bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semicircadian Rhythms of c-Fos Expression in Several Hypothalamic Areas during Pregnancy in the Rat: Relationship to Prolactin Secretion
Authors: Lee Youngsoo , Arbogast Lydia A. , Voogt James L. 
Published: April 2003

Prolactin (PRL) serves an important luteotrophic function in the rat during early pregnancy, expressed as a nocturnal surge in the early morning and a diurnal surge in the late afternoon. Several areas of the hypothalamus, including the preoptic area (POA), the suprachiasmatic nucleus (SCN) and the ventromedial and dorsomedial nuclei (VM-DM) have been implicated in PRL surges. We investigated the temporal relationship between neuronal activity as measured by c-Fos immunocytochemistry in these areas and PRL secretion during early and late pregnancy. Brains were collected at nine time points (24:00, 02:00, 04:00, 06:00, 10:00, 14:00, 16:00, 18:00 and 20:00 h) on days 6–7 and three time points (02:00, 14:00 and 18:00 h) on days 14–15 of pregnancy. Plasma PRL levels determined by radioimmunoassay revealed two surges with peaks at 02:00 and 18:00 h and a trough at 14:00 h on days 6–7, which were absent on days 14–15 of pregnancy. The number of neurons expressing c-Fos in the anterior medial preoptic nucleus, the medial preoptic area and the medial preoptic nucleus, but not the anteroventral preoptic nucleus of the POA, and the VM-DM, showed a semicircadian rhythm which was maximal at 02:00 h or/and 04:00 and 18:00 h and reached the lowest value at 14:00 h, in parallel with the PRL surges in early pregnancy. However, the temporal pattern of c-Fos in these areas was reversed during late pregnancy, with a peak at 14:00 h and low levels at 02:00 and 18:00 h. PRL surges were absent and levels were uniformly low during these times. Neuronal activity in the SCN did not show any correlation with PRL surges. The dorsomedial subdivision of the SCN showed high neuronal activity during the daytime in both stages of pregnancy. Neuronal activity in the ventrolateral subdivision of the SCN was high during the nighttime in early pregnancy, however it exhibited high levels during the daytime in late pregnancy. These results suggest that the two daily surges of PRL secretion during the first half of pregnancy might be related to the temporal rhythm of neuronal activity in the POA and the VM-DM, and a major change in the pattern of neuronal activity in these hypothalamic areas might result in termination of the PRL surges at midpregnancy.
Effect of Bacterial Endotoxin on in vivo Pulsatile Gonadotropin Secretion in Adult Male Rats
Authors: Refojo Damián , Arias Pablo , Moguilevsky Jaime A. , Feleder Carlos 
Published: April 2003

Immune system disorders are often accompanied by alterations in the reproductive axis. The bacterial endotoxin (lipopolysaccharide or LPS) has central inflammatory effects, and activates cytokine release (immune system mediatory factors) in the hypothalamus, where the luteinizing hormone-releasing hormone neurons are located. The present study was designed to investigate the effect of LPS on the pulsatile release of LH and FSH in adult male rats. With this aim, orchidectomized male rats were implanted with an atrial catheter and received, after two basal blood collections, LPS (250 µg/kg i.v.) or saline. Subsequently, blood samples were taken at regular intervals during 110 min. As expected, LH release was markedly reduced following exposure to LPS. In order to quantify these effects objectively, we subjected these data to PC-pulsar analysis. Pulsatile LH release was clearly disrupted in LPS-treated animals as compared to control rats: pulse frequency 1.3 ± 0.3 versus 0.43 ± 0.2/110 min, p < 0.05; pulse amplitude 17.18 ± 2.2 versus 8.33 ± 0.66 ng/ml, p < 0.05; overall mean release 15.2 ± 0.75 versus 7.08 ± 1.11 ng/ml, p < 0.001; maximum values 27.5 ± 3.08 versus 9.95 ± 2.16 ng/ml, p < 0.001; baseline levels 13.83 ± 0.77 versus 6.55 ± 0.74 ng/ml, p < 0.001. Regarding FSH secretion, LPS administration significantly lowered baseline levels (p < 0.05) and overall mean release (p < 0.01); FSH pulsatility parameters showed no significant differences. These observations indicate that LPS decreases LH and FSH mean release rates and baseline levels and inhibits several pulsatility parameters of LH release (frequency, amplitude and maximum values); FSH pulsatility parameters are not altered by LPS administration. We speculate that this effect is exerted principally at the hypothalamic level by modifying GnRH secretion.
Decrease of the Number of Opioid Receptors and of the Responsiveness to Morphineduring Neuronal Differentiation Induced by 17β-Estradiol in Estrogen Receptor-Transfected Neuroblastoma Cells (SK-ER3)
Authors: Maggi Roberto , Ma ZhiQing , Pimpinelli Federica , Maggi Adriana , Martini Luciano 
Published: April 2003

