摘要:

Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y(NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.

ISSN:0028-3835    

DOI:10.1159/000126435

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The relative importance of the paraventricular (PVN) and the supraoptic nuclei (SON) for the secretion of oxytocin was evaluated by comparison of stress-induced oxytocin release under normal conditions, in the absence of vasopressin and/or corticoliberin (CRF). We introduced an incomplete anterolateral cut (iALC) around the mediobasal hypothalamus designed to leave intact the SON-neurohypophysial connections but to inflict damage to the nerve fibers from the PVN. The studies were performed in conscious cannulated rats using immobilization as the stress stimulus. Stress-induced oxytocin release was found in heterozygous Brattleboro rats as well as in homozygous animals lacking vasopressin, yet in the latter it was less pronounced and in both cases it was prevented by iALC. In Wistar rats, stress-induced oxytocin release was markedly reduced after iALC and absent after PVN lesion. Both hypothalamic interventions failed to influence basal oxytocin levels and resulted in a similar reduction of ACTH release. It is concluded that a functional diversity exists between the hypothalamic magnocellular nuclei. At least in relation to immobilization stress, the PVN is essential for stress-induced oxytocin release and it is evident that the SON without the PVN cannot preserve oxytocin secretion during stress.

ISSN:0028-3835    

DOI:10.1159/000126436

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The aims of the present study were to investigate the sexual dimorphism and the role of sex steroids in GH secretion at the pituitary level, and to evaluate the ontogenesis of these effects. Towards these aims we used an in vitro perifusion system of hemipituitaries under a simulated milieu of hypothalamic factors: two 3-min pulses of GHRH at 3-hour intervals were separated by continuous flow of somatostatin. Rat GH was measured in 2.4-min fractions and analyzed by the pulse analysis program PULSAR. Pulses were similar in pre-pubertal male and female rats, but sexual dimorphism was evident in adults. In adult males, who had undergone neonatal gonadectomy, GH pulse amplitude and area under the curve (AUC) were lower compared to control. When gonadectomy had been performed at a prepubertal age, the pulse amplitude was still lower, but the AUC was not different from control. The gap between orchiectomy at neonatal and prepubertal age indicates the perinatal imprint, which induces an increase in AUC. Neonatal testosterone treatment of intact female rats had no effect on GH secretion by adult pituitaries. In neonatally gonadectomized female rats, under neonatal testosterone treatment, the pulse amplitude increased. A similar increase was observed after neonatal gonadectomy without testosterone treatment. We conclude that the sexual dimorphism of GH secretion is partially induced at the pituitary level and its response to the hypothalamic hormones. We assume that a neonatal imprint effect of testosterone in the male induces primarily an increase in AUC in response to GHRH. The imprint in females influences the GH pulse amplitude and AUC.

ISSN:0028-3835    

DOI:10.1159/000126437

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Guinea pig magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) were studied using the in vitro slice preparation. Intracellular recordings were made with biocytin-fïlled electrodes, permitting immunocytochemical identification of the recorded cells as arginine vasopressin- (AVP) versus oxytocin- (OT) containing. Only AVP cells displaying a depolarizing potential (DP) fired phasically. The DP was associated with a transient inward current measured in voltage clamp, which exhibited a number of properties of the T-type calcium current: activation threshold of –64 mV, time course of up to 250 ms, blockade by nickel and augmentation by barium chloride. This current has not been reported previously in SON neurons. The T-type current (It) was always associated with a damped oscillation of the membrane following the offset from hyperpolarizing steps. In all cells tested, an apamin-sensi-tive afterhyperpolarization (AHP) was observed, similar to the calcium-dependent potassium current (Iĸ, ca) described in rat SON and other CNS regions. Therefore, as with other CNS regions displaying damped oscillations, guinea pig SON cells possess both an IT and an IK, ca. We have previously described an Ih activating at hyperpolarized potentials in these cells, which depolarizes the membrane to a range in which the It and IK, ca can interactively support oscillations. In summary, the It and associated depolarizing potential appears to be a requisite feature for phasic firing in AVP cells of guinea pig

