摘要:

In vitro quantitative autoradiography and the microdissection technique of Palkovitz were used to examine the effects of estradiol-17β on GABAAreceptors and on glutamic acid decarboxylase in discrete areas of rat brain. Under the conditions examined, estradiol did not affect glutamic acid decarboxylase activity. However, treatment with estradiol decreased Gabaa receptor binding in a majority of areas that contain high levels of intracellular estradiol receptors and in a number of areas that contain few or no estradiol receptors. Within one brain area, the ventromedial nucleus of the hypothalamus, the estradiol effect was mapped and found to occur within the estradiol-sensitive ventrolateral portion and the surrounding dendritic plexus. Time- and dose-response relationships were region specific suggesting that estradiol might influence GABAA-receptor binding through multiple mechanisms. Estradiol does not appear to interact directly with Gabaa receptors since addition of estradiol to the assay system did not affect binding. Our findings suggest that one way estradiol might affect neuroendocrine and other centrally mediated processes is through effects on GABAA-receptor binding

ISSN:0028-3835    

DOI:10.1159/000124958

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

These studies were designed to assess whether a decline in pituitary response to growth hormone-releasing factor (GRF) contributes to the decline in amplitude of growth hormone (GH) pulses with age. Atrial cannulated young (3–4 months), middle-aged (12–14 months) and old (20–22 months) Fischer 344 male rats were anesthetized with pentobar-bital to suppress pulsatile release of GH. One hour later, animals were injected with hpGRF(l-44) (10 µg/kg) and blood samples were removed at 0, 5, 10, 20, 40 and 80 min. Animals were then passively immunized with somatostatin antiserum and hpGRF(l-44) was reinjected. Samples were removed at the time intervals previously described. In response to 10 µg/kg GRF, plasma GH in young and middle-aged animals increased to 921 ± 105 and 866 ± 126 ng/ml, respectively, at 10 min and declined. In old animals, GH concentrations only increased to 654 + 80 ng/ml (p < 0.05 compared to young rats). This represents a 28% reduction in the peak GH response to GRF. Despite passive immunization with somatostatin anti-serum, the peak GH response to a second injection of GRF was diminished in all age-groups. However, integration of the area under the response curve indicated that GH secretion was similar in young and old animals during the 80-min sampling period after somatostatin antiserum. In another study, diethyldithiocarbamate (DDC; 250 mg/kg, i.v.), a dopamine-β-hydroxylase inhibitor, was used to inhibit pulsatile GH release. One hour later, animals were injected with hpGRF(l-44) (50 µg/kg, i.v.) and blood samples were removed as previously described. At the end of this sampling period, animals were passively immunized with somatostatin antiserum and the GH response to 0.5 and 5 µg/kg GRF was studied. In response to 50 µg/kg GRF, plasma GH increased to approximately 130 ng/ml in all age-groups at 10 min and declined. No age-related differences in the GH response to GRF were observed in the three age-groups. In the presence of somatostatin antiserum, a dose-related increase in plasma GH was found in all age-groups and the rise in GH was greater in old as compared to young rats (p < 0.05 at 10 and 20 min after injection). Studies of the time course and dose-response characteristics of GH release from in vitro pituitary slices of young, middle-aged and old rats were similar in response to 109–107M hpGRF( 1 -44) although basal GH release was reduced by 44–53% in old as compared to young rats (p < 0.05). These results demonstrate that (1) the diminished response of aging rats to GRF in vivo is dependent on the pharmacological treatments used to inhibit pulsatile release of GH, (2) after passive immunization with somatostatin antiserum, pituitary GH response to GRF is equal to or greater in old as compared to young rats and (3) the temporal and dose-response characteristics of freshly prepared pituitary tissue are similar in animals of all age-groups. Our results suggest that diminished GH release with age is not associated with decreased pituitar

