bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of the Gonadotropic Axis by the Neuropeptide Y Receptor Y1 Antagonist/ Y4 Agonist 1229U91 in the Male Rat
Authors: Raposinho Paula D. , Broqua Pierre , Hayward Amanda , Akinsanya Karen , Galyean Robert , Schteingart Claudio , Junien Jean-Louis , Aubert Michel L. 
Published: April 2003

Neuropeptide Y (NPY) is a highly potent orexigenic substance that is also known to modulate gonadotropin secretion. Five receptor subtypes for NPY have been identified, and a potent antagonist for the receptor subtype 1 (Y1), 1229U91, also known as GW1229 or GR231118, has been described. Subsequently, 1229U91 was also shown to represent a highly potent agonist for the Y4 receptor subtype. Very unexpectedly, intracerebroventricular administration of 1229U91 elicited an intense, dose-dependent surge of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact male rats that lasted for 6 h. Such stimulation was absent when a potent gonadotropin-releasing hormone antagonist was administered systemically, suggesting that 1229U91 acts centrally to stimulate gonadotropin-releasing hormone release. 1229U91 administration had no effect on growth hormone, thyroid-stimulating hormone, and corticosterone secretions. In addition to 1229U91, four other parent dimer molecules described earlier produced a marked and sustained stimulation of LH when injected intracerebroventricularly that was proportional to their binding affinity for the Y4 receptor. Central administration of the specific Y1 antagonist BIBO3304 (20 µg) had no effect on LH secretion, making it unlikely for 1229U91 to stimulate LH secretion by an antagonistic action on the Y1 receptor subtype, thus suggesting a Y4 receptor mediation. In conclusion, the 1229U91 molecule displays an interesting conformational epitope that is able to generate large LH surges, possibly by activating Y4 or Y4-like receptor subtypes or by acting on a NPY receptor unrelated target.
Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretion Is an Inherent Function of GnRH Neurons, as Revealed by the Culture of Medial Olfactory Placode Obtained from Embryonic Rats
Authors: Funabashi Toshiya , Daikoku Shigeo , Shinohara Kazuyuki , Kimura Fukuko 
Published: April 2003

To determine whether gonadotropin-releasing hormone (GnRH) neurons in culture without the hypothalamus secrete GnRH in a pulsatile fashion, the nasal placode (NAP) was obtained at day 13.5 of gestation and cultured by a roller tube method. If the GnRH release occurs in a pulsatile fashion, it can be said that the pulse generator of GnRH exists inherently in each cell or community of cells in the culture. The concentration of GnRH in the NAP culture medium collected at 8-min intervals for 160 min after 2- to 4-week cultures showed that GnRH release occurred in a pulsatile fashion with a mean interpulse interval of 29.8 ± 2.3 min (n = 9). When the NAP was cultured with tissues of the forebrain vesicle (n = 3) or the hypothalamus (n = 4), GnRH was also released in a pulsatile fashion with similar intervals (27.3 ± 1.0 min for the NAP+forebrain vesicle culture and 36.0 ± 6.3 min for the NAP+hypothalamus culture) as those in cultures without brain tissues. It is concluded that pulsatile GnRH release is an inherent function of GnRH neurons.
Oxytocin/Alpha<sub>2</sub>-Adrenoceptor Interactions in Feeding Responses
Authors: Díaz-Cabiale Zaida , Narváez José A. , Petersson Maria , Uvnäs-Moberg Kerstin , Fuxe Kjell 
Published: April 2003

