bluuebunny/crossref_metadata_2025_split huggingface dataset:
PACAP Stimulation of Gonadotropin‐II Secretion in Goldfish Pituitary Cells: Mechanisms of Action and Interaction with Gonadotropin Releasing Hormone Signalling
Authors: Chang J. P. , Wirachowsky N. R. , Kwong P. , Johnson J. D. 
Published: March 2003

AbstractPituitary adenylate cyclase‐activating polypeptide (PACAP) has recently been shown to be a hypophysiotropic factor in the goldfish. In this study, we examined the mechanisms of PACAP action on goldfish maturational gonadotropin (GTH‐II) release using primary cultures of pituitary cells. The GTH‐II response to mammalian PACAP1−38 (mPACAP) was inhibited by a PACAP receptor antagonist suggesting a receptor‐mediated action. Addition of either an adenylate cyclase inhibitor or a protein kinase A (PKA) inhibitor reduced the mPACAP‐induced GTH‐II release. In addition, when GTH‐II release was already stimulated by either forskolin or 8‐bromo‐cAMP (8Br‐cAMP), mPACAP did not further increase GTH‐II secretion. These results strongly implicated the involvement of an adenylate cyclase/cAMP/PKA pathway in PACAP‐stimulated GTH‐II release. Although mPACAP induced a rise in intracellular Ca2+ level in identified gonadotropes, results with voltage‐sensitive Ca2+ channel inhibitors indicated that the GTH‐II responses to mPACAP, forskolin and 8Br‐cAMP did not depend upon Ca2+ entry through these channels. Two protein kinase C (PKC) inhibitors did not affect mPACAP‐elicited GTH‐II release, and mPACAP further increased GTH‐II secretion in the presence of PKC activators. These results indicate that PKC‐dependent elements are not essential for the stimulatory action of mPACAP in gonadotropes. Interestingly, while GTH‐II responses to a stimulatory concentration of mPACAP were additive to responses elicited by maximal effective concentrations of two endogenous gonadotropin releasing hormones (GnRHs), a subthreshold concentration of mPACAP potentiated GnRH and PKC activator stimulation of GTH‐II secretion. Similarly, submaximal concentrations of forskolin potentiated the GTH‐II response to the PKC activator, tetradecanoyl phorbol acetate. These data suggest that PACAP and its cAMP‐dependent signalling mechanisms provide an alternate stimulatory input to goldfish gonadotropes and may influence the effectiveness of the major neuroendocrine control exerted by the PKC‐dependent GnRH signalling pathway.
Tamoxifen Diminishes Methamphetamine‐Induced Striatal Dopamine Depletion in Intact Female and Male Mice
Authors: Dluzen D. E. , McDermott J. L. , Anderson L. I. 
Published: March 2003

AbstractIt has been demonstrated that the nigrostriatal dopaminergic system of male mice is more sensitive to the neurotoxic effects of methamphetamine (MA). The basis for this difference can be related to oestrogen, which has the capacity to function as a neuroprotectant against neurotoxins that target the nigrostriatal dopaminergic system. We examined the effects of the anti‐oestrogen, tamoxifen (TMX), upon MA‐induced neurotoxicity of the nigrostriatal dopaminergic system in intact female and male CD‐1 mice. Striatal dopamine concentrations of TMX‐treated female and male mice receiving MA were significantly greater than mice receiving MA alone. In female, but not male, mice, oestrogen treatment also resulted in greater striatal dopamine concentrations compared to mice receiving MA alone. Interestingly, male mice treated with oestrogen were particularly sensitive to the acute toxic effects of MA and displayed no evidence of nigrostriatal neuroprotection. The dihydroxyphenylacetic acid/dopamine ratios following MA for female and male mice treated with TMX or females treated with oestrogen were significantly reduced compared to MA‐treated mice and oestrogen + MA‐treated male mice. No differences among the treatment groups were obtained for dopamine in the hypothalamus or olfactory bulb. These data demonstrate that TMX treatment of intact female and male mice diminishes striatal dopamine depletions to the nigrostriatal dopaminergic neurotoxin, MA. Oestrogen also displayed this capacity when administered to female, but accentuated acute toxicity in male mice. These effects are relatively specific for the nigrostriatal dopaminergic system. Such data suggest that TMX can function as a nigrostriatal dopaminergic neuroprotectant against MA‐induced neurotoxicity in intact female and male mice.
Serotonergic Neurones in the Dorsal Raphe Nucleus That Project into the Medial Preoptic Area Contain Oestrogen Receptor β
Authors: Lu H. , Ozawa H. , Nishi M. , Ito T. , Kawata M. 
Published: March 2003