ISSN:0028-3835    

DOI:10.1159/000124959

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The present studies were carried out to investigate the mechanisms through which systemic angiotensin II (AII) acts within the central nervous system to influence the release of anterior pituitary hormones in the Sprague-Dawley rat. In particular, these studies have examined the role of the subfornical organ (SFO) as an essential structure mediating these responses. Extracellular single-unit recordings were obtained from 199 paraventricular nucleus (PVN) neurons anti-dromically identified as projecting to the median eminence. Different groups of these neurons were tested for the effects of either electrical stimulation in the SFO (n = 87) or systemic AII administration in intact (n = 49) and SFO-lesioned (n = 25) animals. Of cells tested with SFO stimulation 45% were excited, 16% inhibited, and the remainder unaffected. Neurons which were excited were primarily located just medial to the magnocellular neurons in the region where the majority of corticotropin-releasing hormone immunoreactive cells are found. In contrast, inhibitory responses were observed in cells located in the dorsal medial PVN, a region containing thyrotropin-releasing hormone, somatostatin, and dopamine PVN-median eminence neurons. Following systemic AII 42% of cells tested showed increased activity specific to the effects of this peptide, and 20% showed alterations in activity associated with the cardiovascular changes induced by AII. In contrast, following SFO lesion only 8% of neurons tested showed specific excitatory responses to AII. In order to test the hypothesis that systemic AII may activate this excitatory SFO to PVN pathway, a further group of 35 neurons were tested with both SFO stimulation and AII. Excitatory responses to AII were observed in 13 of these cells, each of which was also excited by SFO stimulation. These studies describe mechanisms through which the central nervous system may sense peripheral concentrations of peptide hormones and modulate the activity of neural pathways which in turn influence the activity of PVN neurons which control the secretion of anterior pituitary hormones.

ISSN:0028-3835    

DOI:10.1159/000124960

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The site of action of delta-9-tetrahydrocannabinol (THC) to inhibit the release of prolactin (PRL) and growth hormone (GH) was examined by in vivo and in vitro experiments. In conscious freely moving animals bearing implanted third ventricular (3 V) and external jugular cannulae, THC or the diluent was microinjected into the 3 V and blood samples were removed to determine the effect on plasma PRL and GH. Both the 0.4- and 4-µg dose injected intraventricularly resulted in a suppression of PRL and GH release as indicated by declines in plasma levels within 40–80 min which were highly significant statistically but not dose-related. The higher dose evoked a pulse of GH and/or PRL in most animals which preceded the lowering of hormonal levels. In the in vitro experiments dipersed anterior pituitary cells were incubated with 5 × 10–8 or 5 × 10–9M THC or the diluent for 5 days. Fresh culture medium was added to the cells after 3 days and the cells cultured for an additional 2 days. After this period, the cells were incubated for an additional 2 h in culture medium with or without THC plus a near maximal dose of thyrotropin-releasing hormone and GH-releasing factor (50 and 10 ng/ml, respectively) or the diluent to evaluate the response of PRL and GH release, respectively. Neither dose of THC altered the release or storage of the two hormones during culture or affected the response to the releasing hormones which is suggestive that there is no direct effect of THC on either GH or PRL release. The results of the combined in vivo and in vitro studies indicate that the action of THC to suppress PRL and GH release is mediated within the CNS probably by suppression of aminergic activity and peptide

ISSN:0028-3835    

DOI:10.1159/000124961

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The effects of an opiate receptor antagonist, naloxone, on the in vivo release of luteinizing hormone releasing hormone (LHRH) in ovariectomized and intact female rats were examined using push-pull perfusion. Hypothalamic LHRH release rates were determined before and after naloxone (2.5 mg/kg s.c.) or saline vehicle injection in rats during metestrus or 4 or 8 days following ovariectomy. Naloxone was found to be equally effective in significantly (p < 0.05) stimulating LHRH release in all three treatment conditions. In animals that were fitted with atrial catheters instead of push-pull cannulae, naloxone administration led to significant increases in peripheral LH levels in metestrous and ovariectomized rats. Peripheral follicle-stimulating hormone levels were unaffected by naloxone. These results suggest that opioid inhibitory tone is not diminished during pituitary escape from ovarian negative feedback in adult female rats. Our findings are not consistent with the hypothesis that ovarian negative feedback regulation of LH secretion is serially mediated by endogenous opioid peptide neurons in these animals. Rather, it is proposed that opioid inhibition of LHRH release and ovarian negative feedback may operate in parallel to control LH secretion in the female rat.