The modulation of α<sub>2</sub>-adrenoceptor-induced food intake by oxytocin has been evaluated in studies on food intake and by quantitative receptor autoradiography in the hypothalamus and the amygdala of the rat. The effects of lateral intracerebroventricular administration of clonidine and oxytocin were evaluated on food intake in satiated animals. Food consumption was measured at 30, 90, 240 min and 22 h (1,320 min) after injection. The coinjection of oxytocin and clonidine was found to counteract the increase in food intake produced by clonidine (p < 0.001) in satiated rats. Receptor autoradiographic experiments showed that oxytocin significantly increased the K<sub>d</sub> values of [<sup>3</sup>H]<i>p</i>-aminoclonidine α<sub>2</sub>-agonist-binding sites in the hypothalamus. Effective oxytocin concentrations ranged between 0.3 and 1 n<i>M</i> (p < 0.05) with a maximal action of 250% at 1 n<i>M</i>. The B<sub>max</sub> value was significantly increased (p < 0.05) for all concentrations of oxytocin. In the amygdala, oxytocin also increased both the K<sub>d</sub> of [<sup>3</sup>H]<i>p</i>-aminoclonidine-binding sites by about 190% at 1 n<i>M</i> and the B<sub>max</sub> values at 1 and 3 n<i>M</i> (p < 0.05). Oxytocin (1 n<i>M</i>) also significantly and substantially (p < 0.01) increased the K<sub>d</sub> and B<sub>max</sub> values of the [<sup>3</sup>H]UK 14.304 α<sub>2</sub>-agonist-binding sites in the hypothalamus and amygdala in agreement with the results obtained with the other agonist of the α<sub>2</sub>-adrenoceptor [<sup>3</sup>H]<i>p</i>-aminoclonidine. This effect was partially blocked by the presence of the specific oxytocin receptor antagonist, CAP. These findings suggest the existence of an antagonistic oxytocin/α<sub>2</sub>-receptor interaction in the hypothalamus and amygdala that may be of relevance for the demonstrated modulation of α<sub>2</sub>-adrenoceptor-induced feeding responses by oxytocin.
Immunoneutralization of Endogenous Opioid Peptides Prevents the Suckling-Induced Prolactin Increase and the Inhibition of Tuberoinfundibular Dopaminergic Neurons
Authors: Callahan Phyllis , Klosterman Shannon , Prunty Danielle , Tompkins Janine , Janik James 
Published: April 2003

Previous studies have shown that the endogenous opioid peptides, acting at specific opiate receptor subtypes, are involved in the suckling-induced prolactin secretory response. The prolactin increase elicited by suckling is due, at least in part, to an inhibition of tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus. We investigated the effects of immunoneutralization of dynorphin, leu-enkephalin and met-enkephalin on the suckling-induced prolactin increase and on the activity of the TIDA neurons in lactating female rats between days 7 and 12 postpartum. Rats were injected into the right lateral ventricle with antiserum specific for one of these three peptides. Control rats were administered equal amounts of immunoglobulin proteins. Suckling produced a profound and significant increase in prolactin levels, as well as a decrease in DOPA accumulation in the median eminence of lactating rats. Administration of immunoglobulin concentrations of up to 3.6 µg did not inhibit the prolactin secretory response to the suckling stimulus and did not prevent the suckling-induced inhibition of TIDA neurons. Antisera to all three endogenous opioid peptides abolished the suckling-induced prolactin increase and prevented the inhibition in DOPA accumulation in the median eminence. Thus, the endogenous opioid peptides, dynorphin, leu-enkephalin and met-enkephalin, are essential for the prolactin secretory response to suckling and inhibition of TIDA neuronal activity is at least one of the mechanisms of action utilized by these peptides.
Regulation of C-fos Protein in Gonadotrope Cells by Oxytocin and Gonadotropin-Releasing Hormone
Authors: Abbas Maysoon M. , Evans John J. 
Published: April 2003

The integrated regulation of luteinizing hormone (LH) from the anterior pituitary gland is vital to the functioning of the ovulatory cycle in the female and consists of several components acting at different time points. The best-studied is the rapid release of LH elicited by gonadotropin-releasing hormone (GnRH). The so-called primary (immediate early) response genes (PRGs), including c-fos, regulate relatively long-term activities, such as mitosis, protein synthesis, protein release and cell differentiation. Regular ovulatory cycles occur as a result of interaction of several peptide factors including the primary factor, GnRH and oxytocin, although GnRH and oxytocin do not have identical activities. We wished to determine whether oxytocin could mediate changes in expression of c-fos protein and compare its effects with those of GnRH. Anterior pituitary glands were collected from female rats at proestrus and a single-cell suspension prepared. Cells were incubated with oxytocin or GnRH at selected concentrations for various times. C-fos protein was extracted and submitted to Western blot analysis. Other cells were stained immunohistochemically for c-fos and LH following incubation with the peptides and fixation. There was an increase in c-fos protein from 15 to 60 min in Western blots of cells from all incubations. After immunohistochemistry, it was observed that both oxytocin (100 n<i>M</i>) and GnRH (100 n<i>M</i>) increased the percentage of cells that expressed c-fos protein (p < 0.001) and of cells that expressed LH (p < 0.001). The responses to the peptides were concentration dependent. We found that neither all LH-containing cells expressed c-fos, nor all c-fos-containing cells immunostained for LH. The effects of the peptides were not the same. High concentrations of GnRH (1 µ<i>M</i>) induced the appearance of a higher percent of LH-containing cells having c-fos than did 10 n<i>M</i> GnRH (p < 0.01), whereas a lower percent of LH-containing cells with c-fos were observed when the oxytocin concentration was raised from 10 n<i>M</i> to 1 µ<i>M</i> (p < 0.02). It appears, therefore, that the two peptides have different regulatory effects on LH-containing cells, indicating the possibility of specialized function. The results emphasize the suggestion that stimulation of LH secretion is not the sole index of gonadotrope-directed activity by a peptide. Collectively, these results indicate that the peptides oxytocin and GnRH are able to modulate processes that are associated with longer-term activities of gonadotropes and also demonstrate that specific subpopulations of LH-containing gonadotropes are stimulated to express c-fos.
Blockage of N-Methyl-<i>D</i>-Aspartate Receptors Decreases Testosterone Levels and Enhances Postnatal Neuronal Apoptosis in the Preoptic Area of Male Rats
Authors: Hsu Chin , Hsieh Ya-Lun , Yang Rei-Cheng , Hsu Hseng-Kuang 
Published: April 2003

