and proestrus 21 h, suggesting the intervention of progesterone in the regulation of the hypothalamic estrogen‐sensitive oxytocin binding sites.
Localization in the Nervous System of Drosophila Melanogaster of a C‐Terminus Anti‐Peptide Antibody to a Cloned Drosophila Muscarinic Acetylcholine Receptor
Authors: Harrison J. Barrie , Chen Hong Hong , Blake Allan D. , Huskisson Neville S. , Barker Patrick , Sattelle David B. 
Published: September 2006

AbstractLocalization in the nervous system of Drosophila melanogaster of a cloned Drosophila muscarinic acetylcholine receptor (mAChR) was investigated using a polyclonal antiserum raised against a peptide corresponding to the predicted receptor carboxyl terminal domain. Immunocytochemical studies on fly sections indicated that the product of the Dm1 mAChR gene was localized in the antennal lobes and in other regions of the brain and thoracic nervous system. Intense staining in the glomeruli of the antennal lobes, the region of the nervous system containing terminals of antennal olfactory sensory neurones and mechanosensory neurones, indicates possible roles for this mAChR gene product in the processing of olfactory and mechanosensory signals in the fly. The staining of a discrete group of neurosecretory cells in the pars intercerebralis of the brain indicates a possible new role for this mAChR in the regulation of neurosecretion. Very little staining is detected in the thoracic nervous system.
Three Dimensional Culture of Pineal Cell Aggregates: A Model of Cell‐Cell Co‐operation
Authors: Khan Naim A. , Shacoori Valiollah , Havouis Réné , Querné Dominique , Moulinoux Jacques‐Ph. , Rault Bernard 
Published: September 2006

AbstractThree dimensional (3‐D) cultures of pineal cell aggregates were obtained by constant gyratory shaking the heterogenous cell populations, obtained from the rat pineals, in the DMEM (Dulbecco's modified Eagle's medium). Within 4 days, the pineal cells became organized into a tissue like configuration appearing as a compact ball, evidenced by the scanning electron microscopy. The 3‐D aggregates seemed to be mainly composed of pinealocytes (round‐oval cells), glial (elongated cells) and other unknown cells. The heterogenous cells were separated by intercellular spaces. The ultrastructural characteristics revealed by transmission electron microscopy exhibited the presence of granular lysosomes, typical of pinealocytes actively involved in the secretion. These pineal cell aggregates secreted melatonin and other indole amines i.e. 5‐methoxytryptamine (5‐MT), indole acetic acid (IAA), 5‐methoxy‐3‐indole acetic acid (5‐MIAA), tryptophol (TOL) and 5‐methoxytryptophol (5‐MTL) in the culture medium, indicating the functional aspect of pinealocytes. The 3‐D aggregates cultures had advantages over the pineal monolayer cultures as, after 4 days of culture, the amounts of indole amines secreted by 3‐D aggregates were higher than those secreted by monolayer cultures. Besides, the 3‐D aggregates remained functional till 24 days in the gyratory culture conditions. In the continuous perifusion system, the 3‐D aggregates secreted melatonin while challanged with isoproterenol. This 3‐D model of pineal cell aggregates might be useful, in future, to perform other kinetic studies of the release of indole amines in perifusion experiments as this system allows the maintenance of pineal cells for a long period of time.
The Emerging Concept of Relaxn as a Centrally Actng Peptide Hormone with Hemodynamic Actions
Authors: Geddes Brad J. , Summerlee Alastair J. S. 
Published: September 2006

AbstractThe novel finding that relaxin has an action on the brain was first published in 1984. Since then, it has been shown that exogenous relaxin affects the release of a number of hypothalamo‐pituitary hormones and has a robust pressor action. In this paper, we review the accumulating evidence that relaxin affects the release of oxytocin and vasopressin by an action at the level of the brain. The potential mechanisms of this central action are discussed and the evidence presented for the interaction between relaxin and the forebrain angiotensin‐ll system. Furthermore, we articulate the possible physiological influences of relaxin on the changes in cardiovascular function that occur during pregnancy.
Central Oxytocin Mediates Stress‐Induced Tachycardia
Authors: Morris Mariana , Callahan Michael F. , Li Ping , Lucion Aldo B. 
Published: September 2006