ISSN:0028-3835    

DOI:10.1159/000124962

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Neuropeptide Y (NPY) has recently been localized in the rat hypothalamus. In order to evaluate the putative effects of NPY on pituitary function, its action was examined on anterior pituitary cells in culture. Also, an immunocytochemical method was used with the aim of localizing endogenous NPY-like material at the cellular and subcellular levels of the pituitary gland. In vitro studies using dispersed anterior pituitary cells indicated that NPY (10–6 to 10–9M) increased the secretion of luteinizing hormone, growth hormone and prolactin, whereas β-lipotropin hormone and thyrotropin secretions were not affected. The presence of endogenous NPY was demonstrated in gonadotrophs, somatotrophs, corticotrophs and some lactotrophs, but not in thyrotrophs. In immunoreactive cells, NPY-like material was detected in the cytoplasmic matrix, in the secretory granules and in the nucleus distributed primarily in the euchromatin, in the vicinity of the heterochromatin. NPY-like immunoreactivity was also observed at the plasma membrane but only scarcely. These biochemical and immunocytochemical results indicate that NPY may play a direct regulatory role in adenohypophyseal secre

ISSN:0028-3835    

DOI:10.1159/000124963

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

During an investigation of the role of the mediobasal hypothalamus in the regulation of renin secretion from the kidneys, we found that lesions of the ventromedial nuclei prevented the increase in plasma renin activity produced by p-chloroamphetamine. In the present study, we tested the effects of bilateral electrolytic lesions of the ventromedial nuclei on the increase in plasma renin activity produced in sham-operated rats by immobilization, head-up tilt under inactin anesthesia, and a low-sodium diet. Ventromedial lesions reduced or abolished the plasma renin activity increase to all three stimuli without any change in plasma angiotensinogen. The plasma renin concentration responses to immobilization and a low-sodium diet were also reduced. All these stimuli probably exert their effect by way of the sympathetic nervous system. The data support the hypothesis that the ventromedial nuclei or neural fibers passing through them are important in the renin response to diverse stimuli that act by way of sympathetic discharge.

ISSN:0028-3835    

DOI:10.1159/000124964

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

To investigate catecholamine regulation of adrenocorticotropic hormone (ACTH) and vasopressin (VP) release, the relationship of alpha-adrenergic receptor-binding sites to corticotropin-releasing factor (CRF) and VP-containing cell populations within the paraventricular nucleus (PVN) of the hypothalamus was studied. Immunohistochemistry for CRF and neurophysin-vasopressin (NP-VP) was combined with receptor autoradiography. The adrenergic antagonist [3H]-prazosin was used to visualize alpha-1-binding sites and the agonist [3H]-p-aminoclonidine to visualize alphas-binding sites. To determine if changes in adrenergic binding accompanied experimentally induced increased activity of CRF-and VP-containing neurons, adrenalectomy was used as a stimulus for CRF release and dehydration as a stimulus for VP release. Quantitative assessment of autoradiograms revealed a greater density of alpha-1- and alpha-2-binding sites over the medial, parvocellular, CRF-containing region of PVN as compared to the lateral, magnocellular, NP-VP-containing region of the nucleus in all animal groups. Following 10 days of dehydration, the density of alpha-1 – and alpha-2-binding sites associated with the CRF- and NP-VP-containing regions of PVN decreased. At 14 days postadrenalectomy the density of alpha-2-binding sites associated with CRF- and NP-VP-containing regions of the nucleus decreased, but the density of alpha-1-binding sites was unchanged. Results of this study support the hypothesis that epinephrine and/or norepinephrine regulate the release of ACTH and vasopressin via alpha-1- and alpha-2-adrenergic receptors associated with CRF- and VP-containing somata within the PV