Sexual dimorphism has been found in the preoptic area of the hypothalamus (POA), a major site of glutamate actions via N-methyl-<i>D</i>-aspartate (NMDA) receptors. The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats exhibits about seven-fold greater nuclear volume than that of females. A naturally occurring neonatal neuronal apoptosis, that can be prevented by testosterone, may contribute to this sexual difference in SDN-POA nuclear volume. Since activation of NMDA receptors in the POA induces GnRH secretion, it may be involved in both elevation of serum testosterone and prevention of neuronal death in the SDN-POA. In the present study, protein expression of NMDA receptors in the POA of male and female fetuses was quantified on the day preceding the fetal testosterone peak (embryonic day 16; ED 16). Rats were then distributed in four groups: (1) untreated males, (2) untreated females, (3) males pretreated with MK-801 (a noncompetitive NMDA receptor antagonist), and (4) females pretreated with MK-801. Serum levels of testosterone were estimated on the afternoon of ED 18. Expression of Bcl-2 and Bax, as well as neuronal apoptosis in SDN-POA, were observed on postnatal day 8. The results showed that (1) expression of NMDA receptors in the POA of male fetuses was higher than that of females on ED 16; (2) levels of testosterone were lower in MK-801 pretreated male fetuses than in intact males on ED 18; (3) expression of Bcl-2 in the POA of MK-801 pretreated male rats was significantly less than that of control males; (4) the apoptotic incidence in the SDN-POA of MK-801 pretreated male rats was significantly greater than in control males, while there was no significant difference in apoptotic incidence in the SDN-POA between MK-801 pretreated and intact females. These results suggest that the NMDA receptor is highly expressed in prenatal male fetuses, and that it might play an important role in the elevation of testosterone levels. Moreover, activation of NMDA receptors may protect SDN-POA neurons from naturally occurring neuronal death, by modulating testosterone and/or Bcl-2 expression.
Prenatal Glucocorticoid Modifies Hypothalamo-Pituitary-Adrenal Regulation in Prepubertal Guinea Pigs
Authors: Dean Farrah , Yu Catherine , Lingas Rania I. , Matthews Stephen G. 
Published: April 2003

We hypothesized that exposure to synthetic glucocorticoid during rapid brain growth (d50–52, birth = 68 days) in fetal guinea pigs modifies hypothalamo-pituitary-adrenal (HPA) function after birth, and that this involves changes in central corticosteroid receptor regulation. On the basis of our previous studies, we proposed that this effect is sex-specific. Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on d50–51 of gestation, and juvenile offspring were euthanized at rest or following isolation stress on postnatal day 18. Dexamethasone increased the length of gestation (1.5 days) and altered body and organ (brain, heart, adrenal) growth. Resting plasma cortisol concentrations were significantly elevated in young male, but not female guinea pigs exposed to dexamethasone as fetuses. In female offspring born to dexamethasone-treated mothers, cortisol responses to isolation stress were attenuated. In males, elevated basal cortisol levels were not increased further by isolation. In the brain, hippocampal glucocorticoid receptor (GR) mRNA levels were significantly lower (10–25%) in females exposed to dexamethasone in utero. In contrast, GR mRNA levels were elevated (10–20%) in males from this prenatal treatment group. Mineralocorticoid receptor mRNA in the limbic system and GR mRNA levels in the pars distalis were unaffected. Pro-opiomelanocortin mRNA was significantly lower (30%) in the male pars intermedia following dexamethasone exposure. In conclusion, prenatal glucocorticoid exposure affects growth and HPA function as well as limbic and hypothalamic GR expression in juvenile offspring, and these effects are highly sex-specific.
Oral Testosterone Self-Administration in Male Hamsters
Authors: Johnson Luke R. , Wood Ruth I. 
Published: April 2003