AbstractTo address the role of oxytocin in the control of cardiovascular reactivity, we examined the effect of central injection of oxytocin, vasopressin and mixed base antisense oligodeoxynucleotides on stress‐induced cardiovascular and endocrine changes. Antisense oligomers were injected into the paraventricular nucleus (PVN), 4 h prior to the stress test. The oxytocin antisense abolished the tachycardia produced by 5 min of shaker stress. The blood pressure and plasma oxytocin responses were not different between the groups. PVN levels of OT were reduced in the oxytocin antisense‐treated group while brain stem levels were increased. These results demonstrate the importance of a specific peptide system, the PVN/oxytocin axis, in stress‐induced tachycardia. Further, the data illustrate the effectiveness of short‐term treatment with antisense oligomers on physiological responses.
Caloric Intake Stimulates Growth Hormone Secretion in Food‐Deprived Rats with Anterolateral Deafferentation of the Medial Basal Hypothalamus or Administered Antiserum to Somatostatin
Authors: Suzuki Nobuchika , Okada Kenmei , Sugihara Hitoshi , Minami Shiro , Wakabayashi Ichiji 
Published: September 2006

AbstractIn rats, food deprivation inhibits episodic growth hormone (GH) secretion. On the basis of previous studies, we hypothesized that during a recovery from prolonged fasting, caloric intake stimulates the release of GH‐releasing factor (GRF) and this process does not depend on the specific macronutrients in the meal, while protein in the meal acts to restore characteristic ultradian rhythmicity of GH secretion. To test this hypothesis, the effect of caloric intake on GH secretion was examined in fasted adult male Wistar rats devoid of somatostatin (SS) influence on GH secretion either by anterolateral deafferentation (ALC) of the medial basal hypothalamus (MBH) or administration of anti–SS goat serum (ASS). Rats were provided with an indwelling right atrial cannula and were deprived of food for 72 h. ALC was performed 2 weeks prior to the study. ASS was given i.v. 8 h and 7 h prior to refeeding, respectively. Serial blood specimens were collected every 10 min. fn rats with ALC (ALC rats) or rats given ASS (ASS rats), the blood GH level revealed irregularly occurring small fluctuations, instead of the usual high bursts and low trough level. The baseline GH level and the mean GH level of fasted ALC rats or fasted ASS rats were significantly lower than those of fed ALC rats or fed ASS rats. Feeding the isocaloric mixed meal, the protein meal or the protein‐deficient meal increased the GH pulse frequency, the pulse amplitude, the baseline GH level and the mean GH level in 72–h fasted ALC rats. These changes in GH secretory pattern persisted during the period of observation and were independent of the type of meal ingested. Following feeding the mixed meal, similar changes in the GH secretory pattern demonstrated in 72‐h fasted ALC rats were also observed in 72–h fasted ASS rats, suggesting that the stimulation of GH secretion following caloric intake is not limited to ALC rats. Since the influence of SS on GH secretion has been largely eliminated in ALC or ASS rats, it is highly unlikely that the augmentation of GH secretion following feeding after prolonged food deprivation was the consequence of inhibition of SS secretion. Although GRF measurement was not performed, it is conceivable that the signal of caloric intake is conveyed to the MBH and acts to stimulate GRF release.
Effects of Dehydroepiandrosterone (DHEA) on Pituitary Prolactin and Arcuate Nucleus Neuron Tyrosine Hydroxylase mRNA Levels in the Rat
Authors: De Yebenes Ester Garcia , Hong Min , Pelletier Georges 
Published: September 2006

AbstractIt is well documented that dehydroepiandrosterone (DHEA), an adrenal androgen, is converted into potent androgens and/or estrogens in peripheral tissues. Since sex steroids are involved in the regulation of prolactin (PRL) secretion, we have studied the effect of DHEA administration on PRL mRNA levels in both adult male and female rats. Since tuberoinfundibular dopaminergic (TIDA) neurons are involved in the negative regulation of PRL, we have also evaluated the effects of DHEA on the genetic expression of tyrosine hydroxylase (TH), the limiting enzyme in catecholamine biosynthesis in TIDA neurons. Sham‐operated and castrated animals of both sexes received during 2 days DHEA at the dose of 6 mg/kg/day, starting on the first day after castration. PRL and TH mRNA levels were measured by quantitative in situ hybridization. In the male rat, orchiectomy performed 3 days earlier did not modify PRL mRNA levels. DHEA administration increased the hybridization signal in both sham‐operated and orchiectomized animals. In the female, ovariectomy decreased PRL mRNA levels and, as observed in the male, DHEA treatment induced an increase in the hybridization signal in both control and ovariectomized rats. In TIDA neurons, castration increased TH mRNA levels as evaluated by number of grains over labelled neurons and the number of TH‐labelled cells per section in both male and female animals. In both sham‐operated male rats and orchiectomized animals, DHEA decreased the hybridization signal. In the female, DHEA administration completely prevented the increase in TH mRNA levels due to ovariectomy. In sham‐operated female rats, the treatment had no effect. These data clearly indicate that in both male and female rats DHEA exerts an estrogenic influence on both PRL and TH gene expression. Although these in vivo experiments do not allow to establish whether the stimulation of PRL gene expression is due to an action of the steroid on the pituitary or at the hypothalamic level or alternatively at both sites, it is likely that one of the mechanisms of action of DHEA might be related to a decrease in dopamine release following a depression of TIDA neuron activity.
A Role for the Mineralocorticoid Receptor in a Rapid and Transient Suppression of Hippocampal 5‐HT1A Receptor mRNA by Corticosterone
Authors: Meijer Onno C. , de Kloet E. Ronald 
Published: September 2006