AbstractSerotonin is involved in female sexual behaviour in which the medial preoptic area (MPA) has a pivotal role. The present study used immunohistochemistry, in situ hybridization and retrograde transport analysis to investigate whether serotonin neurones in the dorsal raphe nucleus (DRN) of females projecting into the MPA contained oestrogen receptor α or β. The projection of serotonin neurones from the DRN to the MPA was confirmed using the microinjection of Fluoro‐Gold (FG), a fluorescent retrograde tracer, into the MPA of ovariectomized (OVX‐group) and OVX‐rats treated with oestradiol benzoate (E2‐group). A number of serotonin neurones in the DRN were labelled with FG, indicating that these serotonin neurones in DRN project their terminals into the MPA. FG‐labelled serotonin neurones expressed ERβ mRNA in the DRN, and the number of the serotonin neurones containing ERβ mRNA between the OVX‐group and the E2‐treated group was not significantly different. Serotonin neurones in the DRN did not express ERα‐immunoreactivity. Since previous findings showed that the density of serotonin‐immunoreactive fibres and the concentration of serotonin within the MPA was significantly lower in the E2‐group than the OVX‐group, our present observations suggested that the regulatory effects of E2 on the serotonergic neurone system in the MPA may be via ERβ within the serotonin‐containing cells in the DRN of female rats.
Oestradiol Increases Phosphorylation of a Dopamine‐ and Cyclic AMP‐Regulated Phosphoprotein (DARPP‐32) in Female Rat Brain
Authors: Auger A. P. , Meredith J. M. , Snyder G. L. , Blaustein J. D. 
Published: March 2003

AbstractRecent studies suggest that oestrogen and progestin receptors may be activated by the neurotransmitter dopamine, as well as by their respective ligands. Because intracerebroventricular infusion of D1, but not D2, dopaminergic receptor agonists increases oestrous behaviour in oestradiol‐primed rats, we wanted to determine if treatment with oestradiol alters the activity of D1 receptor‐associated processes in steroid receptor‐containing areas in female rat brain. One D1 receptor‐associated phosphoprotein that may be influenced by oestradiol is a dopamine‐ and cyclic AMP‐regulated phosphoprotein, Mr = 32 000 (DARPP‐32). Because DARPP‐32 is phosphorylated in response to dopamine acting via a cAMP‐dependent protein kinase, it provides a useful marker to examine where in the brain a particular stimulus might be altering the activity of D1 receptor‐containing neurones. To determine if oestradiol alters the phosphorylation of DARPP‐32, we stained immunocytochemically brain sections of female rats treated with behaviourally relevant doses of oestradiol or oil vehicle with an antibody that detects only the threonine 34‐phosphorylated form of DARPP‐32. Behaviourally effective doses of oestradiol increase the phosphorylation of DARPP‐32 within the medial preoptic nucleus, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and the ventromedial nucleus of the hypothalamus, 48 h after treatment. These data suggest that oestradiol increases the activity of D1 dopamine receptor‐associated processes in oestrogen receptor‐containing areas of female rat forebrain.
Photoperiodic Control of the Concentration of Luteinizing Hormone, Prolactin and Testosterone in the Male Emu (Dromaius novaehollandiae), a Bird that Breeds on Short Days
Authors: Blache D. , Talbot R. T. , Blackberry M. A. , Williams K. M. , Martin G. B. , Sharp P. J. 
Published: March 2003