The addiction potential of anabolic steroids remains largely unexplored. Here, we demonstrate voluntary oral testosterone intake in hamsters. Using a 2-bottle choice test, males preferred an aqueous solution of 200 µg/ml testosterone over vehicle. However, the taste of testosterone is not highly preferred. Addition of testosterone at 400 µg/ml increased fluid consumption from the nonpreferred bottle in a 2-bottle choice test, but cholesterol at the same concentration reduced drinking, suggesting that testosterone reward is not common to all sterols. With food-induced drinking, testosterone maintained fluid intake when food was withdrawn. These data demonstrate that oral self-administration of testosterone is reinforcing in hamsters, suggesting the potential for dependence in human users.
Hypothalamo-Pituitary-Adrenal Axis Activity Is Related to the Level of Central Arousal: Effect of Sleep Deprivation on the Association of High-Frequency Waking Electroencephalogram with Cortisol Release
Authors: Chapotot Florian , Buguet Alain , Gronfier Claude , Brandenberger Gabrielle 
Published: April 2003

The temporal and quantitative interrelationships between the hypothalamo-pituitary-adrenal (HPA) axis activity and the level of central arousal were studied in 10 healthy young men during daytime wakefulness. Two experimental sessions were conducted randomly between 09.00 and 18.00 h, once after nocturnal sleep and once after a night of total sleep deprivation. Spectral analysis of serial waking electroencephalography (EEG) from a short target fixation task repeated every 10 min was undertaken, along with an estimation of cortisol secretory profiles by deconvolution of plasma radioimmunoassay measures obtained from continuous blood withdrawal with regular sampling at a 10-min interval. Following nocturnal sleep, a temporal association between the HPA axis activity and the waking EEG activity was found, cortisol secretory rate following changes in frontal gamma (20–45 Hz) band power by 10 min (average R = 0.458, p < 0.001). Although it remained significant (average R = 0.276, p < 0.05), the association strength decreased significantly following total sleep deprivation (p < 0.05, Wilcoxon test). Cortisol plasma level, secretory rate and pulse amplitude were increased as well as waking EEG power in the delta (0.5–5.5 Hz), theta (5.5–8.5 Hz) and gamma frequency bands (all p values <0.05, Student t tests). The sleep deprivation-related increases in cortisol secretory rate and waking EEG gamma activity were quantitatively associated (R = 0.504, p < 0.05). These results support the existence of a common ultradian regulatory mechanism, co-ordinating HPA axis activity to the level of central arousal in man, which seems involved in the sleep deprivation-induced hyperarousal.
GABA<sub>B</sub> Receptors in Anterior Pituitary Cells
Authors: Lux-Lantos Victoria , Becú-Villalobos Damasia , Bianchi María , Rey-Roldán Estela , Chamson-Reig Astrid , Pignataro Omar , Libertun Carlos 
Published: April 2003

The activation of pituitary GABA<sub>B</sub> receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABA<sub>B</sub> receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal studies and cAMP determination or incubated in FURA 2AM for calcium measurements. Baclofen (BACL: 1·10<sup>–5</sup> <i>M</i>) significantly inhibited basal and thyrotropic releasing hormone (TRH)-stimulated (1·10<sup>–7</sup> <i>M</i>) PRL secretion in anterior pituitary cells from proestrous rats. In the presence of pertussis toxin (PTX: 150 ng/ml, 20 h), which leads to the uncoupling of the G<sub>i/o</sub>-protein from the receptor, both effects of BACL were abolished while the effect of dopamine (DA: 1·10<sup>–8</sup> <i>M</i>), used as an inhibitory control, was reduced from 70 to 25%. PTX also reversed BACL-induced inhibition of gonadotropin-releasing hormone (GnRH)-elicited luteinizing hormone (LH) secretion in anterior pituitary cells from 15-day-old female rats. In addition, though working in a pituitary mixed cell population, in which only some cell types possess GABA<sub>B</sub> receptors, BACL (1·10<sup>–5</sup> <i>M</i>) attenuated the forskolin-induced (0.5 µ<i>M</i>) increase in cAMP. This effect was prevented by co-incubation with the antagonist 2 hydroxysaclofen and by preincubation with PTX. BACL (5· 10<sup>–5</sup> <i>M</i>) and DA (5·10<sup>–7</sup> <i>M</i>) inhibited basal intracellular calcium concentrations ([Ca<sup>2+</sup>]<sub>i</sub>) in pituitary cells and the effect of the latter was significantly stronger. The effect of BACL on [Ca<sup>2+</sup>]<sub>i</sub> was abolished after preincubation with PTX. In the presence of the potassium channel blocking agents barium (200 µ<i>M </i>and 1 m<i>M</i>) and tetraethylammonium (10 m<i>M</i>), BACL was still able to inhibit [Ca<sup>2+</sup>]<sub>i</sub>. Blockade of voltage-sensitive calcium channels (VSCC) with either verapamil (5·10<sup>–6</sup> <i>M</i>) or nifedipine (1·10<sup>–6</sup> <i>M</i>) completely abolished the effect of BACL on [Ca<sup>2+</sup>]<sub>i</sub>. In the presence of 12.5 m<i>M</i> potassium concentration baclofen significantly inhibited [Ca<sup>2+</sup>]<sub>i</sub>. In conclusion, our results describe the negative coupling of adenohypophyseal GABA<sub>B</sub> receptors to VSCC through PTX-sensitive G-proteins. These characteristics suggest a resemblance of these receptors to the typical presynaptic GABA<sub>B</sub> sites described in the central nervous system.
Sensitivity to a Neurosteroid Is Increased during Addition of Progestagen to Postmenopausal Hormone Replacement Therapy
Authors: Wihlbäck Anna-Carin , Sundström-Poromaa Inger , Nyberg Sigrid , Bäckström Torbjörn 
Published: April 2003

