Effects of long-term antiepileptic therapy on the hypothalamic-pituitary axis in man

Effects of long-term antiepileptic therapy on the hypothalamic-pituitary axis were evaluated from the basal and stimulated plasma levels of growth hormone (GH) and prolactin (PRL) and from circadian adrenocorticotropic hormone (ACTH)/cortisol rhythms. Data for patients with well-controlled epilepsy of mild-to-moderate severity were compared with those for normal healthy volunteers. Analysis of the effects of each antiepileptic drug (AED) and of combined AEDs revealed minor abnormalities of stimulated GH secretion in all treated patients. In epileptic men, all individual AEDs (except valproate) and AED polytherapy increased both basal and stimulated plasma levels of PRL. In epileptic women, this effect was more variable and less marked, probably because of early depletion of PRL reserves. Each AED and combined AEDs did not significantly change circadian ACTH/cortisol rhythms in epileptic patients. The effects observed seem not to be related to epilepsy per se. Clinical implications, pathways, and neurotransmitters involved and possible mechanisms of the neuroendocrine effects of long-term AED therapy are discussed.     

Novel hypothalamic and preoptic sites of prepro-melanin-concentrating hormone messenger ribonucleic Acid and Peptide expression in lactating rats

The deduced structure of the rat melanin-concentrating hormone (MCH) precursor predicted the existence of at least two peptides that may be processed from it, one similar to teleost MCH and a second novel neuropeptide, NEI. Cellular localization studies confirmed that prepro-MCH (ppMCH) mRNA and the MCH and NEI peptides are expressed predominantly in cells in the zona incerta and caudal lateral hypothalamic area with minor contingents seen in the olfactory tubercle and pons. A moderate MCH-and NEI-immunoreactive axonal projection to the median eminence and, particularly, to oxytocin-rich regions of the posterior pituitary suggested some anatomical heterogeneity of ppMCH-expressing neurons in the hypothalamus, and an involvement in neuroendocrine function. In the present study, immunohistochemical and hybridization histochemical methods were used to follow MCH gene and peptide expression as a function of reproductive status in female rats. Nursing dams sacrificed after 8 to 21 days of lactation consistently displayed ppMCH mRNA and MCH and NEI immunoreactivity in a discrete and contiguous band, encompassing the ventral aspect of the medial part of the medial preoptic nucleus, the periventricular preoptic nucleus, and the most rostral aspects of the paraventricular nucleus of the hypothalamus (PVH). Combined immunohistochemical (for oxytocin) and hybridization histochemical (for ppMCH mRNA) staining failed to reveal a significant degree of congruence in the two chemically-specified cell populations in the PVH of lactating dams. The apparent induction of ppMCH-derived peptides and mRNA in the preoptic area and PVH was not apparent in animals sacrificed 4 to 8 days after weaning, during late pregnancy, or at any point in the estrous cycle. Moreover, no frank alterations in ppMCH mRNA were evident in the principal sites at which ppMCH is expressed at constitutively high levels, i.e. in the lateral hypothalamic area and zona incerta, as a function of reproductive status. The loci and apparent state-dependency of the induction of ppMCH mRNA and peptide expression suggests a role for these gene products in the control of lactation.     

Parental divorce and neuroendocrine changes in adolescents

Plasma noradrenaline (NE), adrenocorticotrophic hormone (ACTH), growth hormone (GH), prolactin (PRL) and luteinizing hormone (LH) concentrations were examined in basal conditions and after stimulation by the step test in two groups of psychophysically healthy adolescent girls, 18 from divorced families and 16 from non-divorced families. Basal NE, ACTH, GH, PRL values did not differ in the two groups, whereas those of LH were significantly lower in the adolescents from divorced parents than in those from non-divorced families. Responses of NE and ACTH to the stimulus were normal, of GH and PRL were weaker, and of LH slightly weaker in children of divorced parents. An impaired catecholaminergic and serotoninergic tonus in children of disrupted families might underly the hormonal alterations.     

