摘要:

Thyrotropin-releasing hormone (TRH) has been previously demonstrated to both stimulate growth hormone (GH) secretion and induce refractoriness to subsequent TRH provocation in vivo in chickens. Challenges with TRH at intervals of 1 h evoked different patterns of GH release in anesthetized adult chickens dependent upon TRH dosage. Initially, the administration of TRH at 10 µg/kg increased the plasma concentration of GH. However, the second and subsequent, through to the sixth challenges with TRH did not affect GH release. Plasma concentrations of GH were elevated by repeated injections of TRH (1.0 µg/kg). The magnitude of the response was reduced for the second and third challenges with full recovery of the GH response to the fifth challenge and an enhanced response to the sixth challenge. Similar GH secretory responses to TRH (at 0.1 µg/kg) were observed with the first through fourth challenge but the magnitude of response was again increased for the fifth and sixth challenge. At a lower dose (0.01 µg/kg), TRH did not initially affect plasma concentrations of GH. However, GH release was increased by the third challenge, and subsequent TRH administration evoked progressively larger increases in plasma concentration of GH. It would appear that only high doses of TRH induce refractoriness to subsequent challenge, while lower doses presensitize the pituitary to TRH. If TRH challenges at a dose which provokes the complete refractoriness (10 µg/kg) are administered at intervals of 2, 3 or 4 h, the GH secretory response is consistent for each challenge. The refractoriness to TRH is thus overcome within a period of

ISSN:0028-3835    

DOI:10.1159/000124940

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The ontogeny in the rat hypothalamus of arginine vasopressin (AVP) and corticotropin-releasing factor (CRF) was studied to determine whether these two peptides develop in parallel, given the synergistic effect of AVP with CRF on adrenocorticotropic hormone (ACTH) release. Hypothalami and extrahypothalamic cerebrum of 15-day fetal -40-day postpartum rats were extracted in acetic acid for radioimmunoassay. Both AVP- and CRF-like immunoreactivity was detected in whole brain extracts of 15-day fetuses. Hypothalamic CRF levels were low during fetal life, fluctuated around the time of birth, and then progressively rose to 63% of adult levels by day 21 postpartum. Extrahypothalamic levels of brain CRF paralleled hypothalamic levels. Hypothalamic AVP levels began to rise at fetal day 19 in a stepwise manner, with the greatest rise in levels occurring after day 14 postpartum. At day 21 postpartum hypothalamic levels were only 17% of adult. Extrahypothalamic AVP levels initially paralleled those in the hypothalamus but reached a plateau after day 4 post-partum, and did not rise again until after day 21. Hypothalamic CRF and AVP thus do not develop strictly in parallel; the adult ratios of these peptides (∼1:40) were never seen during development, perhaps of significance in the observed blunting of the hypothalamic-pituitary-adrenal response to stress in infant rat

ISSN:0028-3835    

DOI:10.1159/000124941

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Thymosin fraction 5 (TF-5), a partially purified thymic preparation, has been previously shown to have luteinizing-hormone-releasing-hormone-releasing activity in perfused rat hypothalamus as well as an in vivo stimulatory effect on the pituitary-adrenal axis in prepubertal monkeys. We report here the effect of TF-5 on the plasma levels of several hormones in female rats of different ages. Conscious free-moving Sprague-Dawley rats carrying an indwelling atrial cannula received a single dose of 5 mg/kg body weight of either bovine serum albumin (BSA) or TF-5 via cannula. In young (3–4) months and old (25 months) rats, thymosin induced a marked reduction of plasma thyrotropin (TSH) which was significantly greater than the normal circadian decline observed in the BSA-treated controls. Senescent females (34 months) displayed high basal levels of TSH which showed little circadian rhythmicity and did not respond to TF-5. Thyroxine (T4), triiodothyronine (T3), corticosterone, and prolactin levels were not affected by TF-5 at the dose levels tested. An age-dependent decrease in basal plasma levels of T4 but not T3 was observed in both BSA- and TF-5-treated rats. Young females given up to 10 mg BSA/kg body weight (i.v.) and noninjected controls had similar levels of the above hormones up to 3.5 h after BSA injection. These results suggest that the thymus has an inhibitory action on TSH in the rat, which is not mediated by the thyroid gland. Our results also suggest an age-related desensitization of the TSH system to thymic influence in this specie

ISSN:0028-3835    

DOI:10.1159/000124942

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

To identify the specific thyrotropin-releasing hormone(TRH)-containing neurons projecting to the median eminence (ME), a retrograde tracing method with horseradish peroxidase (HRP) was combined with immunocytochemical staining for TRH. Three days after HRP injection restricted to the ME, several TRH-positive neuronal perikarya were found to contain HRP. Such double-stained cells were exclusively distributed in the anterior parts of the periventricular nucleus and the most medial parts of the paraventricular nucleus. Few double-stained cells were observed in other parts of the brain examined. The present observations appear to demonstrate that the specific TRH neurons projecting to the ME are located along the border of the third ventricle, anterior to the ME.

