摘要:

Mice homozygous for the recessive ‘Ames’ dwarf mutation have undetectable serum or pituitary prolactin (PRL). Accompanying this pituitary deficiency is a marked reduction of dopamine (DA) and its rate-limiting synthetic enzyme tyrosine hydroxylase (TH) in PRL-regulating tuberoinfundibular hypothalamic neurons. In order to determine whether this deficit in adult Ames dwarf mice is congenital or arises postnatally, brains of dwarf (df/df) and normal (DF/?) littermate mice were assessed for TH immunoreactivity from 7 days through 2 months of age. Numbers of TH-positive neurons were counted in three hypothalamic DA areas: tuberoinfundibular A12, medial zona incerta A13, and anterior periventricular A14. There was an increase in the number of TH-positive neurons between 7 and 21 days of age in A12 and A14, but not in A13, for both DF/? and df/df mice. Between 21 days and 2 months of age, cell numbers were the same in all three areas in DF/? mice and in Al 3 and A14 in df/df mice. However, A12 TH-positive cell number in dwarfs decreased significantly (p < 0.01) between 21 days and 2 months, and was markedly lower (p < 0.001) in df/df than in DF/? mice at 2 months of age. The results emphasize the specificity of the dopaminergic neuron reduction in the Ames dwarf, which is restricted to the PRL-regulating tuberoinfundibular region. The data also indicate that the dwarf DA/TH deficit has an onset in late postnatal development, suggesting a response to absence of target PRL, rather than a primary hypothalamic effect of the dwarf mutat

ISSN:0028-3835    

DOI:10.1159/000126658

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The purpose of the present study was to examine the role of estrogen and prolactin in determining the responsiveness of tuberoinfundibular dopaminergic (TIDA) neurons to ĸ-opioid receptor blockade in female rats. TIDA neuronal activity was estimated by measuring either dopamine synthesis [accumulation of 3, 4-dihydroxyphenylalanine (DOPA) 30 min after the administration of the decarboxylase inhibitor NSD-1015] or metabolism [concentrations of 3, 4-dihydroxyphenylacetic acid (DOPAC)] in terminals of these neurons in the median eminence. Blockade of ĸ-opioid receptors with the selective ĸ-antagonist norbinaltorphimine (NOR-BNI) increased the concentrations of DOPAC in the median eminence of ovariectomized rats but had no effect in gonadally intact rats, suggesting that loss of endogenous ovarian hormones following ovariectomy results in an increase in K-opioid-receptor-mediated inhibition of TIDA neurons. Estrogen administration to ovariectomized rats blocked NOR-BNI-induced increases in median eminence DOPAC concentrations, whereas treatment of gonadally intact or ovariectomized, estrogen-treated rats with prolactin antiserum had no effect on the insensitivity of these neurons to NOR-BNI. Administration of antiserum to dynorphin A1–8 increased DOPA accumulation in the median eminence of ovariectomized but not estrogen-treated ovariectomized rats. Taken together, these results reveal that estrogen, acting via a prolactin-independent mechanism, suppresses ĸ-opioid-receptor-mediated inhibition of the activity of TIDA neurons, possibly by decreasing the release of endogenous dyno