Study of the origins of melanin-concentrating hormone and neuropeptide EI immunoreactive projections to the periaqueductal gray matter

Previous studies have described the distribution of melanin-concentrating hormone (MCH) and neuropeptide EI (NEI) in the rat central nervous system (CNS), and revealed this peptidergic system to be primarily localized in neurons within the lateral hypothalamic area (LHA) and zona incerta (ZI). Moreover, an extensive MCH- and NEI-immunoreactive (ir) fiber distribution has been described throughout the CNS, including a dense innervation within the periaqueductal gray matter (PAG). MCH and NEI have become important markers for the LHA, which harbors a variety of neuronal types as well as the medial forebrain bundle, a complex system of fibers which extends rostrocaudally throughout this area. In the present study, the projection patterns of MCH- and NEI-ir fibers within the PAG were characterized using a diamino benzidine immunoperoxidase procedure to localize each of these peptides in normal rat brain sections. MCH- and NEI-ir fibers were seen coursing through all of its subdivisions the entire length of the PAG, with a more condensed number of fibers in the periaqueductal medial zone. The primary origin(s) of these PAG afferents were determined in combined retrograde tracing immunofluorescent studies in which true blue (TB) was injected into various subdivisions of the PAG. TB-filled MCH-ir neurons were identified mainly in the rostral portion of the medial ZI (ZIm) and in the tuberal LHA (LHAt). Studies confirming this MCH-ir projection in which anterograde tracer (Phaseolus vulgaris leucoagglutinin) was injected into various regions in and around the LHA and ZI revealed a distinction in the PAG projections arising from these nuclei. ZIm injections resulted in labeled fibers mainly within the rostral dorsomedial and dorsolateral regions of the PAG, whereas injections in the LHAt revealed an innervation at intermediate and caudal levels in the ventrolateral region. Since the MCH and NEI fiber distribution patterns in the PAG are identical, this would suggest that these peptides are colocalized within the hypothalamus. Sequential immunofluorescent staining for MCH and NEI on tissue from rats who had received TB injections into the PAG confirmed this, and revealed that approximately 15% of all tracer-filled neurons in the LHA and ZI were both MCH- and NEI-ir. In fact, the vast majority of MCH-ir neurons within these regions also colocalize with NEI. Therefore, the MCH/NEI projection patterns within the PAG arise from two major sources: the ZIm which supplies afferents via a medial pathway that enters the PAG dorsally at rostral levels, and a pathway originating in the LHA that enters the PAG ventrally at more caudal levels. The ZIm and LHA are believed to be the primary, if not the only, sources of MCH and NEI projections to the PAG.     

乙酰胆碱受体抗体抑制烟碱对大鼠下丘脑-垂体-肾上腺轴作用的研究

目的研究乙酰胆碱受体抗体(nAchRab)IgG在烟碱模拟应激状态下对下丘脑-垂体-肾上腺 (HPA)轴各层面活动的影响,探讨重症肌无力(MG)和MG危象发生机制与HPA内分泌轴变化的关系。方法将 nAchRab IgG或正常人IgG注入大鼠侧脑室,继后经烟碱刺激;应用原位杂交、放射免疫和化学发光免疫法观察:实验组和对照组鼠下丘脑、海马和颞叶促肾上腺皮质释放激素(CRH)mRNA表达和血浆促肾上腺皮质激素(ACTH) 及皮质酮(CORT)浓度。结果在基础状态,nAchRab抑制下丘脑CRHmRNA表达,对海马、颞叶CRHmRNA表达无抑制,对血浆ACTH及CORT水平无影响;nAchRab抑制烟碱所诱导的下丘脑、海马及颞叶CRHmRNA表达,血浆 ACTH及CORT水平下降。结论 nAchRab能与下丘脑、海马及颞叶的乙酰胆碱受体(nAchR)结合,基础状态仅抑制下丘脑CRHmRNA表达;在烟碱诱导的状态下则整个HPA功能受抑制,结果模拟了应激状态MG发病和MG危象时的状况,提示MG发病和MG危象发生可能与HPA功能低下有关。     

The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization.