Estrogens modulate the density of opioid receptors in selected brain areas; however, it is not clear whether they exert such an effect directly on the cells which express the opioid receptors. Therefore, we analyzed the binding of [<sup>3</sup>H]-diprenorphine in human neuroblastoma cells stably transfected with the estrogen receptor cDNA (SK-ER3 cell line). A 16-hour exposure of these cells with 1 nM 17β-estradiol induces a progressive morphological differentiation which appears clearly established 6 days after the suspension of the treatment. The binding of [<sup>3</sup>H]-diprenorphine was then measured immediately after the exposure to 17β-estradiol (16 h) as well as 6 days later. The results shows that the number of opioid receptors in SK-ER3 cells is unaffected at 16 h but appears significantly reduced at 6 days. This effect is blocked by the estrogen antagonist ICI-182780, and is coincident to a decrease of the inhibitory effect of morphine on cyclic AMP accumulation. Binding experiments performed using selective ligands suggest that the µ subclass of opioid receptors is down-regulated by estradiol in SK-ER3 cells.
Intracerebroventricular Administration of Bromocriptine Ameliorates the Insulin-Resistant/Glucose-Intolerant State in Hamsters
Authors: Luo Shuqin , Liang Yin , Cincotta AnthonyH. 
Published: April 2003

Bromocriptine, a potent dopamine D<sub>2</sub> receptor agonist, suppresses lipogenesis and improves glucose intolerance and insulin resistance. Recent evidence suggests that bromocriptine may produce these effects by altering central nervous system (CNS) regulation of metabolism. To determine whether or not the CNS plays a critical role in these bromocriptine-mediated effects on peripheral metabolism, we compared the metabolic responses to bromocriptine when administered peripherally versus centrally in naturally obese and glucose intolerant Syrian hamsters. Male hamsters (BW 194 ± 5 g) were treated with bromocriptine or vehicle either intraperitoneally (i.p., 800 µg/animal) or intracerebroventricularly (i.c.v., 1 µg/animal) daily at 1 h after light onset for 14 days while held on 14-hour daily photoperiods. Glucose tolerance tests (GTTs, 3 g glucose/kg BW) were conducted after treatment. Compared to control animals, bromocriptine i.p. significantly reduced weight gain (11.7 vs. –2.4 g) and the areas under the glucose and insulin GTT curves by 29 and 48%, respectively. Similarly, compared with vehicle-treated controls, bromocriptine i.c.v. at 1 µg/animal substantially reduced weight gain (8.7 vs. –6.3 g), the areas under the glucose and insulin GTT curves by 31 and 44% respectively, and the basal plasma insulin concentration by 41% (p < 0.05). Furthermore, both treatments significantly improved insulin-mediated suppression of hepatic glucose production during a hyperinsulinemic-euglycemic clamp. Thus, daily administration of bromocriptine at a very low dose i.c.v. replicates the metabolic effects of bromocriptine administered i.p. at a much higher dose. This finding demonstrates for the first time that the CNS is a critical target of bromocriptine’s metabolic effects.
Long-Term Changes in Gastrin, Cholecystokinin and Insulin in Response to Oxytocin Treatment
Authors: Petersson Maria , Hulting Anna-Lena , Andersson Renée , Uvnäs-Moberg Kerstin 
Published: April 2003

