Biomedical subjects

Andrea De Laurentiis

Publications and source records attributed to Andrea De Laurentiis.

10 recordsLinked to original sources

PubMed2006

Role of ammonia and nitric oxide in the decrease in plasma prolactin levels in prehepatic portal hypertensive male rats.

OBJECTIVES: Since very little is known about neuroendocrine changes that occur in portal-systemic hepatic encephalopathy, we studied plasma prolactin (PRL) levels and the involvement of hyperammonemia, nitric oxide (NO) and dopaminergic and adrenergic systems in the control of this hormone secretion in a male rat model of prehepatic portal hypertension (PH). METHODS: We conducted in vivo studies to determine plasma ammonia and PRL levels. Dopamine (DA), dihydroxyphenylacetic acid (DOPAC), epinephrine and norepinephrine content in medial basal hypothalamus (MBH) and anterior pituitary (AP) were measured. In addition, NO synthase (NOS) activity and protein expression were evaluated in APs. In in vitro studies, the APs from intact rats were incubated with different doses of ammonia and PRL secretion was determined. In ex vivo studies, the APs from normal and PH rats were incubated in the presence of ammonia and/or a NOS inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME) and PRL secretion was determined. RESULTS: PH rats had a significant increase in plasma ammonia levels (p < 0.001) and a decrease in plasma PRL levels (p < 0.05). Neither DA nor DOPAC content or DOPAC/DA ratios were modified in both MBH and APs; however, we observed a significant increase in norepinephrine content in both MBH and AP (p < 0.001 and p < 0.05, respectively) and a significant increase in epinephrine in APs (p < 0.001). Moreover, PH produced an increase in NOS activity (p < 0.01) and NOS protein expression (p < 0.0001) in APs. The ammonia (100 microM) significantly reduced PRL secretion from APs in vitro (p < 0.05). The presence of L-NAME, an inhibitor of NOS, abrogated the inhibitory effect of ammonia on PRL secretion from APs from control and PH rats. CONCLUSIONS: We found that plasma PRL levels were decreased in PH rats probably due to the high ammonia levels. The central noradrenergic system could also mediate this decrease. Also, the increase in NOS activity and/or content in AP induced NO production that directly inhibited PRL secretion from the AP, without the participation of the dopaminergic system.

Ammonia↗

PubMed2006

Decrease in salivary secretion by radiation mediated by nitric oxide and prostaglandins.

OBJECTIVE: In the present work, we evaluated the effect of exposing the submandibular glands (SMG) to radiation, studying different functional parameters such as salivary secretion, nitric oxide (NO) production, reactive oxygen species formation, prostaglandin (PGE) content and apoptosis. METHODS: We irradiated rats in the head and neck region with a single dose of gamma-ray radiation of 15 Gy. Two hours after radiation, we measured norepinephrine-induced salivary secretion. After that, the SMG were dissected, and in this tissue, we measured the activity of NO synthase (NOS), the PGE content, the amount of reactive oxygen species, apoptotic cells and mitochondrial inducible NOS (iNOS) expression. RESULTS: We found that radiation decreased salivary secretion when 10 and 30 microg/kg of norepinephrine was administered via the right femoral vein. We observed that iNOS activity was reduced and PGE content increased after radiation in SMG, indicating that NO and PGEs may participate in salivary secretion. The expression of mitochondrial NOS was increased after radiation leading to the formation of large amounts of NO that acts as a proapoptotic signal. In fact, we observed an augmentation in apoptotic cells. In this study, we also observed an increase in lipid peroxidation induced by radiation that may contribute to tissue damage. CONCLUSIONS: Our results indicate that radiation induced a decrease in salivary secretion and SMG iNOS activity, meanwhile the PGE content, the lipid peroxidation and apoptosis increased in the tissue. These modifications decrease salivary secretion.

Animals↗

PubMed2006

Chronology of advances in neuroendocrine immunomodulation.