ISSN:0028-3835    

DOI:10.1159/000124965

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The radiolabelled somatostatin analogs [125I-Tyr°, Z)Trp8]S14 and [Leu8, DTrp22, l25I-Tyr25]S28 were used as radioligands to study the distribution of somatostatin receptors in the rat hypothalamus. Previous studies have detected very few somatostatin-binding sites in the hypothalamus using in vitro autoradiography. Since the lack of autoradiographic labelling has been ascribed to the occupancy of the receptors by endogenous ligands, we have developed a method using guanosine triphosphate (GTP) pretreatment to unmask somatostatin receptors. Preincubation of brain slices with 10–6M GTP, by desaturating the occupied receptors, made it possible to reveal the wide distribution of somatostatin-binding sites in the rat hypothalamus. Somatostatin-14 binding site populations were observed in numerous hypothalamic areas including the preoptic area where the receptors likely account for self-inhibition of somatostatin release, the supraoptic nucleus, the bed nucleus of the stria terminalis, the anterior hypothalamic nucleus, the perifornical area, the zona incerta and a mediolateral area located laterally to the ventromedian and dorsomedian nuclei and limited laterally by the mammillo-thalamic tract, the fornix and the optic tract. All structures showing S14-binding sites were labelled by the S28 radioligand. In addition, the paraventricular parvocellular nucleus contained exclusively S28-binding sites, which could be involved in the inhibitory effect of S28 on CRF-mediated endocrine and sympathetic responses. A moderate density of S28-preferring sites was also detected in the periventricular nucleus. In summary, GTP preincubation of brain slices appeared to be a useful technique to reveal multiple somatostatin receptors populations in the brain. The widespread distribution of somatostatin receptors in the hypothalamus is in total agreement with the variety of physiological effects of the somatostatin peptide fami

ISSN:0028-3835    

DOI:10.1159/000124966

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In vitro and in vivo perfusion techniques were used to examine the changes in the release of β-endorphin, methionine-enkephalin (met-enkephalin), dynorphin and luteinizing hormone releasing hormone (LHRH) in response to the corticotropin releasing factor (CRF) receptor antagonist, α-helical CRF9–41. All four peptides were measured in the same sample collected at each time interval by specific radioimmunoassay methods. In vitro release experiments were conducted using slices of hypothalami obtained from male rats whereas the in vivo release of these peptides was assessed in push-pull perfusates of the arcuate-median eminence (ARC-ME) region of the medial basal hypothalamus of chloral hydrate-anaesthetized male rats. Treatment of rat hypothalamic slices in vitro with α-helical CRF9–41 (10–6M) resulted in a significant suppression of the release of β-endorphin and met-enkephalin within 10 min of application of the antagonist and a coincident significant increase in the release of LHRH. The levels of dynorphin were reduced but these changes were not significant. Within 10 min of withdrawal of the receptor antagonist and perfusion with normal (antagonist-free) medium the levels of these peptides returned to pretreatment values, i.e. the levels of β-endorphin, met-enkephalin and dynorphin rose while those of LHRH fell. Comparable results were obtained in vivo during push-pull perfusion of the ARC-ME region with α-helical CRF9–41. These concomitant temporal changes in the release of opioid peptides and LHRH in response to the receptor antagonist of CRF support the view that one of the mechanisms by which CRF inhibits the secretion of LHRH is by its stimulation of the release of opioid peptides within the brain. The data further suggest that the activity of opioidergic and LHRH neurons may be continuously under the influence of e

ISSN:0028-3835    

DOI:10.1159/000124967

出版商:S. Karger AG    

年代:1988

数据来源: Karger