In addition to a nonadecapeptide homologous to the teleost melanin-concentrating hormone (MCH), the amino acid sequence predicted from a rat prepro-MCH (ppMCH) cDNA suggested that at least one (neuropeptide EI, or NEI), and possibly a second (NGE), additional neuropeptide may be encoded by this precursor. Cross-reactivity with epitopes of NEI or NGE can account for reported localization of alpha-MSH, rat CRF, and human GRF in rat dorsolateral hypothalamic neurons. We have used antisera raised against rat MCH and NEI in immunohistochemical studies at the light and electron microscopic levels, along with hybridization histochemical localization of ppMCH mRNA, to define the organization of this system. As expected, ppMCH mRNA is prominently expressed in cells in the lateral hypothalamic area and zona incerta. The MCH and NEI peptides were extensively colocalized in neurons in both of these areas. In addition, smaller cell groups in the olfactory tubercle and pontine tegmentum were also positively hybridized for ppMCH mRNA and immunostained for MCH and NEI. Fibers stained for MCH and NEI were similarly, and very broadly, distributed throughout the central nervous system in patterns that generally conformed with known projection fields of the lateral hypothalamic area and zona incerta. A differential distribution was seen in at least one region, the interanterodorsal nucleus of the thalamus, which contained a prominent terminal field stained for MCH but not NEI. At the electron microscopic level, MCH-stained perikarya displayed a prominent staining associated with the Golgi apparatus; this was not encountered in NEI-stained cells. Both peptides were distributed similarly in terminals in the lateral hypothalamic area and median eminence, with staining associated principally with dense-cored vesicles. The results suggest that ppMCH-derived peptides may serve as neurotransmitters or modulators of prominence in a surprisingly expansive projection field of incerto-hypothalamic neurons. The terminal distributions of this system seem most compatible with functional roles in generalized arousal and sensorimotor integration, processes previously implicated as being subject to modulation by the lateral hypothalamic area.     

Effect of intracerebroventricular injection of nicotinic acetylcholine receptor antibodies on ACTH, corticosterone and prolactin secretion in the male rat

The aim of the present study was to investigate the involvement of CNS nicotinic receptors for acetylcholine in the secretory activity of the hypothalamo-hypophyseal-adrenal axis and prolactin (PRL). Adult male rats received a daily intraventricular injection of partially purified nicotinic acetylcholine receptor antibodies (anti-AChR) obtained from a female patient with myasthenia gravis, for 5 consecutive days. Control animals were treated similarly with immunoglobulins obtained from a healthy woman. Blood samples were withdrawn either under basal conditions or following ether stress. Treatment with anti-AChR increased basal ACTH and corticosterone (CS) levels (by approximately two-fold) but completely inhibited the responses of these hormones and PRL to ether stress. In control animals, normal basal and stress-induced responses of ACTH, CS and PRL were observed.This study demonstrated the importance for nicotinic acetylcholine receptors in the mediation of basal and stress-induced adrenocortical activity as well as for the mediation of PRL secretion in response to stress.     

Diuretic and Natriuretic Actions of Melanin Concentrating Hormone in Conscious Sheep

Melanin concentrating hormone (MCH) is a 19 amino-acid peptide expressed in high concentrations within the dorso-lateral hypothalamus of rats, sheep and man. MCH regulates skin colour and ACTH release in teleost fish, however, its physiological relevance in mammals is unclear. The present study examined the cardiovascular and metabolic actions of intracerebroventricular (i.e.v.) infusion of MCH, and the pro-MCH derived peptide Neuropeptide-E-I (NEI), in conscious, chronically instrumented sheep. Human MCH (1–19) or NEI (1–13) was infused i.e.v. for 24 h into 6 sheep, and measurements were made every 10 min of arterial pressure, heart rate, cardiac output, stroke volume and peripheral blood flow/conductance. Recordings of water intake (H²Oin), urine volume (Uv), urinary Na (UNaV) and K excretion (UKV) were made, as well as hematocrit, plasma Na, K, osmolality, protein, glucose, ACTH, vasopressin, renin, endothelin, ANF, Cortisol and aldosterone concentrations. After 24 h of infusion at 10 μg/h, MCH produced a significant increase in Uv from 0.8 ± 0.2 to 1.4 ± 0.3 l/day, together with an increase in UNaV from 56 ± 8 to 107 ± 14 mmol/day, and in UKV from 202 ± 18 to 369 ± 38 mmol/day. H²Oin was unchanged. Similar renal changes were observed during i.e.v. infusion of NEI. There was no change in any cardiovascular parameter, although hematocrit showed a large decrease with infusion of both peptides after 24 h infusion. Plasma osmolality increased from 291 ±1 to 295 ± 1 mOsm/kg during MCH infusion, whereas total protein and plasma Na and K were unchanged. MCH increased plasma glucose from 3.4 ± 0.2 to 3.8 ± 0.2 mmol/l. Plasma aldosterone exhibited a 30–40% decrease following MCH or NEI infusion, whereas all other plasma concentrations remained unchanged. This study has shown that i.c.v. infusion of MCH or NEI can produce diuretic, natriuretic and kaliuretic changes in conscious sheep, triggered by a possible increase in plasma volume as indicated by the changes in hematocrit. These results, together with anatomical data reporting the presence of MCH/NEI in fluid regulatory areas of the brain, indicate that MCH/NEI may be an important peptide involved in the central control of fluid homeostasis in mammals.     