ISSN:0028-3835    

DOI:10.1159/000126438

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Our recent studies indicate that lipocortin 1 (LC1), a putative second messenger protein for the anti-inflammatory steroids in peripheral tissues, may also contribute to the regulatory actions of the glucocorticoids on the hypothalamo-pituitary-adrenal axis. In the present study we have used in vitro and in vivo models to compare the effects of adrenalectomy, LC1 and dexamethasone on the cytokine-induced secretion of the 41-amino acid corticotrophin releasing factor (CRF-41) and arginine vasopressin (AVP) by the rat hypothalamus. In addition, western blot analysis was used to examine the influence of dexamethasone on the expression of LC1 in the hypothalamus. In vitro, interleukins- (IL-) 1α (100 and 200 pg/ml), 1β (0.5 and 1.0 ng/ml) and 8 (0.25-1.0 ng/ml) readily initiated the release of CRF-41 and AVP from hypothalami removed from intact rats. IL-6 (10 and 20 ng/ml) was also an effective CRF-41 secretagogue but, unlike the other interleukins tested, it was ineffective with regard to AVP. Adrenalectomy 7-14 days prior to autopsy increased significantly (p < 0.01) the magnitude of the CRF-41 responses to IL-1α, IL-1β and IL-6 but not to IL-8. In contrast however, while hypothalamic tissue from adrenalectomized rats, unlike that from intact animals, responded to IL-6 (5-20 ng/ml) with a pronounced hypersecre-tion of AVP, the AVP responses to IL-1α and IL-1β were largely unaffected by adrenalectomy as too were those to IL-8. The marked increases in CRF-41 and AVP release from hypothalami from adrenalectomized rats initiated in vitro by IL1α, IL-1β, IL-6 and IL-8 were readily overcome by preincubation of the tissue with dexamethasone (10-7M). In addition, the steroid caused ‘externalization’ of two species of immunoreactive (ir-) LC1 (37 and 58 kDa) by the hypothalamic cells but failed to influence the total LC1 content of the tissue. The inhibitory effects of dexamethasone on the cytokine-induced release of CRF-41 in vitro were mimicked by LC 1(10 ng/ml) which alone had no effect on the basal release of the peptide. However, unlike dexamethasone, LC1 failed to influence the concomitant release of AVP from the hypothalamic tissue elicited by IL1α, IL-1β or IL-8 and potentiated that evoked by IL-6. In vivo central administration of IL-1β (5-10 ng in 3 µl) or IL-6 (7.5-30 ng) in 3 µl) via an indwelling intracerebroventricular (i.c.v.) cannula initiated significant (p < 0.01) dose-dependent increases in the serum corticosterone concentration; these responses were inhibited by prior injection into the third ventricle of LC1 (0.3-1.2 µg/3 µl, i.c.v.) which alone, in the highest dose tested, precipitated a small increase in corticosterone release. The results support the concept that cytokines play a key role in initiating the release of CRF-41 from the hypothalamus and provide novel evidence to suggest that the acute inhibitory effects of the corticosteroids on these responses may be mediated in part by LC1. In addition they demonstrate the ability of certain cytokines to stimulate the release of AVP from isolated hypothalamic tissue and indicate that, although these effects are dexamethasone sensitive, they are