AbstractThe objective of this study was to establish, for a short‐day breeding bird, the male emu, whether the breeding season is principally controlled by changes in photoperiod, and to investigate the endocrine mechanisms involved. Two groups of adult males were subjected to three alternating periods of 150–185 days of 14 h light/day (LD) and 10 h light/day (SD) terminating in a 360‐day period of LD or SD. Transfer from LD to SD led to increases in plasma concentrations of luteinizing hormone (LH) and testosterone, after 82 ± 8 and 73 ± 3 (SEM) days, and an increase in prolactin concentrations after 115 ± 12 days. Concentrations of LH and testosterone began to decrease before transfer back to LD, at a time when prolactin concentrations were approaching peak values. Transfer from LD to 360 days of SD resulted in increases in LH and testosterone concentrations, and these terminated after an increase in prolactin concentrations. After transfer from SD to 360 days of LD, plasma concentrations of LH and testosterone began to increase, after delays of 222 ± 24 and 225 ± 13 days, and were high at the end of the study, while prolactin values remained depressed throughout. These observations clearly show that seasonal breeding in the emu is directly controlled by changes in photoperiod. The dynamics of the hormonal responses to change of photoperiod suggest that, despite being short‐day breeders, the photoregulation of breeding in emus involves mechanisms that are currently accepted for birds, rather than mechanisms that have been proposed for short‐day breeding mammals. The initiation of breeding in emus is due to dissipation of photorefractoriness by short days which leads to an increase in the secretion of gonadotrophins to levels that are sufficient to support full reproductive condition. The termination of breeding, while days are still short, is due to the antigonadotrophic action of prolactin which, unusually for birds, increases while the days are still short. In conclusion, breeding activity in male emus is strongly controlled by photoperiod. Emus are short‐day breeders, but the central mechanisms that regulate the secretion of reproductive hormones seem to be similar to those previously proposed for long‐day breeding birds. The pattern of prolactin secretion in emus suggests an important role for this hormone in the termination of the breeding cycle.
Changes in Basal Hypothalamic Chicken Gonadotropin‐Releasing Hormone‐I and Vasoactive Intestinal Polypeptide Associated with a Photo‐Induced Cycle in Gonadal Maturation and Prolactin Secretion in Intact and Thyroidectomized Starlings (Sturnus vulgaris)
Authors: Dawson A. , Talbot R. T. , Dunn I. C. , Sharp P. J. 
Published: March 2003

AbstractChicken gonadotropin‐releasing hormone‐I (GnRH‐I) and the avian prolactin‐releasing hormone, vasoactive intestinal polypeptide (VIP), were measured in the basal hypothalamus in male starlings during photo‐induced gonadal growth and the subsequent development and maintenance of reproductive photorefractoriness. Comparisons were made with thyroidectomized birds, which maintain breeding condition irrespective of changes in photoperiod. In intact birds, basal hypothalamic GnRH‐I increased four‐fold after photostimulation and then decreased 115‐fold over 12 weeks to values characteristic of long‐term photorefractoriness. Pituitary and plasma prolactin increased after photostimulation, reaching peak values when the testes were regressing, and returned to low values in long‐term photorefractory birds. Basal hypothalamic VIP did not change after photostimulation in intact birds. In photostimulated thyroidectomized birds, values for basal hypothalamic GnRH‐I and VIP, and for pituitary and plasma prolactin, remained no different to those of nonphotostimulated intact birds. These observations confirm that reproductive photorefractoriness is related to a decrease in hypothalamic GnRH‐I. However, photorefractoriness in terms of prolactin secretion is not similarly related to a decrease in basal hypothalamic VIP. The mechanisms responsible for the decrease in prolactin in long‐term photorefractory birds and for the total lack of photoperiodic responses in thyroidectomized birds remain unresolved.
Involvement of cAMP‐Response Element Binding Protein in Corticotropin‐Releasing Factor (CRF)‐Induced Down‐Regulation of CRF Receptor 1 Gene Expression in Rat Anterior Pituitary Cells
Authors: Kasagi Y. , Horiba N. , Sakai K. , Fukuda Y. , Suda T. 
Published: March 2003