The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during different hormonal settings of postmenopausal hormone replacement therapy (HRT). Twenty-seven postmenopausal women with climacteric symptoms were administered HRT in a randomized, double-blinded, placebo-controlled crossover study. The women received 2 mg estradiol (E<sub>2</sub>) continuously during four 28-day cycles and 10 mg medroxyprogesterone acetate (MPA), 1 mg norethisterone acetate (NETA) or placebo sequentially for the last 14 days in each cycle. The pharmacodynamic response to pregnanolone was assessed before treatment and during the last week of each treatment, by comparing the effects of intravenous pregnanolone (3α-hydroxy-5β-pregnan-20-one) on saccadic eye velocity (SEV), saccade deceleration, saccade latency and self-rated sedation. Throughout the study daily symptom rating scales were kept. During the progesta gen phase of the treatment cycles, negative mood symptoms and physical symptoms were increased, whereas positive mood symptoms were decreased. Compared to pretretreatment conditions, E<sub>2</sub> alone did not change the responsiveness to pregnanolone. During progestagen addition to E<sub>2</sub>, the responsiveness to pregnanolone was increased. The sedation response increased compared to pretreatment conditions during both E<sub>2</sub> + MPA and E<sub>2</sub> + NETA treatment. Compared to E<sub>2</sub> treatment alone, addition of MPA increased the postpregnanolone effect on saccade deceleration, whereas the SEV response to pregnanolone was increased during E<sub>2</sub> + NETA treatment. It is concluded that pregnanolone sensitivity increases together with deterioration in mood symptoms during addition of progestagen to HRT.
Estrogen and Laryngeal Synaptic Strength in <i>Xenopus laevis:</i> Opposite Effects of Acute and Chronic Exposure
Authors: Wu Kwok Hang , Tobias Martha L. , Kelley Darcy B. 
Published: April 2003

Synaptic transmission at the vocal synapse, the laryngeal neuromuscular junction, of <i>Xenopus laevis </i>has been shown to be regulated by long-term changes in circulating estrogen. In females, high levels of circulating estrogen also accompany gonadotropin-induced ovulation and oviposition and the switch from sexually unreceptive to receptive states, including changes in vocal behaviors (ticking to rapping). Here we examine the effects of gonadotropin injection on laryngeal synaptic strength and call type. Gonadotropin acutely reduced quantal content values of laryngeal synapses in intact, adult females; the lowest values were attained by 12 h post-injection. Estrogen and progesterone levels increased following human chorionic gonadotropin (hCG) injection; the time course was similar to, but negatively correlated with, changes in synaptic strength. In ovariectomized frogs, exogenous estrogen, but not progesterone or hCG, mimicked the acute effects of hCG in weakening laryngeal synapses of intact frogs. hCG injection suppressed ticking and sometimes induced rapping. Females could tick with either strong or weakened laryngeal synapses while rapping was only produced during the weakening action of hCG. The normally strong synapses of females may enable vocal production even when laryngeal synapses are weakened by hormones that induce ovulation. In contrast to the acute effect of estrogen on weakening laryngeal synapses, juveniles required more than 2 weeks of estrogen treatment to strengthen laryngeal synapses while at least 4 weeks postovariectomy were required to weaken synapses in adult females. We conclude that acute (hours) increases in circulating levels of estrogen weaken synapses while chronic (weeks) increases strengthen laryngeal synapses.