Melanin-concentrating hormone (MCH) is colocalized with α-melanocyte-stimulating hormone (α-MSH) in the rat but not in the human hypothalamus

Melanin-concentrating hormone (MCH)-containing neurons have recently been localized in the dorsolateral region of the rat hypothalamus, an area where the second α-MSH system is found which contains only α-MSH and none of the pro-opiomelanocortin (POMC)-related peptides. In order to study the morphological relationships between the MCH and α-MSH neuronal systems, we have studied the immunocytochemical localization of both MCH and α-MSH in the rat hypothalamus. The same study was also performed in the human hypothalamus where there is only one α-MSH system which contains α-MSH as well as the other POMC-related peptides (first α-MSH system). In the rat dorsolateral hypothalamus, we could demonstrate that most neuronal cell bodies stained for MCH also contained immunoreactive α-MSH. In the human hypothalamus, neuronal cell bodies stained for MCH were observed only in the periventricular area whereas cell bodies containing α-MSH were exclusively located in the infundibular (arcuate) nucleus. In the rat, immunoelectron microscopy showed labelling for MCH in the dense core vesicles of positive neurons and double-staining techniques clearly demonstrated that both immunoreactive MCH and α-MSH could be consistently detected in the same dense core vesicles. These ultrastructural studies then suggest that these two peptides should be released simultaneously from neurons located in the rat dorsolateral hypothalamus.     

急性脑血管病并／不并多器官功能衰竭患者下丘脑—垂体—肾上腺皮质轴功能研究

应用放射免疫分析法对１６７例急性脑血管病（ＡＣＶＤ）患者血清泌乳素（ＰＲＬ）、生长激素（ＧＨ）、皮质醇（Ｆ）及血浆促肾上腺皮质激素（ＡＣＴＨ）水平变化进行了观察。结果发现：ＡＣＶＤ患者ＰＲＬ、ＧＨ、ＡＣＴＨ与Ｆ水平均显著高于对照组，ＡＣＶＤ并多器官功能衰竭（ＭＤＦ）患者４种激素水平显著高于ＡＣＶＤ各疾病组，随ＡＣＶＤ病程不同，４种激素水平也相应改变，１周时水平最高，２周后逐渐恢复、ＡＣＶＤ并ＭＤＦ重型患者（ＭＤＦ积分＞４分）ＰＲＬ、ＧＨ与Ｆ水平显著高于轻型患者（ＭＤＦ积分≤４分）。结果提示ＰＲＬ、ＧＨ和Ｆ可能参与了ＡＣＶＤ并ＭＤＦ的病理生理过程。     

Endocrinological effects of mirtazapine in healthy volunteers

Objective: Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin (5-HT) but acts as an antagonist at presynaptic ₂-receptors and at postsynaptic 5-HT₂, 5-HT₃ and histamine H₁-receptors. In the present investigation, the influence of acute oral administration of 15-mg mirtazapine on the cortisol (COR), adrenocorticotropin (ACTH), growth hormone (GH) and prolactin (PRL) secretion was examined in 12 healthy male subjects, compared to placebo. Methods: After insertion of an intravenous catheter, both the mean arterial blood pressure (MAP) and the heart rate were recorded and blood samples were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.), at time of administration (8:00 a.m.) and during 5 h thereafter in periods of 30 min. Concentrations of COR, ACTH, GH and PRL were measured in each blood sample by double antibody radioimmunoassay and chemiluminescence immunoassay methods. The area under the curve (AUC; 0–300 min after mirtazapine or placebo administration) was used as parameter for the COR, ACTH, GH and PRL response. Furthermore, the urinary free cortisol excretion (UFC) was determined beginning at 8:00 a.m. (time of administration of placebo or mirtazapine) up to 8:00 a.m. the day after. Results: Two-sided t-tests for paired samples revealed significantly lower COR AUC, ACTH AUC, UFC and PRL AUC values after 15-mg mirtazapine compared to placebo, whereas no significant differences were found with respect to GH AUC, MAP and heart rate. Conclusions: Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (e.g., inhibition of hypothalamic corticotropin releasing hormone (CRH) output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH₁ receptor antagonists.     