This review documents the remarkable progress over the last 50 years of our knowledge of the control of anterior pituitary hormone release and synthesis by a family of peptidic releasing and inhibiting hormones, synthesized in hypothalamic neurons and released into the hypophysial portal vessels. These vessels transport them to the anterior pituitary, where they stimulate release and synthesis of pituitary hormones or inhibit these processes. In general, there are at least two hypothalamic hormones for each pituitary hormone-vasopressin and corticotrophin-releasing hormone (CRH) for adrenocorticotropin hormone (ACTH) and growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GIH) for growth hormone (GH). Some of these hormones have extrapituitary action: for example, luteinizing hormone-releasing hormone (LHRH) stimulates mating behavior. High doses of LHRH have an inhibitory action on the growth of prostate cancer. Proinflammatory and anti-inflammatory cytokines act not only in the brain, but also on the pituitary and peripheral tissues. All of these transmitters are controlled by neuronal transmitters. We anticipate further rapid progress and clinical application of these transmitters and the discovery of new ones.

Animals↗

PubMed2005

The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E2.

The adrenal cortex is a major stress organ in mammals that reacts rapidly to a multitude of external and internal stressors. Adrenocorticotropin (ACTH) is the main stimulator of the adrenal cortex, activating corticosteroid synthesis and secretion. We evaluated the mechanism of action of ACTH on adrenals of male rats, preserving the architecture of the gland in vitro. We demonstrated that both sodium nitroprusside (NP), a nitric oxide (NO) donor, and ACTH stimulate corticosterone release. NO mediated the acute response to ACTH because Nomega-nitro-l-arginine methyl ester, a NO synthase inhibitor, and hemoglobin, a NO scavenger, blocked the stimulation of corticosterone release induced by ACTH. NP stimulated prostaglandin E release, which in turn stimulated corticosterone release from the adrenal. Additionally, indomethacin, which inhibits cyclooxygenase, and thereby, prostaglandin release, prevented corticosterone release from the adrenal induced by both NP and ACTH, demonstrating that prostaglandins mediate acute corticosterone release. Corticosterone content in adrenals after incubation with ACTH or NP was lower than in control glands, indicating that any de novo synthesis of corticosterone during this period was not sufficient to keep up with the release of the stored hormone. The release induced by ACTH or NP depleted the corticosterone content in the adrenal by approximately 40% compared with the content of glands incubated in buffer. The mechanism of rapid release is as follows: NO produced by NO synthase activation by ACTH activates cyclooxygenase, which generates PGE(2), which in turn releases corticosterone stored in microvesicles and other organelles.

Adrenal Cortex↗

PubMed2004

The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen.

Because Delta-9-tetrahydrocannabinol (THC) inhibited luteinizing hormone-releasing hormone (LHRH) in male rats, we hypothesized that the endocannabinoid, anandamide (AEA), would act similarly. AEA microinjected intracerebroventricularly (i.c.v.) decreased plasma luteinizing hormone (LH) at 30 min in comparison to values in controls (P < 0.001). The cannabinoid receptor 1 (CB1-r)-specific antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (10(-9) M) decreased LHRH release from medial basal hypothalami incubated in vitro. These results support the concept that endogenous AEA inhibits LHRH followed by decreased LH release in male rats. In ovariectomized (OVX) female rats, AEA i.c.v. also inhibited LH release, but in this case AM251 had an even greater inhibitory effect than AEA. In vitro, AEA had no effect on LHRH in OVX rats. It seems that endogenous AEA inhibits LHRH followed by decreased LH release in OVX rats but that AM251 has an inhibitory action in this case. In striking contrast, in OVX, estrogen-primed (OVX-E) rats, AEA i.c.v. instead of decreasing LH, increased its release. This effect was completely blocked by previous injection of AM251. When medial basal hypothalami of OVX-E rats were incubated, AEA increased LHRH release. The synthesized AEA was higher in OVX-E rats than in OVX and males, indicating that estrogen modifies endocannabinoid levels and effects. The results are interpreted to mean that sex steroids have profound effects to modify the response to AEA. It inhibits LHRH and consequently diminishes LH release in males and OVX females, but stimulates LHRH followed by increased LH release in OVX-E-primed rats.

Animals↗

PubMed2004

Alcohol inhibits luteinizing hormone-releasing hormone release by activating the endocannabinoid system.