AbstractCorticotropin‐releasing factor (CRF) is a major secretagogue of adrenocorticotopic hormone from the anterior pituitary and a key activator of the hypothalamic‐pituitary‐adrenal axis. We previously reported that CRF down‐regulates expression of the CRF type‐1 receptor (CRF‐R1) mRNA in cultured rat anterior pituitary cells. The present study was conducted to clarify the signal transduction systems involved in CRF‐induced down‐regulation of CRF‐R1 gene expression in the anterior pituitary. Northern blot analysis revealed that, under serum‐free conditions, 10 nM CRF decreased CRF‐R1 mRNA levels in cultured rat anterior pituitary cells as we reported previously. Treatment with 5 mM 8‐Br‐cAMP reduced CRF‐R1 mRNA levels within 2 h. The mRNA level fell to 37±3% of the basal level at 2 h and remained low for 16 h after treatment. This CRF‐induced reduction of CRF‐R1 mRNA expression was inhibited completely by pretreatment with protein kinase A (PKA) inhibitor (1 µM H‐89). Further examination revealed that after pretreatment with 10 µM of antisense oligodeoxynucleotide for cyclic AMP‐response element binding protein (CREB), the CRF‐induced inhibition of CRF‐R1 mRNA was partially decreased to 79±4% of the control level 2 h after administration of CRF. These findings indicate that CRF may down‐regulate CRF‐R1 mRNA expression via a cAMP‐PKA‐mediated mechanism in rat anterior pituitary cells, and that CREB may mediate at least a portion of this inhibitory effect.
Autophagy in Hypothalamic Neurones of Rats Expressing a Familial Neurohypophysial Diabetes Insipidus Transgene
Authors: Davies J. , Murphy D. 
Published: March 2003

AbstractWe have tested the hypothesis that familial neurohypophysial diabetes insipidus (FNDI) is initiated by a process of autophagy. FNDI is a dominant, progressive inherited disorder characterized by pronounced drinking and urination caused by loss of secretion of antidiuretic hormone (vasopressin). In rats expressing an FNDI mutant transgene (Cys67stop) in vasopressin magnocellular neurones, the mutant protein fails to enter the regulated secretory pathway, and accumulates in a swollen and distended endoplasmic reticulum (ER) that also contains wild‐type, endogenous vasopressin. Transmission electron microscopy suggested that these are autophagic vesicles. We have now examined the expression of vesicular markers in our transgenic rats, and demonstrate that activation of autolysosomal processes is a consequence of the expression of Cys67stop. Swollen vesicles containing Cys67stop are immunoreactive for cathepsin D (a lysosomal protease), endolyn (a marker of late endosomes) and lysosomal associated membrane protein 1, suggesting that they may be degradative autolysosomes. In addition, there is an up‐regulation of lysosomal markers specifically in cells expressing Cys67stop. The expression of Cys67stop affects neither the trans‐Golgi network nor early endosomes. These data support the proposal that Cys67stop mutant protein aggregates within the ER, which is targeted for lysosomal degradation by autophagy.
Lack of Effect of Testosterone and Dihydrotestosterone Compared to 17β‐Oestradiol in 1‐Methyl‐4‐Phenyl‐1,2,3,6, Tetrahydropyridine‐Mice
Authors: Ekue A. , Boulanger J.‐F. , Morissette M. , Di Paolo T. 
Published: March 2003