Endocrine effects of centrally injected nociceptin in the rat

In the present study we investigated the mechanisms involved in the endocrine effect of nociceptin/orphanin FQ (OFQ) in the rat and the possible interaction between OFQ and morphine in the control of growth hormone (GH) secretion. The intracerebroventricular administration of OFQ (2.3 or 23 microg/rat, i.c.v.) in freely moving male rats caused an increase in the secretion of both GH and prolactin (PRL). The possible involvement of the catecholaminergic (CA) system was studied by administering OFQ to CA-depleted rats (rats given 200 mg/kg of alpha-methyl-p-tyrosine subcutaneously 2 h before the i.c.v. dose of OFQ). In these CA-depleted rats, administration of OFQ (23 microg/rat, i.c.v.) did not stimulate GH secretion, whereas it significantly enhanced PRL secretion. In rats anesthetized with ketamine, which induces a significant increase of GH, PRL and corticosterone secretion by activating the sympathetic tone, OFQ (23 microg/rat, i.c.v.) did not modify GH and corticosterone levels, whereas again it significantly potentiated PRL secretion. Overall these results indicate that CA system is involved in the stimulatory action of OFQ on GH but not on PRL secretion. In fact the stimulation of PRL, but not that of GH, was still evident after impairment of the CA system. Pretreatment with OFQ (23 microg/rat, i.c.v.) attenuated the GH secretion induced by morphine (1 mg/kg, given by intra-arterial injection), thus showing a negative interaction between OFQ and morphine in the control of GH secretion.     

Changes in anterior pituitary hormone secretion and hypothalamic catecholamine metabolism during morphine withdrawal in the female rat

Studies were undertaken to evaluate the acute responses of hypothalamic noradrenergic and dopaminergic neurons and anterior pituitary hormones to naloxone (NAL)-precipitated morphine (MOR) withdrawal in the rat. Ovariectomized female rats were rendered MOR-dependent and injected with NAL (1 mg/kg b.w., s.c.). During precipitated MOR withdrawal, a decline in norepinephrine (NE) concentrations was preceded by an increase in the level of its metabolite normetanephrine (NME) in the medial basal hypothalamus (MBH) as well as the preoptic area-anterior hypothalamus (POA-AH). Both dopamine (DA) and its major acid metabolite, dihydroxyphenylacetic acid (DOPAC), showed increased concentrations in these two hypothalamic regions within 30 min of NAL administration. Elevated luteinizing hormone (LH) and beta-endorphin secretion was evident within 5 min of NAL injection to MOR-dependent rats, while serum prolactin (PRL) increased 15 min into MOR withdrawal. Both growth hormone (GH) and thyroid-stimulating hormone (TSH) were depressed over the course of MOR withdrawal. Although a cause and effect relationship cannot be established, during NAL-precipitated MOR withdrawal, a heightened hypothalamic monoaminergic neuronal activity is accompanied by a differential response of anterior pituitary hormones. The observed responses, which are similar to those seen during acute stress, indicate that MOR withdrawal may activate the same mechanisms which mediate the neuroendocrine response to stress.     