ISSN:0028-3835    

DOI:10.1159/000124943

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The serotonin (5-hydroxytryptamine, 5-HT) precursor 5-hydroxy-L-tryptophan (5-HTP) and 5-HT antagonists, respectively, are able to stimulate and block pituitary adrenocorticotropin (ACTH) release. However, our previous data do not support a role of central serotoninergic systems in the neural control of ACTH release. We thus examined the hypothesis that 5-HTP given either alone or with uptake-blocking drugs such as fluoxetine caused stimulation of ACTH through activation of central noradrenergic neuronal activity (NNA). The hypothesis was tested in normal adult male rats by correlating medial basal hypothalamic NNA and serotoninergic neuronal activity (SNA) with serum ACTH following administration of 5-HTP (20 and 100 mg/kg, i.p.) in the presence or absence of fluoxetine (10 mg/kg, i.p.) or cyproheptadine (10 mg/kg, i.p.). The α2-adrenergic agonist clonidine (150 µg/kg, i.p.) was used to inhibit central NNA and to examine the role of α2-adrenoceptors in the actions of serotoninergic drugs. Computerized mass spectrometry was employed to specifically and precisely assay hypothalamic norepinephrine (NE), 3,4-dihydroxyphenylethyleneglycol (DHPG), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) to obtain indices of hypothalamic NNA (DHPG/NE) and SNA (5-HIAA/5-HT). The administration of fluoxetine/5-HTP stimulated (p < 0.01) both hypothalamic NNA and ACTH release. Serum ACTH levels significantly correlated with hypothalamic NNA (p < 0.0001) and SNA (p < 0.005), however, multiple linear regression analysis revealed that central NNA (p 0.4) was a significant determinant of ACTH release. Further, clonidine, the inhibitor of NNA, completely blocked (p < 0.01) the ACTH response to fluoxetine/5-HTP. The administration of high-dose 5-HTP resulted in significant stimulation of both hypothalamic NNA and serum ACTH but, in this case, clonidine failed to block 5-HTP-induced ACTH release, despite the inhibition of hypothalamic NNA, and there was no strong relationship between serum ACTH and NNA. However, when cyproheptadine was administered together with 5-HTP there was a small, but significant, suppression of the ACTH response and the strong relationship between serum ACTH and hypothalamic NNA was restored. In the presence of cyproheptadine, clonidine treatment resulted in complete inhibition of the ACTH response to high-dose 5-HTP. Thus, exogenous 5-HTP may stimulate ACTH release via two different mechanisms. The predominant one is mediated centrally via activation of NNA and can be blocked by clonidine but not 5-HT antagonists. The other is due to a direct 5-HT (or 5-HTP) action, apparently not involving hypothalamic monoamine neuronal pathways, and cannot be blocked by clonidi

ISSN:0028-3835    

DOI:10.1159/000124944

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In vivo and in vitro autoradiography with radiolabeled corticosteroid analogs as well as immunocytochemistry with monoclonal antibodies raised against the rat liver glucocorticoid receptor were used to determine the presence and the topography of two corticosteroid receptor systems (type I and type II) in hamster and rat brains. In the rat, the in vivo autoradiograms clearly revealed the retention by the type I receptor of tracer amount of [3H]corticosterone, primarily in the CA1 and CA2 cell field, dentate gyrus and lateral septum. In the hamster, tracer doses of [3H]cortisol were retained not only in the CA1, CA2, dentate gyrus and lateral septum, but also at high level in the CA3 and CA4 areas. In both species, immunocytochemistry showed the widespread distribution of the type II receptor sites in areas such as the hippocampus, lateral septum, hypothalamus (particularly in the paraventricular nucleus), thalamus and cortex (these results were also reflected in the in vitro autoradiography). Strong cell nuclear glucocorticoid immunoreactivity (type II-IR) was observed in the CA1 and CA2 (as well as CA3 and CA4 in the hamster) pyramidal neurons. In the hippocampus of intact animals, type II-IR was seen in the neuronal cell nuclei. Adrenalectomy caused a depletion of the type II-IR signal from the cell nucleus, which returned 1 h following subcutaneous administration of RU 28362 to adrenalectomized animals. The present study thus shows a similar but not identical distribution of the type I and type II receptor systems for corticosteroids in the hamster and rat brains. In contrast to the rat, the CA3 and CA4 cell fields in the hamster hippocampus contain higher numbers of these receptors.