ISSN:0028-3835    

DOI:10.1159/000126659

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Effects of thyroxine (T4) on the secretion of thyrotropin-releasing hormone (TRH) and catecholamines into hypophysial portal blood and on the concentrations of arterial plasma thyroid-stimulating hormone (TSH) and prolactin (PRL) in ovariectomized and thyroidectomized (Ovx-Tx) rats were studied. Immediately after ovariectomy, rats were Tx or sham Tx. The Ovx-Tx rats were injected subcutaneously with estradiol benzoate (EB, 0.5 µg/kg b.w.) or sesame oil, and T4 (20 µg/kg b.w.) or saline once daily for 2 weeks. The Ovx rats with intact thyroid gland were injected with saline and oil only. The hypophysial portal blood samples were collected and mixed with or without 2, 3-dimercaptopropanol before extraction by methanol or perchloric acid, respectively. The femoral arterial blood was also collected. The concentrations of TRH in methanol-extracted portal plasma and that of TSH and PRL in arterial plasma were measured by radioimmunoassay. The concentrations of catecholamines in perchloric acid-extracted portal plasma samples were measured by radioenzymatic assay. Thyroidectomy in Ovx rats resulted in an increase in portal plasma TRH and arterial plasma TSH. Despite the presence or absence of estradiol, T4 replacement in Ovx-Tx rats decreased portal plasma TRH and arterial plasma TSH to euthyroid levels. Combination of the injection of T4 and EB in vivo caused significantly decreased levels of portal plasma dopamine and increased arterial plasma PRL compared with those in vehicle-injected Ovx-Tx animals. Concentrations of neither norepinephrine nor epinephrine in hypophysial portal plasma paralleled the altered concentrations of PRL or TSH in arterial plasma. These findings indicate that the negative feedback control of thyroid hormones on the secretion of pituitary TSH is due, at least in part, to inhibition of secretion of TRH into hypophysial portal blood, and that thyroxine potentiates the stimulatory effect of estradiol on the secretion of pituitary PRL by inhibition of secretion of dopamine into hypophysial portal bloo

ISSN:0028-3835    

DOI:10.1159/000126660

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In addition to the magnocellular hypothalamic nuclei, arginine vasopressin (AVP)-containing neurons have also been identified in limbic structures, including the hippocampus and amygdala. In the present study, we compared the qualitative properties of the in vitro release of AVP from the dissected hypothalamus with the in vitro release from the dissected amygdala and used these release systems to evaluate the interactions with neurotransmitters and cytokines. The areas of the paraventricular nucleus and supraoptic nucleus that contain the AVP neurons and that receive cholinergic innervation are also interleukin (IL)-1β immunoreactive. Acetylcholine or high KC1 (60 mM) induces AVP release in both regions, and the AVP release is calcium dependent. Acetylcholine-induced AVP release is antagonized by atropine or meca-mylamine, indicating that both muscarinic and nicotinic receptors are mediating the cholinergic effect in these brain regions. IL-1β (100 U/ml) had no effect on the basal AVP release from the hypothalamus, but significantly potentiated the acetylcholine-induced AVP release, lowering the threshold from 500 to 100 nM. This effect was completely blocked in the presence of neutralizing antibodies to IL-1β, atropine (10 µM) or mecamylamine (10 µM). IL-6, like IL-1β, also potentiated acetylcholine-induced AVP release, but to a lesser extent. Neither tumor necrosis factor-α nor interferon-γ had any effect on the basal or acetylcholine-induced AVP release from the hypothalamus. None of the cytokines tested had any effect on the basal or acetylcholine-induced AVP release from the amygdala. Our results suggest a hypothalamic site of action of IL-1β and IL-6 on the acetylcholine-induced AVP release. The stimulatory effects of IL-1 and IL-6 on adrenocorticotropin release have been ascribed to an increased release of corticotropin-releasing factor (CRF). These data further suggest that, in addition to CRF, AVP plays a role in the bidirectional communication between neuroendocrine and immune systems. Understanding the mode of interaction between IL-lβ and IL-6 with AVP could clarify pathophysiologic or toxic effects of high brain levels of these

ISSN:0028-3835    

DOI:10.1159/000126661

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Cysteamine (CSH), a sulfhydryl agent that promotes disulfide-exchange reactions, was studied for its effects on the immunoreactive (IR) levels and synthesis of oxytocin and vasopressin in the hypothalamus. CSH injection (300 mg/ kg s.c.) caused a rapid (1 h) suppression of 35S-cysteine incorporation into hypothalamic arginine vasopressin (VP) and oxytocin (OT). The reduction in labeling persisted for about 8 h; label incorporation was normal within 10 h of CSH administration. The drug did not influence 35S-cysteine incorporation into acid-precipitable protein, nor did it influence 35S-cysteine specific activity in the hypothalamus. In addition, 35S-VP and 35S-OT molecules could not be recovered from hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing and then reoxidizing conditions. Despite the reduction in peptide labeling, CSH treatment produced no alterations in the IR VP and OT contents of hypothalamus or posterior pituitary. These results indicate that CSH causes a true suppression of both VP and OT formation in hypothalamus, and suggest that the effect is either too transient to promote a reduction in endogenous stores of either peptide, or that the drug equally inhibits peptide production and removal (i.e., axonal transport, secretion).