Endorphin-related peptides in rat cerebrospinal fluid

Cerebrospinal fluid (CSF) samples were taken from rats implanted with chronic cisternal cannulae and assayed for methionine-enkephalin, beta-endorphin and corticotropin (ACTH). Immobilization stress had little apparent effect on immunoreactive levels of the peptides in the CSF. Gel chromatographic analysis of the beta-endorphin- and ACTH-immunoreactive profiles in rat CSF revealed several peaks. beta-Endorphin-immunoreactive peaks were present at the expected positions of pro-opiocortin, beta-lipotropin and beta-endorphin. ACTH-immunoreactive peaks eluted at positions corresponding to pro-opiocortin, the 20-23K ACTH biosynthetic intermediate, 14K ACTH, and 4.5K ACTH. These results suggest that rat CSF contains peptides of the pro-opiocortin family similar to those previously described in rat pituitary.     

Neuroendocrine responses to psychological stress in adolescents with anxiety disorder

Neurotransmitter-neuroendocrine and cardiovascular responses to the administration of a psychologically stressful mixed-model test (Mental Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were examined in 20 male peripubertal subjects affected by anxiety disorder (group A: 14 with generalized anxiety disorder, 6 with generalized anxiety disorder and separation anxiety disorder) and 20 junior school adolescents, matched for age, without overt psychological disorders (group B). Plasma levels of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te) were measured immediately before the beginning of the tests and 30 min later at their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly higher in anxious subjects than in controls. There was no difference in NE, EPI, CORT and Te prestress levels in the two groups. After the psychological stress session NE, GH and Te concentrations increased significantly in anxious subjects (A), but not in controls. In contrast, beta-EP and PRL decreased significantly during the psychological stress session in anxious subjects, and were unaffected by stress in the subjects without anxiety. No significant changes were found in ACTH, CORT and EPI during the challenge either in anxious subjects or in controls, which may be attributed to the late time of poststress blood sampling. In contrast to controls, heart rate and systolic blood pressure increased significantly in anxious subjects after psychological stress testing. Our data support the hypothesis that the hyperactivity of the noradrenergic system in response to stress is associated with anxiety disorders in adolescents and might influence the responses of GH and Te. High prestress basal values of stress hormones seem to be induced in anxious subjects by the anticipation of the task or by a persistent hyperactivity of the noradrenergic system. Further studies are needed to investigate in more detail the involvement of the HPA axis in anxious adolescents by a more refined resolution of time points of blood sampling.     

Regulation of corticotropin-releasing hormone receptors and hypothalamic pituitary adrenal axis responsiveness during cold stress

The relationship between pituitary corticotropin-releasing hormone (CRH) receptor changes and corticotrope responsiveness was studied during chronic cold stress. Exposure of rats to 4°C caused a gradual increase in plasma adrenocorticotropic hormone (ACTH), reaching 3-fold over the basal levels by 6 h (P< 0.005), followed by a reduction to levels only 1.3-fold over basal by 60 h. Plasma corticosterone was significantly increased after 1 h (P<0.005) and remained elevated for up to the 60 h cold exposure (P < 0.005). No significant changes in plasma thyroid-stimulating hormone, prolactin, growth hormone or vasopressin were observed at 60 h of cold exposure. CRH receptor concentration in the anterior pituitary was unchanged after 18 or 60 h cold stress, whereas in neurointermediate lobe membranes was markedly elevated. Autoradiographic analysis of pituitary CRH receptors confirmed that the increase in CRH binding was confined to the intermediate pituitary. CRH receptor levels in membranes from two brain areas, frontal cortex and amygdala, were unchanged following 60 h cold stress. The areas under the curve for the plasma ACTH and corticosterone levels following an injection of 10μg/kg ovine CRH in conscious rats, were of similar magnitude in control and 60 h cold exposed rats. Plasma ACTH responses to ether stress were significantly higher in rats exposed to cold for 60 h than in controls. In the intermediate pituitary, basal ß-endorphin/lipotropin release from isolated intermediate pituitary cells was significantly lower in cold stressed rats, and despite the increase in CRH receptors CRH-stimulated values were not higher than in controls. Following 60 h cold exposure, immunoreactive CRH content was decreased in neurointermediate pituitary extracts, while it was slightly increased in the median eminence. Exposure to ether for 5 min resulted in a significant decrease in immunoreactive CRH in the median eminence of cold stressed rats, but not in the controls. The data show a lack of correlation between changes in CRH receptor levels and responsiveness of the corticotrope in the anterior and intermediate pituitary lobes. This suggests that postreceptor events and interaction of CRH with other regulators of ACTH secretion are more likely to account for the changes in pituitary responsiveness during chronic stress.     