ISSN:0028-3835    

DOI:10.1159/000126439

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Courtship clasping of females by male roughskin newts (Taricha granulosa) is rapidly blocked by exposure to corticosterone (CORT). This behavioral effect appears to result from CORT binding to a receptor in neuronal membranes. The present study investigated effects of intraperitoneal CORT administration on neurophysiological properties of extracellularly recorded single medullary neurons in acutely prepared newts. CORT produced multiple neurophysiological effects that emerged within 3 min of injection and increased in magnitude during the next 20-30 min. Spontaneously active and sensory-responsive neurons showed a decline or cessation of firing concomitant with a loss of sensory responsiveness, especially to cloacal pressure, a clasp-facilitating stimulus in behaving newts. After CORT administration, reticulospinal neurons that were backfired (antidromically activated) by spinal cord stimulation, exhibited reduced antidromic action potential amplitude, slowed rates of spike generation and other indications of reduced excitability. Comparable effects of CORT were also evident in newts with a premedullary brainstem transection, indicating a direct hormone action on the caudal neuraxis. Dexamethasone (DEX), a glucocorticoid that binds poorly to the CORT membrane receptor and has little effect on clasping, had little or no direct neurophysiological effect, but DEX injection 30 min before CORT interfered with the neurophysiological action of CORT. The rapidity, time course and specificity to CORT of these neurophysiological effects are consistent with mediation through the CORT membrane receptor. In addition, the pattern and dose sensitivity of these neurophysiological actions plus their occurrence in the medulla, suggest that they could underlie the CORT effect on courtship clasping.

ISSN:0028-3835    

DOI:10.1159/000126440

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The growth-promoting activities of tumor-conditioned media (TU-CM) obtained from 23 cultured human nonfunctioning pituitary adenomas were studied in vitro. TU-CM obtained from adenoma cell cultures increased both cell counts (range: 108-179%; control = growth in serum-free medium = 100%) and 3H-thymidine incorporation (112-139%) of rat pituitary cell cultures, indicating that TU-CM contains growth-stimulating substances. TU-CM was also able to stimulate the growth of normal fibroblasts (3H-thymidine incorporation: 164-178%; cell counts: 145–157%) and endothelial cells (3H-thymidine incorporation: 131–149%; cell counts: 181-217%), suggesting the presence of – possibly angiogenic – growth factors that act on these cell types. However, the growth of hormone-producing cells was also stimulated, since TU-CM increased 3H-thymidine incorporation into rat pituitary cells in the presence of D-Val-MEM, a medium specifically inhibiting growth of fibroblasts. Addition of neutralizing antibodies against transforming growth factor alpha (TGF-α), epidermal growth factor (EGF), insulin-like growth factor I (IGF-1) and basic fibroblast growt factor (bFGF), either alone or in different combinations, reduced the growth-promoting activity of TU-CM on rat pituitary cells (range: 96–71%; control = growth effect of TU-CM without antibodies = 100%), strongly indicating the presence of these growth factors in TU-CM. All 4 antibodies together completely inhibited the growth-stimulatory activity of TU-CM, strongly suggesting that these growth factors play the major role among growth-stimulating substances in TU-CM. This is the first study giving evidence that TGF-α, EGF, IGF-I and bFGF are secreted by nonfunctioning adenoma cells indicating that the growth factors could be involved in growth regulation of pituitary adenomas by paracrine or autocrine

ISSN:0028-3835    

DOI:10.1159/000126441

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The release of endogenous noradrenaline in the anterior hypothalamus was studied with microdialysis perfusion in freely moving rats that were subjected to immobilization stress. Experiments were carried out in sham-adrenalecto-mized and adrenalectomized rats that were first given drinking water containing corticosterone for 5 days following surgery and then switched to a corticosterone-free diet the day before stress application. One group of these adrenalectomized animals was injected with dexamethasone. Basal release of noradrenaline collected in 20-min fractions was similar in the three groups of animals and averaged 24 fmol. The recovery of the probe was about 10%. In sham-adrenalectomized rats application of 20-min immobilization stress increased noradrenaline release to 310% of baseline in the sample collected during stress application. A significant increase (+175% of baseline) was still observed in the next 20-min sample. Subsequent values were all identical to baseline. In adrenalectomized rats lacking exogenous corticosterone the stress-induced release of noradrenaline was prolonged with noradrenaline levels remaining elevated for 2 h after the onset of stress. The total noradrenaline release during this entire period was about 2.5 times higher in adrenalectomized than in sham-operated rats. However, the maximal increase during the period of immobilization was not significantly affected. Treatment with dexamethasone prevented the prolonged increase in noradrenaline release but did not affect the increase during the period of stress. While glucocorticoids do not appear to affect the increased release of NA in the anterior hypothalamus during the period of stress, they act to limit the duration of this activation after the application of stress. Our results show that glucocorticoids affect the stress-induced activation of the catecholaminergic systems innervating the anterior hypothalamus, i.e. the region of the paraventricular nucleus, and suggest that glucocorticoids exert on these systems a homeostatic, rather than a negative feedback, regulation during their stress-induced activation.