ISSN:0028-3835    

DOI:10.1159/000126662

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To characterize the effect of androgens on the hypothalamo-pituitary-adrenal (HPA) axis we examined the regulation of corticotropin-releasing hormone (CRH) following gonadectomy and hormone replacement. Three-month-old male Fischer 344 (F344) rats were gonadectomized (GDX) or sham GDX. Control animals remained intact. Animals were sacrificed 1, 4, 7, 10, or 21 days following surgery. GDX rats had significantly elevated (p < 0.05) levels of hypothalamic CRH 21 days after surgery compared to intact and sham-operated rats. In a second study, 3-month-old male F344 rats were GDX and treated with the non-aromatizable androgen, dihydrotestosterone (DHT), using a Silastic capsule containing crystalline DHT propionate subcutaneously implanted in each animal’s back. Control animals were GDX and sham-treated or left intact (INT). Three weeks following gonadectomy, CRH levels in the hypothalamus of GDX rats showed a significant increase (p < 0.05) compared to intact animals. DHT treatment, beginning at the time of gonadectomy prevented this increase. CRH or arginine vasopressin (AVP) immunoreactivity was examined using immunocytochemistry. The number of CRH-immunoreactive (IR) cells in the paraventricular nucleus (PVN) of GDX, DHT-treated animals was significantly decreased (p < 0.05) compared to GDX rats. No differences were seen between treatment groups in CRH-IR cell numbers in the bed nucleus of the stria terminalis or the central amygdaloid nucleus or in AVP-IR cell numbers in the PVN. These data demonstrate that long-term castration increases hypothalamic CRH content and CRH-IR cell numbers in the PVN by removal of an androgen-dependent repressio

ISSN:0028-3835    

DOI:10.1159/000126663

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The present study was designed to investigate the time course of alterations in β1- and β2-adrenoceptor subtypes, α2-adrenoceptors and uptake sites for norepinephrine in the rat brain following thyroidectomy (TXT) and thyroxine replacement. The results indicate that alterations in the thyroid state lead to changes in the pre- and postsynaptic noradrenergic system that are both region- and receptor-specific. TXT caused the binding of 125-iodopindolol to β1-adrenoceptors to decrease in the cortex and hippocampus and caused its binding to β2-adrenoceptors to decrease in the hypothalamus. TXT caused 3H-idazoxan binding to α2-adrenoceptors to be reduced specifically in the amygdala. Following TXT, the binding of 3H-nisoxetine to norepinephrine uptake sites was found to be increased in the hippocampus and decreased in the hypothalamus. In most brain regions, thyroxine replacement for 7 or 28 days caused radioligand binding to recover to control levels. Thus it appears that a neuromodulatory link between thyroid hormone and the noradrenergic system exists in many regions of the rat