AbstractThe interaction between corticosterone and hippocampal 5‐HT1A receptor mRNA expression was investigated in male rats. Two days after adrenalectomy, 5‐HT1A receptor mRNA was increased in the granule cell layer of the dentate gyrus. Injection of corticosterone led to a significant dose‐dependent and transient suppression of 5‐HT1A receptor mRNA. The effect of a low dose of corticosterone (50 μg/kg) could be blocked by RU 28318, a specific mineralocorticoid receptor antagonist, but not by RU 38486, a glucocorticoid antagonist. The effect of a higher dose of corticosterone (300 μg/kg) could be partially blocked by RU 28318, whereas there was no additional effect of RU 38486. These results point to a stringent regulation of hippocampal 5‐HT1A receptors by corticosterone that is predominantly mediated by the mineralocorticoid receptor.
Distribution of Androgen Receptor‐Like Immunoreactivity in the Brains of Cynomolgus Monkeys
Authors: Michael Richard P. , Clancy Andrew N. , Zumpe Doris 
Published: September 2006

AbstractA polyclonal antibody, PA1, raised in a rabbit against fusion proteins containing fragments of the human prostatic androgen receptor (AR) was used to map the distribution of AR‐like immunoreactivity in the brains of adult male and female cynomolgus monkeys. PA1 AR‐immunoreactive (ARir) labeling occurred in the cell nuclei and, more weakly, in the cytoplasm of brain cells. The PA1 ARir labeling occurred primarily in brain regions previously shown on the basis of gonadal steroid autoradiography to contain androgen receptors. However, the distribution of PA1 ARir staining was substantially more restricted than that of autoradiographic labeling using 3H‐androgens. The pattern of PA1 ARir labeling was closely similar between animals and occurred in the lateral septum, medial preoptic area, bed nucleus of stria terminalis, anterior, cortical, accessory basal and medial amygdala, several hypothalamic nuclei including the supraoptic, anterior, paraventricular, ventromedial and arcuate nuclei, and the premammillary nucleus. No significant sex differences were observed. With the exception of the supraoptic nucleus, reported not to be labeled by autoradiography, earlier autoradiographic findings and the current immunocytochemical results, although not congruent, have noteworthy similarities.
Evidence for Short‐Loop Feedback Effects of ACTH on CRF and Vasopressin Expression in Parvocellular Neurosecretory Neurons
Authors: Sawchenko P. E. , Arias C. 
Published: September 2006

AbstractImmuno‐ and hybridization histochemical methods were used to examine a possible role for adrenocorticotropic hormone (ACTH) in regulating the expression of corticotropin‐releasing peptides in rat hypothalamus. Densitometric assessments of relative levels of mRNAs encoding corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OT) in the parvocellular division of the paraventricular nucleus (PVH) were carried out in intact, adrenalectomized (ADX) and hypophysectomized (HYPOX) animals. Both surgeries resulted in comparable increases in relative levels of CRF and AVP transcripts in the parvocellular PVH; no effects on OT mRNA in this compartment were evident. In a second experiment, ACTH or saline vehicle were administered systemically via osmotic minipump for seven days to rats submitted to both HYPOX and ADX surgeries. Lower replacement doses of ACTH reduced the number of detectable AVP‐immunoreactive (AVP‐ir) cells in the parvocellular PVH to 53% of that seen in vehicle‐treated HYPOX/ADX controls; the number of CRF‐IR cells was not significantly affected. Higher doses of ACTH resulted in counts of AVP‐ and CRF‐IR neurons that were reduced to 32% and 70%, respectively, of control values. Staining patterns for the two peptides in the external lamina of the median eminence generally followed the cell count data. Neither densitometric nor combined immunohistochemical (for CRF‐ir) and hybridization histochemical (for AVP mRNA) assays revealed any marked effect of ACTH on AVP mRNA expression in the parvocellular PVH of HYPOX/ADX rats. The results indicate that ACTH is capable of inhibiting corticotropin‐releasing peptide, but not mRNA, expression in hypophysiotropic neurons. The mechanisms underlying these effects remain to be fully clarified.