The present study was designed to investigate how repeated injections of oxytocin influence plasma levels of vagally controlled hormones such as gastrin, cholecystokinin (CCK), insulin and somatostatin, as well as of endogenous oxytocin and glucose. Since oxytocin may enhance the activity of centrally located α<sub>2</sub>-adrenoreceptors, a second aim of this study was to explore whether these receptors are involved in the effects. For this purpose, oxytocin (1.0 mg/kg) or NaCl was given subcutaneously (s.c.) once a day during 5 days to male rats. Rats were decapitated 1, 3 and 10 days after the last injection, blood was collected and hormone levels were radioimmunoassayed. The oxytocin treatment caused an elevation of plasma levels of oxytocin 1 day (p < 0.05) but not 3 and 10 days after treatment. Gastrin levels were decreased on day 1, 3 and 10 (ANOVA; p < 0.01). In addition, both insulin and CCK levels were decreased in response to the oxytocin treatment when measured 3 and 10 days after the last injection (ANOVA; insulin p < 0.01, CCK p < 0.05). When the α<sub>2</sub>-adrenoreceptor agonist clonidine (2.5 µg/kg intracerebroventricularly) was administered 3 days after the 5-day treatment period with oxytocin or saline, plasma levels of insulin and CCK increased significantly (p < 0.05) in the oxytocin-treated rats, when compared to saline-treated controls receiving clonidine only. No change in glucose or somatostatin levels was found in response to the oxytocin treatment. In conclusion, these results show that oxytocin induces long-lasting changes in plasma levels of gastrin, CCK and insulin, without affecting somatostatin or glucose levels. These effects may be mediated by changes in vagal nerve activity.
Inhibition of Hormonally Induced Inositol Trisphosphate Production in Transfected GH<sub>4</sub>C<sub>1</sub> Cells: A Novel Role for the D<sub>5</sub> Subtype of the Dopamine Receptor
Authors: White BeatrixH. , Kimura Kazuhiro , Sidhu Anita 
Published: April 2003

We have previously found that the D<sub>5</sub> dopamine receptor couples to a G-protein other than G<sub>s</sub>α, and could be involved in signaling pathways other than regulation of adenylyl cyclase. To describe interactions of the D<sub>5</sub> receptor with cellular effectors, we used GH<sub>4</sub>C<sub>1</sub> cells transfected with cDNA for the human D<sub>5</sub> receptor. Thyrotropin-releasing hormone (TRH, 100 nM) stimulated accumulation of inositol phosphates (IPs) fivefold in D<sub>5</sub>GH<sub>4</sub>C<sub>1</sub> cells. Dopamine (DA, 10 µM) inhibited TRH-stimulated IP values by 29%; at higher concentrations (100 µM), maximal inhibition of 61% was observed. The D<sub>5</sub> agonist SKF R-38393 (10 µM) mimicked this effect (28% inhibition). SCH 23390, a D<sub>5</sub> antagonist, blocked the inhibition caused by both DA and SKF R-38393. Spiperone, a D<sub>2</sub> receptor antagonist, did not block the inhibition. The D<sub>2</sub> agonist (±)-2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin (PPHT) did not inhibit TRH-stimulated IP production, nor did it augment the effect of D<sub>5</sub> agonists. The DA-mediated suppression of IP levels was not sensitive to pertussis toxin; cholera toxin blocked both TRH stimulation and DA suppression of IP accumulation in response to 100 nM TRH. Neither dibutyryl cAMP nor forskolin lowered IP formation in response to TRH. Phorbol ester decreased TRH-stimulated IP accumulation in D<sub>5</sub>GH<sub>4</sub>C<sub>1</sub> cells; however, an inhibitor of protein kinase C (PKC) did not block the effect of DA.
Effect of Direct Application of Estrogen Aimed at Lateral Septum or Dorsal Raphe Nucleus on Lordosis Behavior: Regional and Sexual Differences in Rats
Authors: Satou Motoyasu , Yamanouchi Korehito 
Published: April 2003