ISSN:0028-3835    

DOI:10.1159/000126442

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Glucocorticoids are known to decrease growth hormone (GH) secretion in man. Galanin, a 29-amino acid peptide, and arginine stimulate GH secretion through different hypothalamic mechanisms. The aim of our study was to investigate the effect of arginine and galanin (alone or in combination) on GH secretion in 7 adult patients with nonendocrine diseases receiving chronic daily immunosuppressive glucocorticoid treatment (5 F, 2 M; mean age 48.4 ± (SEM) 3.7 years). Five normal adults (3 F, 2 M; mean age 34.6 ± 2.2 years) served as controls. All subjects underwent in random order: (1) infusion of arginine hydrochloride (30 g i.v. in 100 ml saline) from -30 to 0 min; (2) infusion of synthetic porcine galanin (500 µg i.v. in 100 ml saline) from -15 to 30 min; (3) intravenous infusion of arginine hydrochloride from -30 to 0 min combined with synthetic porcine galanin from -15 to 30 min. In normal subjects GH peak after arginine (8.6 ± 3.3 µg/1) and galanin (6.6 ± 3.2 µg/1) did not show significant differences; the GH peak after arginine + galanin (21.4 ± 6.1 µg/1) was significantly higher with respect to galanin or arginine alone. In glucocorticoid-treated patients the GH peak after arginine (4.6 ± 1.5 µg/1) was significantly (p < 0.05) higher with respect to galanin (1.8 ± 1.0 µg/1); after arginine + galanin the GH peak (8.2 ± 2.3 µg/1) was significantly (p < 0.05) enhanced with respect to either galanin or arginine alone. The GH response to arginine was not significantly different in normal and glucocorticoid-treated patients. Normal subjects showed higher GH peaks after galanin alone and arginine + galanin with respect to the steroid-treated group. Moreover, we hypothesize that the inhibitory action of glucocorticoids on GH secretion in man is mediated not only by an increase in somatostatin tone but also by a decrease in endogenous hypothalami

ISSN:0028-3835    

DOI:10.1159/000126443

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Neuronal histamine (HA) in the central nervous system (CNS) has been implicated in control of peripheral cardiovascular and neuroendocrine responses. The tuberomammillary nucleus (TMN) of the posterior hypothalamus contains all CNS HA cell bodies. In these experiments, the TMN was electrically stimulated in conscious rats and HA release in the region of the supraoptic nucleus (SON) was estimated using in vivo microdialysis. In addition, mean arterial blood pressure (MAP), heart rate (HR), and plasma concentrations of norepinephrine (NE) and vasopressin (VP) were measured before, during and following TMN stimulation. Stimulation of the TMN resulted in a significant increase in extracellular HA (110 ± 29% control) in the region of the SON. MAP, HR and plasma NE concentration were also significantly elevated during TMN stimulation. However, plasma VP concentrations were unchanged. These results show that TMN stimulation in conscious animals releases HA in the region of the SON and is associated with a pressor response, tachycardia, and increased plasma concentration of NE, but not release of VP

ISSN:0028-3835    

DOI:10.1159/000126444

出版商:S. Karger AG    

年代:1993

数据来源: Karger