ISSN:0028-3835    

DOI:10.1159/000126664

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Quantitative autoradiography was used to assess alterations in serotonin (5-HT) receptor binding in the hypothalamus and hippocampus following denervation with 5, 7-dihydroxytryptamine (5, 7-DHT), ovariectomy (OVX) and gonadal steroid manipulation. Seven days after 5, 7-DHT injection, 5-HT1a receptor density was significantly increased in the ventromedial hypothalamic nucleus (VMN) of intact but not OVX femaled rats. Under these conditions 5-HT1b receptor density was unchanged in any brain region examined and 5-HT transporter binding was decreased in all 5, 7-DHT injected animals. In addition, there was a significant interaction between OVX and 5, 7-DHT for both the 5-HT1a receptor and the 5-HT transporter in the VMN, such that OVX inhibited the 5, 7-DHT-induced increase in 5-HT1a receptors and attenuated the 5, 7-DHT-induced decrease in 5-HT transporter binding. In a separate experiment the effect of gonadal steroid manipulation on 5-HT receptor binding was assessed. In female OVX rats, 5-HT1a receptor density was unchanged by estrogen or estrogen and progesterone administration. In male rats, castration significantly decreased 5-HT1a receptor density in the medial preoptic area. Estrogen and progesterone administration to female OVX rats increased the density of 5-HT1b receptors in the VMN, as compared to estrogen alone. The relationship of these results to the role of 5-HT in mediating lordosis behavior is discussed.

ISSN:0028-3835    

DOI:10.1159/000126665

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Hypothalamic growth hormone-releasing hormone (GHRH) and somatotropin release-inhibiting factor or somatostatin (SS) immunoreactive (ir) neurons were localized in pigs (n = 8) and cattle (n = 7) to identify neuroanatomical sites involved in the regulation of growth hormone secretion. Coronal and sagittal frozen sections (30–60 µm) of Zamboni’s fixed hypothalamic tissue, without prior colchicine treatment were incubated with GHRH or SS primary antisera for 48 h, then visualized by peroxidase-diaminobenzidine immunocytochemistry. Fusiform, bipolar SS-ir perikarya were located about the third ventricle in the periventricular nucleus, extending from rostral aspects of preoptic periventricular nucleus to a level approximate with caudal regions of the paraventricular nucleus. Rounded or fusiform, bipolar GHRH-ir perikarya were mostly located in ventrolateral portions of the arcuate nucleus in pigs and cattle, and within ventral aspects of the ventromedial nucleus in pigs but rarely in cattle. In both pigs and cattle, SS-ir and GHRH-ir fibers projected ventrally into the median eminence with dense and overlapping innervation of the external layer, especially dense in lateral regions. In pigs, but not as distinguishable in cattle, SS-ir fibers also densely innervated the ventromedial and arcuate hypothalamic nuclei. Double immunostained sections revealed close apposition of SS-ir fibers and varicosities with GHRH-ir perikarya in arcuate and ventromedial nuclei, and apposition of SS-ir and GHRH-ir varicosities in the median emin

ISSN:0028-3835    

DOI:10.1159/000126666

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The participation of adenohypophyseal estradiol receptors in the reinstatement of ovulatory cycles after lactation interruption was investigated. In rats whose pups were removed on day 13 postpartum (LRX), prolactin levels fell as from 1600 h on the same day, estradiol peaked on the morning of day 15 and gonadotropins and prolactin (PRL) surged on the afternoon of day 15. No significant changes in gonadotropins or estradiol levels were observed in rats which remained with their litters (LRP); in these rats daily afternoon surges of PRL were detected. No significant variations in anterior pituitary nuclear or cytosolic estradiol receptors were determined in LRP rats. In the nuclear fraction of LRX rats, an important increase (430.8 ± 124.9%) in receptor titers was observed on day 15. In these animals a significant increase (34.8 ± 1.3%) in cytosolic estradiol receptors was observed on day 14, followed by a fall on day 15 (–31.6 ± 6.6%) in comparison to day 13 levels. The receptor variations observed on day 15 closely resemble estrous cyclic changes determined in adult females. However, an observation which does not resemble those cycle variations is the increase in cytosolic receptors observed on day 14 in LRX rats. This increase may be the consequence of a decrease in dopamine levels induced by pup removal. To our knowledge this is the first time that the involvement of pituitary estradiol receptors in the reinstatement of ovulatory cycles after lactation interruption has been descr

ISSN:0028-3835    

DOI:10.1159/000126667

出版商:S. Karger AG    

年代:1994

数据来源: Karger