The role of estrogen in lordosis-inhibiting systems in the lateral septum or the dorsal raphe nucleus was investigated in female and male rats. Ovariectomized rats received implantation of 22-gauge guide cannulae to the bilateral or right side of the lateral septum (LS and rLS, respectively), the dorsal raphe nucleus (DRN) or bilateral cortex (CX). In castrated male rats, bilateral implantations of the cannulae to the LS were carried out (mLS). Three behavioral tests in total were performed at 2-week intervals. In the first test, all animals were subcutaneously injected with 1.5 µg/kg estradiol benzoate (EB). Forty-four hours after EB, 0.5 mg progesterone (P) was injected and a behavioral test was started 4 h after P. These hormonal regimes were used in all tests. In the second test, 2 h before EB injection, 27-gauge cannulae filled with estradiol (E<sub>2</sub>) were inserted into the DRN, LS or CX through the guide cannulae and were kept there for 4 h. In the third test, cholesterol was implanted instead of E<sub>2</sub> into these areas. In the first test, most females showed low levels of lordosis quotient (LQ) and most males showed no lordosis. In the second test, mean LQs in the LS or rLS groups of females increased but not in the DRN and CX groups. In the mLS group no increase of LQ was observed. When cholesterol was implanted in the third test, mean LQs in all groups were as low as in the first test. These results suggest the possibility that estrogen releases the inhibition when it acts on the LS, but not on the DRN female rats. On the other hand, inhibition in the male LS may not be released by the direct action of estrogen.
Effects of Chronic ‘Binge’ Cocaine Administration on Plasma ACTH and Corticosterone Levels in Mice Deficient in DARPP-32
Authors: Zhou Yan , Schlussman Stefan D. , Ho Ann , Spangler Rudolph , Fienberg Allen A. , Greengard Paul , Kreek Mary Jeanne 
Published: April 2003

The product of the DARPP-32 gene mediates intracellular signals initiated by the binding of dopamine to its receptors. Cocaine administration leads to increased activation of dopamine receptors, and causes activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis. We determined the effects of chronic ‘binge’ pattern cocaine on HPA activity in mice containing a targeted disruption of the DARPP-32 gene. Mice received three daily injections of cocaine (15 mg/kg/injection) for 14 days, and were sacrificed 30 min after the last injection. We measured the levels of plasma adrenocorticotropin (ACTH) and corticosterone which reflect HPA activity. In wild-type controls, ‘binge’ cocaine administration significantly increased plasma ACTH and corticosterone levels. In contrast, DARPP-32-deficient mice failed to show a significant elevation of either plasma ACTH or corticosterone levels following ‘binge’ cocaine. The results indicate that DARPP-32 plays a role in mediating the stimulatory effects of cocaine on the HPA axis.
Centrally Administered Murine Leptin Stimulates Plasma Arginine-Vasopressin Secretion and Increases the Level of mRNA Expression in the Supraoptic Nucleus of Conscious Rats
Authors: Yamamoto Shigeki , Morimoto Isao , Kai Keiko , Arao Tadashi , Fujihira Takashi , Morita Emiko , Kannan Hiroshi , Eto Sumiya 
Published: April 2003

The product of the <i>ob</i> gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0–400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.
Connexin 26 Expression and Extensive Gap Junctional Coupling in Cultures of GT1-7 Cells Secreting Gonadotropin-Releasing Hormone
Authors: Hu Limin , Olson Andrew J. , Weiner Richard I. , Goldsmith Paul C. 
Published: April 2003

Gap junctions (GJs) are transmembrane channels that permit rapid intercellular transit of various small molecules including ions, second messengers and metabolites. GJs promote communication and coordinated activity between coupled neurons, and may help facilitate the synchronous release and pulsatile secretion of neurohormones. A previous study using GnRH-secreting GT1-7 cells reported that connexin 26 was the major GJ subunit present, and that about 20% of the cultured cells engaged in GJ coupling as assayed by fluorescence recovery after photobleaching of 5,6-carboxyfluorescein diacetate (MW 460 D). To reassess GJ connectivity with a more permeant probe, we grew GT1-7 cells to 70% confluency on Matrigel-coated glass coverslips and microinjected Neurobiotin<sup>TM</sup> (MW 322 D) into single cells. Dye was allowed to diffuse for 30 min before cultures were fixed, and subsequently immunostained for Neurobiotin with 3,3′-diaminobenzidine HCl and examined by light microscopy. Dye coupling between 2 or more GT1-7 cells was observed after 75% of all microinjections. Connectivity involved the somata and neurites of an average of 6.6 ± 2.0 adjoining cells, but in one instance was seen in a group of 32 GT1-7 neighbors. Western blotting and immunofluorescence staining confirmed that connexin 26 was the predominant GJ subunit expressed by GT1-7 cultures. Our results using Neurobiotin suggest these GJ channels may be smaller than anticipated. In addition, functional GJ connectivity between subconfluent GT1-7 cells is more extensive than previously reported, occurring with higher frequency and coupling significantly greater numbers of cultured cells. Since cAMP, IP3, and Ca<sup>2+</sup> are able to pass through GJs and can elicit secretion of GnRH by GT1 cell cultures, GJs may play an important role in the coordination and synchronization of GnRH release.
An Opioid Pathway in the Hypothalamus of the Turkey That Stimulates Prolactin Secretion
Authors: Youngren Orlan M. , Pitts Gilbert R. , Chaiseha Yupaporn , El Halawani Mohamed E. 
Published: April 2003