AbstractPrevious work from our laboratory has demonstrated prevention of 1‐methyl‐4‐phenyl‐1,2,3,6, tetrahydropyridine (MPTP)‐induced striatal dopamine depletion in C57Bl/6 mice by 17β‐oestradiol, progesterone and raloxifene. The activity of androgenic compounds in MPTP mice has received less attention and was the object of the present investigation. The effects of 17β‐oestradiol (2 µg/day), testosterone (100 µg/day) and dihydrotestosterone (DHT) (2 µg/day or 100 µg/day) were studied during 5 days before and after an acute treatment of four MPTP (10 mg/kg) injections in male C57Bl/6 mice. Striatal concentrations of dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid were measured by high‐performance liquid chromatography. MPTP mice treated with saline showed large decreases in dopamine and its metabolites compared to control mice. 17β‐oestradiol partially spared this decrease whereas testosterone and DHT did not. Striatal specific binding to the dopamine transporter (DAT) and to the vesicular monoamine transporter (VMAT2) were measured using [125I] RTI‐121 and [3H] dihydrotetrabenazine autoradiography, respectively. As with striatal dopamine concentrations, MPTP treatment caused a decrease in DAT and VMAT2 specific binding. 17β‐oestradiol partially spared this decrease, whereas androgens did not. In the substantia nigra, DAT mRNA was measured by in situ hybridization. MPTP treatment induced a significant, but smaller decrease in substantia nigra DAT mRNA than striatal DAT protein. In addition, 17β‐oestradiol completely prevented the MPTP‐induced decrease of DAT mRNA, whereas androgens did not. The present results show that androgens are unable to protect against MPTP‐induced dopaminergic toxicity.
Serotonergic Stimulation of Corticotropin‐Releasing Hormone and Pro‐Opiomelanocortin Gene Expression
Authors: Jørgensen H. , Knigge U. , Kjær A. , Møller M. , Warberg J. 
Published: March 2003

AbstractThe neurotransmitter serotonin (5‐HT) stimulates adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary gland via activation of central 5‐HT1 and 5‐HT2 receptors. The effect of 5‐HT is predominantly indirect and may be mediated via release of hypothalamic corticotropin‐releasing hormone (CRH). We therefore investigated the possible involvement of CRH in the serotonergic stimulation of ACTH secretion in male rats. Increased neuronal 5‐HT content induced by systemic administration of the precursor 5‐hydroxytryptophan (5‐HTP) in combination with the 5‐HT reuptake inhibitor fluoxetine raised CRH mRNA expression in the paraventricular nucleus (PVN) by 64%, increased pro‐opiomelanocortin (POMC) mRNA in the anterior pituitary lobe by 17% and stimulated ACTH secretion five‐fold. Central administration of 5‐HT agonists specific to 5‐HT1A, 5‐HT1B, 5‐HT2A or 5‐HT2C receptors increased CRH mRNA in the PVN by 15–50%, POMC mRNA in the anterior pituitary by 15–27% and ACTH secretion three‐ to five‐fold, whereas a specific 5‐HT3 agonist had no effect. Systemic administration of a specific anti‐CRH antiserum inhibited the ACTH response to 5‐HTP and fluoxetine and prevented the 5‐HTP and fluoxetine‐induced POMC mRNA response in the anterior pituitary lobe. Central or systemic infusion of 5‐HT increased ACTH secretion seven‐ and eight‐fold, respectively. Systemic pretreatment with the anti‐CRH antiserum reduced the ACTH responses to 5‐HT by 80% and 64%, respectively. It is concluded that 5‐HT via activation of 5‐HT1A, 5‐HT2A, 5‐HT2C and possibly also 5‐HT1B receptors increases the synthesis of CRH in the PVN and POMC in the anterior pituitary lobe, which results in increased ACTH secretion. Furthermore, the results indicate that CRH is an important mediator of the ACTH response to 5‐HT.
Neurosecretory and Non‐Neurosecretory Parvocellular Neurones of the Hypothalamic Paraventricular Nucleus Express Distinct Electrophysiological Properties
Authors: Luther J. A. , Daftary S. S. , Boudaba C. , Gould G. C. , Halmos K. Cs. , Tasker J. G. 
Published: March 2003