Monosodium glutamate: Acute and chronic effects on rhythmic growth hormone and prolactin secretion, and somatostatin in the undisturbed male rat

The present investigation was designed to determine the chronic effects of neonatal monosodium glutamate (MSG) administration (4 g/kg s.c.) and the acute effects of MSG (1 g/kg i.p.) on episodic growth hormone (GH) and prolactin (PRL) secretion and brain somatostatin (SRIF) in unanesthetized, chronically cannulated male rats.Adult rats showed the typical physical characteristics that result from neonatal MSG administration. Analysis of episodic GH secretion showed a significant reduction in: (1) the amplitude of GH secretory peaks; and (2) the mean 5.5-h plasma level of GH. Bursts of plasma PRL were inhibited by MSG, but the mean 5.5-h plasma levels were not affected. SRIF concentrations in the medial basal hypothalamus were reduced by 60% after neonatal MSG. Acute administration of MSG to adult rats caused an immediate, long-lasting suppression of rhythmic GH secretion and a rapid, transient release of PRL.These results suggest: (1) neonatally administered MSG causes a marked disturbance in episodic GH and PRL secretion in adult rats; (2) MSG induces a decrease in hypothalamic SRIF and possibly GH-releasing factor; and (3) the acute effects of MSG on GH and PRL may be due to the inhibition and/or excitation of a complex neuronal network involving monoaminergic and peptidergic systems.     

Melanin-concentrating hormone (MCH) is colocalized with alpha-melanocyte-stimulating hormone (alpha-MSH) in the rat but not in the human hypothalamus

Melanin-concentrating hormone (MCH)-containing neurons have recently been localized in the dorsolateral region of the rat hypothalamus, an area where the second alpha-MSH system is found which contains only alpha-MSH and none of the pro-opiomelanocortin (POMC)-related peptides. In order to study the morphological relationships between the MCH and alpha-MSH neuronal systems, we have studied the immunocytochemical localization of both MCH and alpha-MSH in the rat hypothalamus. The same study was also performed in the human hypothalamus where there is only one alpha-MSH system which contains alpha-MSH as well as the other POMC-related peptides (first alpha-MSH system). In the rat dorsolateral hypothalamus, we could demonstrate that most neuronal cell bodies stained for MCH also contained immunoreactive alpha-MSH. In the human hypothalamus, neuronal cell bodies stained for MCH were observed only in the periventricular area whereas cell bodies containing alpha-MSH were exclusively located in the infundibular (arcuate) nucleus. In the rat, immunoelectron microscopy showed labelling for MCH in the dense core vesicles of positive neurons and double-staining techniques clearly demonstrated that both immunoreactive MCH and alpha-MSH could be consistently detected in the same dense core vesicles. These ultrastructural studies then suggest that these two peptides should be released simultaneously from neurons located in the rat dorsolateral hypothalamus.     

Effect of dexamethasone implanted in different brain areas on the morphine-induced PRL, GH and ACTH/corticosterone secretion

We studied the effect of dexamethasone (DEX) implantation in male Wistar rats to elucidate the site of action of morphine-induced prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH) and corticosterone (B) secretion. DEX or cholesterol was implanted in the close vicinity of the paraventricular (PVN), or the arcuate nuclei (ARN) of the hypothalamus or into the hippocampus. Five days after implantation blood samples were taken 30 min after i.p. morphine by decapitation or through an indwelling cannula 15, 30, 60 min after i.v. injection. DEX implanted near the PVN resulted in a blockade of morphine-induced ACTH and B secretion. In contrast, GH response to morphine was enhanced, while that of PRL was unchanged. DEX implanted near the ARN significantly inhibited the PRL-releasing effect of morphine, but was without any influence on the PRL secretion induced by haloperidol. There was a partial reduction in the B response to morphine, and GH secretion was unchanged. Dorsal hippocampal implants were without any effect on the morphine-induced GH, PRL or B secretion. We suggest that the site of glucocorticoid inhibitory action in the hypothalamus is the PVN for the opiate-induced ACTH/B secretion, and the ARN for the morphine-induced PRL release. The enhanced GH response to morphine observed in DEX-PVN implanted rats might be due to a decreased somatostatin tone.