Circulating prolactin (PRL) levels increase when dynorphin is infused into the turkey brain. This study tested the hypothesis that centrally infused dynorphin requires an intact vasoactive intestinal peptide (VIP) system in order to stimulate turkey PRL secretion. It also investigated the roles of the dopaminergic and serotonergic systems in dynorphin-induced PRL release. Drugs were infused into the third ventricle of anesthetized laying turkeys via stereotaxically guided cannulae and circulating blood was assayed for changes in PRL levels. When a highly selective ĸ opioid receptor antagonist was given prior to dynorphin injection, the PRL response to dynorphin was almost totally blocked. The coinfusion of either a serotonin (5-HT) or a D<sub>1</sub> dopamine (DA) receptor antagonist with dynorphin prevented the increase in PRL observed in birds when dynorphin was infused alone. On the other hand, the ĸ opioid receptor antagonist failed to prevent the 5-HT-induced release of PRL. In hens actively immunized against VIP, infused dynorphin was unable to increase plasma PRL levels and infused VIP gave a muted PRL rise, while large increases in PRL were seen in nonimmunized birds receiving the same infusions. These data show that: (1) dynorphin stimulates PRL secretion by activating ĸ opioid receptors in the avian hypothalamus, and (2) dynorphin, 5-HT, DA, and VIP stimulate avian PRL secretion via a common pathway expressing ĸ opioid, serotonergic, dopaminergic, and VIPergic receptors at synapses arranged serially in that functional order, with the VIPergic system as the final mediator (releasing factor).
Hyperinnervation during Adrenal Regeneration Influences the Rate of Functional Recovery
Authors: Ulrich-Lai Yvonne M. , Engeland William C. 
Published: April 2003

The rat adrenal cortex has the uncommon ability to demonstrate morphological and functional regeneration after injury-induced loss of cortical tissue. Peripheral nerves are involved in tissue regeneration and healing after injury, implying that nerves may also be involved in modulating the regeneration of the adrenal cortex. Studies were initiated to assess changes in adrenal innervation during cortical tissue regeneration subsequent to adrenal enucleation. Innervation of regenerating adrenals was assessed from 3 to 62 days postenucleation by immunohistofluorescent detection of neuronal markers for primary afferent, preganglionic sympathetic, and postganglionic sympathetic fibers. The regenerating adrenal contained few nerves at 3 days postenucleation, but became differentially innervated, with extensive innervation by nerve fibers positive for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), neuropeptide Y (NPY), and neuronal nitric oxide synthase (nNOS). In contrast, there was only minimal innervation by nerve fibers positive for vasoactive intestinal peptide. By 14 days postenucleation, the CGRP-, TH-, and NPY-positive innervation included areas of hyperinnervation in the capsule, cortex, and central inflammatory site of the regenerating gland. In addition, many chromaffin cells were present at all time points postenucleation. Quantification of the regenerating gland content of CGRP, norepinephrine, epinephrine, and nNOS verified the immunohistofluorescent observations. The period of extensive innervation correlated temporally with the time (3–30 days) during which the regenerating glands recovered steroidogenic function. Moreover, splanchnic nerve transection at the time of adrenal enucleation decreased the innervation by CGRP-positive and vesicular acetylcholine transporter-positive fibers and delayed regeneration. These results support the hypothesis that adrenal innervation modulates tissue regeneration and functional recovery of the enucleated adrenal gland.