AbstractParvocellular neurones of the hypothalamic paraventricular nucleus (PVN) comprise neurosecretory and non‐neurosecretory subpopulations. We labelled neurosecretory neurones with intravenous injection of the retrograde tracer, fluoro‐gold, and recorded from fluoro‐gold‐positive and negative PVN parvocellular neurones in hypothalamic slices. Non‐neurosecretory parvocellular neurones generated a low‐threshold spike (LTS) and robust T‐type Ca2+ current, whereas neurosecretory neurones showed no LTS and a small T‐current. LTS neurones were located in non‐neurosecretory regions of the PVN, and non‐LTS neurones were located in neurosecretory regions of the PVN. These findings indicate that neurosecretory and non‐neurosecretory subtypes of parvocellular PVN neurones express distinct membrane electrical properties.
Further Delineation of the Sequences Required for the Expression and Physiological Regulation of the Vasopressin Gene in Transgenic Rat Hypothalamic Magnocellular Neurones
Authors: Davies J. , Waller S. , Zeng Q. , Wells S. , Murphy D. 
Published: March 2003

AbstractWe have introduced transgenes into rats with a view to defining genomic regions that mediate the cell‐specific and physiological regulation of the vasopressin gene. These transgenes consist of the rat vasopressin structural gene with a reporter inserted into exon III, flanked by different lengths of upstream and downstream sequences. 11‐VCAT‐3 is flanked by 11 kbp of upstream sequences and 3 kbp of downstream sequences. The previously described 5‐VCAT‐3 is flanked by 5 kbp of upstream and 3 kbp of downstream sequences. 3‐VCAT‐3 has 3 kbp of upstream and 3 kbp of downstream sequences, and 3‐VCAT‐0.2 is flanked by 3 kbp of upstream and 0.2 kbp of downstream sequences. All four transgenes elicit the same expression patterns; low basal expression is seen in the magnocellular supraoptic and paraventricular nuclei, and is negligible in the suprachiasmatic nucleus. Expression increases markedly in vasopressin magnocellular cells following dehydration. The sequences responsible for the cell‐specific expression and physiological regulation of our transgenes thus reside within the confines of the smallest construct studied, 3‐VCAT‐0.2.
Bisphenol A Increases Progesterone Receptor Immunoreactivity in the Hypothalamus in a Dose‐Dependent Manner and Affects Sexual Behaviour in Adult Ovariectomized Rats
Authors: Funabashi T. , Sano A. , Mitsushima D. , Kimura F. 
Published: March 2003

AbstractRecently, we reported that bisphenol A (BPA), an endocrine disrupter, increased progesterone receptor (PR) mRNA in the preoptic area (POA) in adult ovariectomized rats. In the present study, we examined whether BPA also induced expression of PR proteins in both the POA and the ventromedial hypothalamic nucleus (VMH), and whether those proteins were involved in the induction of sexual behaviour. Two weeks after ovariectomy, rats received a subcutaneous (s.c.) injection of BPA, 17β‐oestradiol or vehicle. Twenty‐four hours after the injection, the rats were killed and their tissues were examined by immunocytochemistry. Some rats that received a s.c. injection of BPA, E2 or vehicle alone on the day before were injected with progesterone at 15.00 h and examined for sexual behaviour 5–7 h later. As expected, injection of 10 µg E2 significantly increased the number of PR immunoreactive cells in both the POA and the VMH compared to the number after injection of vehicle alone. In both the POA and the VMH, injection of BPA at a dose of 10 mg also significantly increased the number of PR immunoreactive cells compared to the number after injection of sesame oil alone. Furthermore, BPA induced a dose‐dependent increase in the number of PR immunoreactive cells in both the POA and the VMH, demonstrating that the number of PR cells was significantly increased by as little as 100 µg of BPA. Ovariectomized (OVX) rats that were primed with 10 mg of BPA, followed by 1 mg of progesterone, displayed mainly rejection behaviour, but not lordosis as typically observed in OVX rats primed with E2 followed by progesterone. The present study suggests that BPA influences reproductive functions, including sexual behaviour even in adulthood, by altering the PR system in the hypothalamus.