We hypothesized that ethanol (EtOH) might act through the endocannabinoid system to inhibit luteinizing hormone-releasing hormone (LHRH) release. Therefore, we examined the mechanism by which EtOH and anandamide (AEA), an endogenous cannabinoid, inhibit LHRH release from incubated medial basal hypothalamic explants. In previous work, we demonstrated that EtOH inhibits the N-methyl-D-aspartic acid-stimulated release of LHRH by increasing the release of two neurotransmitters: beta-endorphin and gamma-aminobutyric acid (GABA). In the present work, bicuculline, a GABAergic antagonist, completely prevented the inhibition of AEA (10(-9)M) on N-methyl-D-aspartic acid-induced LHRH release, but naltrexone, a micro-opioid receptor antagonist, had no effect. AEA also significantly increased GABA release but had no effect on beta-endorphin release. Therefore, AEA could inhibit LHRH release by increasing GABA but not beta-endorphin release. Because EtOH and AEA acted similarly to inhibit LHRH release, we investigated whether both substances would affect the adenylate cyclase activity acting through the same GTP-coupled receptors, the cannabinoid receptors 1 (CB1-rs). AEA and EtOH (10(-1)M) reduced the forskolin-stimulated accumulation of cAMP, but AM251, a specific antagonist of CB1-r, significantly blocked that inhibition. Additionally we investigated whether CB1-r is involved in the inhibition of LHRH by EtOH and AEA. AEA and EtOH reduced forskolin-stimulated LHRH release, but AM251 significantly blocked that inhibition. Also, we demonstrated that EtOH did not act by increasing AEA synthase activity to inhibit LHRH release in our experimental conditions. Therefore, our results indicate that EtOH inhibits the release of LHRH acting through the endocannabinoid system.

Animals↗

PubMed2003

Characterization of tachykinin NK2 receptor in the anterior pituitary gland.

Tachykinins are a family of bioactive peptides that interact with three subtypes of receptors: NK1, NK2 and NK3. Substance P has greater affinity for NK1, and neurokinin A (NKA) for NK2 receptor subtype. Although only NK1 receptor has been characterized in the anterior pituitary gland, some evidence suggests the existence of NK2 receptors in this gland. Therefore, we investigated the presence of NK2 receptors in the anterior pituitary gland of male rats by radioligand binding studies using labeled SR48968, a non peptidic specific antagonist. [3H]SR48968 specific binding to cultured anterior pituitary cells was time-dependent and saturable, but with a lower affinity than previously reported values for cells expressing NK2 receptors. Unlabeled NKA inhibited only partially [(3)H]SR48968 specific binding to whole anterior pituitary cells. Since SR48968 is a non polar molecule, we performed experiments to discriminate surface from intracellular binding sites. SR48968 exhibited both surface and intracellular specific binding. Analysis of the surface-bound ligand indicated that [3H]SR48968 binds to one class of receptor with high affinity. Neurokinin A completely displaced [3H]SR48968 surface specific binding fitting to a two-site/two-state model with high and low affinity. Additionally, immunocytochemical studies showed that the NK2 receptor is expressed at least in a subset of lactotropes. These results demonstrate the presence of NK2 receptors in the anterior pituitary gland and suggest that NKA actions in this gland are mediated, at least in part, by the NK2 receptor subtype.

Animals↗

PubMed2003

Effects of lipopolysaccharide on neurokinin A content and release in the hypothalamic-pituitary axis.

The administration of bacterial lipopolysaccharide (LPS) markedly affects pituitary secretion, and its effects are probably mediated by cytokines produced by immune cells or by the hypothalamo-pituitary axis itself. Since neurokinin A (NKA) plays a role in inflammatory responses and is involved in the control of prolactin secretion, we examined the in vivo effect of LPS on the concentration of NKA in hypothalamus and pituitary (assessed by RIA) and serum prolactin levels in male rats. One hour after the intraperitoneal administration of LPS (250 microg/rat), NKA content was decreased in the posterior pituitary but not in the hypothalamus or anterior pituitary. Three hours after injection, LPS decreased NKA concentration in the hypothalamus and anterior and posterior pituitary. In all the conditions tested, LPS significantly decreased serum prolactin. We also examined the in vitro effects of LPS (10 microg/ml), interleukin-6 (IL-6, 10 ng/ml) and tumor necrosis factor alpha (TNF-alpha, 50 ng/ml) on hypothalamic NKA release. Interleukin-6 increased NKA release without modifying hypothalamic NKA concentration, whereas neither LPS nor TNF-alpha affected them. Our results suggest that IL-6 may be involved in the increase of hypothalamic NKA release induced by LPS. NKA could participate in neuroendocrine responses to endotoxin challenge.