ISSN:0028-3835    

DOI:10.1159/000124954

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The morphological substrate for the central mechanisms that control growth hormone (GH) release in the rat hypothalamus was investigated immunohistochemically by light and electron microscopy. In electron-microscopic studies, a dual immunolabeling technique was employed to demonstrate pairs of peptides, i.e. rat hypothalamic growth hormone-releasing factor (rhGRF) and somatostatin (SRIH), rhGRF and substance P (SP), and rhGRF and methionine-enkephalin-Arg6-Gly7-Leu8 (Enk-8), in different neuronal structures. Immunoreactivity of rhGRF was detected as silver-gold particles and those of the other substances as diaminobenzidine products by preembedding immunostaining procedures. In the external layer of the median eminence, axonal terminals immunolabeled for rhGRF and for SRIH showed the same pattern of distribution and close proximity. The neuronal inputs to GRF cell bodies in the arcuate nucleus were examined, and SRIH, SP and Enk-8 fibers with varicosities were found to form dense networks around the perikarya of GRF neurons, suggesting the presence of synaptic associations. Axonal terminals immunolabeled for SRIH, SP or Enk-8, and unlabeled terminals appeared to form coincidental synaptic junctions on GRF perikarya. These findings suggest that the central regulation of GH release occurs at the levels of the median eminence and the cell bodies.

ISSN:0028-3835    

DOI:10.1159/000124955

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Complete or retrochiasmatic deafferentations of the mediobasal hypothalamus were made in female rats 7 days prior to experimentation in order to determine the role played by putative afferent neuronal connections (1) in maintaining the basal neuronal activity of tuberoinfundibular dopaminergic (TIDA) neurons, and (2) in the stimulatory actions of prolactin on these neurons. The neuronal activity of TIDA neurons was estimated by measuring the rates of synthesis, turnover or metabolism of dopamine (DA) in the terminals of these neurons in the median eminence. Complete deafferentation of the mediobasal hypothalamus reduced the basal rate of DA synthesis, and retrochiasmatic deafferentation decreased the rates of synthesis, turnover and metabolism of DA in the median eminence. A knife cut 1 mm rostral to the retrochiasmatic cut failed to alter basal TIDA neuronal activity. These results suggest that afferent neuronal inputs originating in or coursing through the caudal portion of the anterior hypothalamus mediate a tonic stimulatory influence on TIDA neurons in the female rat. Intracerebroventricular administration of rat prolactin or systemic administration of haloperidol (which increases circulating levels of prolactin) increased DA synthesis in the median eminence of both sham-operated rats and retrochiasmatic-deafferentated rats. Thus, the stimulatory action of prolactin was not blocked by retrochiasmatic deafferentation. In addition, elimination of the basal stimulatory action of endogenous prolactin by pretreating animals with bromocriptine reduced the rate of DA synthesis in the median eminence of both sham- and retrochiasmatic-deafferentated rats. This bromocriptine-induced decrease in DA synthesis was reversed by intracerebroventricular administration of prolactin in both groups. These results suggest that the retrochiasmatic-deafferentation-induced decrease in TIDA neuronal activity is a consequence of removing stimulatory afferent input to these neurons which is mediated by something other than prolactin.

ISSN:0028-3835    

DOI:10.1159/000124956

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Hypothyroidism was induced in rats by treatment with propylthiouracil through the mother’s milk throughout the suckling period followed by surgical thyroidectomy without use of radioiodine. The growth of these animals was considerably retarded and their light-dark discriminative operant learning ability was also significantly decreased. Replacement therapy with thyroxine to maintain its normal serum concentration was effective for continuing normal growth and development of learning ability. Therefore, these hypothyroid rats are a useful model of congenital hypothyroidism. Biochemical studies showed that the inhibition of cerebral NaK-ATPase and succinic dehydrogenase activities detected in early postnatal life in these hypothyroid rats was transient and that normal activities of these enzymes were later regained in adult rats. However, the activity of 2’,3’-cyclic nucleotide 3’-phosphohydrolase and the brain myelin remained low throughout life unless thyroxine was administered. Though a critical correlation between biochemical parameters and learning ability is still uncertain, these results suggest that the formation of myelin in the neonatal period is at least dependent on thyroid hormone and would play an important role in mental deve

ISSN:0028-3835    

DOI:10.1159/000124945

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

To study the role of the hypothalamus in the regulation of growth hormone (GH) synthesis, the rate of amino acid incorporation into GH in vitro was examined in rats with anterolateral deafferentation of the medial basal hypothalamus. Amino acid incorporation into GH (GH synthesis) decreased significantly 7 days after the deafferentation, although prolactin synthesis did not show any significant fluctuations. The serum GH was increased, while the pituitary GH content was decreased. Somatostatin in the stalk median eminence of such deafferentated animals decreased markedly, while GH-releasing hormone was decreased slightly but not significantly. Immunohistochemical examinations revealed that the number of somatostatin nerve terminals in the median eminence decreased markedly, while GH-releasing hormone nerve terminals in the same area remained intact. These findings suggest that neural factor(s) outside the medial basal hypothalamus plays an important role in the regulation of GH synthesis.

ISSN:0028-3835    

DOI:10.1159/000124946

出版商:S. Karger AG    

年代:1988

数据来源: Karger