Animals↗

PubMed2003

The effect of anandamide on prolactin secretion is modulated by estrogen.

Recent research has revealed that endogenous cannabinoid receptors (CB1 and CB2) react with the active ingredient of marijuana, Delta(9)-tetrahydrocannabinol. Two endogenous ligands activate these receptors. The principal one, anandamide (AEA), activates CB1. AEA and CB1 are localized to various neurons within the brain. Because Delta(9)-tetrahydrocannabinol inhibited prolactin (Prl) secretion following its intraventricular injection into male rats, we hypothesized that AEA would have a similar effect. Estrogen modifies many hormonal responses and is known to increase Prl secretion. Therefore, we hypothesized that responses to intraventricular AEA would change depending on the gonadal steroid environment. Consequently, we evaluated the effects of lateral cerebral ventricular microinjection of AEA (20 ng) into male, ovariectomized (OVX), and estrogen-primed (OVX-E) rats. AEA decreased plasma Prl in male rats, had little effect in OVX females, and increased Prl in OVX-E rats. The results were at least partially mediated by changes in dopaminergic turnover, altering the inhibitory dopaminergic control of Prl release by the anterior pituitary gland. Thus, dopamine turnover was increased in the male rats and decreased significantly in OVX and in OVX-E rats. The changes in Prl may be caused not only by altered dopamine input to the anterior pituitary gland but also by effects of AEA on other transmitters known to alter Prl release. Importantly, in OVX-E rats, the elevated Prl release and the response to AEA were blocked by the AEA antagonist, indicating that AEA is a synaptic transmitter released from neurons that decrease inhibitory control of Prl release.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Lipopolysaccharide- and tumor necrosis factor-alpha-induced changes in prolactin secretion and dopaminergic activity in the hypothalamic-pituitary axis.

Bacterial lipopolysaccharide (LPS) affects pituitary hormone secretion, including prolactin release, by inducing synthesis and release of cytokines such as tumor necrosis factor-alpha (TNF-alpha). Since prolactin is mainly under tonic inhibitory control of dopamine, we investigated the effect of LPS and TNF-alpha on the hypothalamic-pituitary dopaminergic system. LPS (100-250 microg/rat, i.p.) decreased serum prolactin levels after 1 or 3 h. Sulpiride, a dopaminergic antagonist, increased serum prolactin and blocked the inhibitory effect of LPS. LPS increased hypothalamic dopamine and DOPAC concentrations and the DOPAC/dopamine ratio both in mediobasal hypothalamus and the posterior pituitary. LPS also enhanced dopamine and DOPAC concentration in the anterior pituitary. LPS elevated plasma levels of epinephrine, norepinephrine and dopamine but it did not modify the concentration of epinephrine or norepinephrine in the tissues studied. The administration of TNF-alpha (i.c.v., 1 h, 100 ng/rat) decreased serum prolactin but did not affect plasma catecholamine levels. TNF-alpha did not modify the DOPAC/dopamine ratio in hypothalamus or posterior pituitary but increased dopamine and DOPAC concentrations in the anterior pituitary. Incubations of hypothalamic explants showed that TNF-alpha did not modify in vitro basal dopamine release and reduced K(+)-evoked dopamine release. On the contrary, incubations of posterior pituitaries showed that TNF-alpha significantly increased basal and K(+)-evoked dopamine release. These results indicate that LPS and TNF-alpha increase dopamine turnover in the hypothalamic-pituitary axis. This increase in dopaminergic activity could mediate the inhibitory effect of LPS and TNF-alpha on prolactin release. Furthermore, the increase in dopaminergic activity elicited by LPS could be mediated by an increase in hypothalamic TNF-alpha during endotoxemia.

3,4-Dihydroxyphenylacetic Acid↗