摘要:

The pituitary and hypothalamic content of dynorphin was determined by radioimmunoassay and characterized by high-performance liquid chromatography (HPLC) in adult female Sprague-Dawley rats, intact and ovariectomized with and without estrogen treatment. Animals were given estradiol benzoate, or vehicle (oil) by six daily intramuscular injections. Anterior pituitary content of immunoreactive (ir)-dynorphin in ovariectomized rats was approximately twice that of intact animals, and consisted of a single HPLC peak co-eluting with dynorphin 32. Administration of estradiol benzoate (0.06–6 µg/day) caused a marked decrease of ir-dynorphin in the anterior lobe of castrate female rats, with a half-maximal effect at 0.2 µg/day; levels were restored to those seen in intact animals with 6 µg estradiol benzoate per day, an effect which was not influenced by concomitant administration of progesterone (1 mg/day), or bromocriptine (100 µg/day). In the hypothalamus and neuro-intermediate lobe multiple peaks of immunoreactive dynorphin were seen, coeluting with dynorphin A 1–8, dynorphin A 1–17 and dynorphin 32. Neither castration nor estrogen treatment altered ir-dynorphin content in these tissues. These findings suggest that the ovary exerts a specific modulating influence on AP ir-dynorphin in the rat, and that in addition this inhibition appears to be mediated by ovarian

ISSN:0028-3835    

DOI:10.1159/000124882

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The influence of adrenalectomy and corticosterone substitution was investigated on Leu-Phe cleaving endopeptidase activity and on the levels of γ-endorphin and β-endorphin in the pituitary gland and the brain. The enzyme activity was quantitated by a specific radiometric assay based on the cleavage of the Leu17-Phe18 bond in a NH2 and COOH-terminally protected synthetic substrate wich was analogous to β-endorphin-(15–19). This activity may mimick the formation of γ-endorphin. β-Endorphin and γ-endorphin were measured by specific radioimmunoassays. After 14 days of adrenalectomy enzyme activity had increased in anterior (15%) and neurointermediate lobes of the pituitary gland (30%), hypothalamus (25%), and liver (15%). This increase was prevented when the adrenalectomized animals were subjected to chronic corticosterone substitution by subcutaneous implantation of a pellet of 100 mg. Extirpation of only the adrenal medulla did not affect the Leu-Phe cleaving activity. Enzyme activity in the septum, hippocampus, and cerebellum had not changed after adrenalectomy. Determination of immunoreactive levels of γ- and β-endorphins showed that in the anterior pituitary gland γ- and β-endorphins had increased by 275 and 300%, respectively, 14 days after adrenalectomy. No significant changes were observed in endorphin levels of the intermediate lobe of the pituitary gland, hypothalamus, hippocampus, and septum. The results indicate that Leu-Phe cleaving endopeptidase activity is sensitive to glucocorticoids in tissues containing proopiomelanocortin-producing cells, i.e., anterior and neurointermediate pituitary gland and the hypothalamus. In the anterior pituitary gland it is correlated with the levels of γ- and

ISSN:0028-3835    

DOI:10.1159/000124883

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Frontal, dorsal, or sham deafferentations were placed at various locations within the hypothalamus in order to study the neural pathways involved in pseudopregnancy (PSP), estrous cyclicity, and prolactin (PRL) secretion in the rat. Dorsal or sham transections did not interfere with PSP or estrous cyclicity. Frontal cuts placed on day 3–4 of PSP between the posterior border of the optic chiasm and the anterior tip of the mediobasal hypothalamus (MBH) led to interruption of diestrus within 3–5 days. With frontal cuts placed more caudally in the MBH, and with frontal cuts placed rostrally at the anterochiasmatic area, the duration of PSP was within a normal range. Irrespective of their effects on PSP, anterochiasmatic and retrochiasmatic cuts were associated with onset of persistent estrus, and MBH transections resulted in either persistent estrus in some rats or regular estrous cycles in the others. In deafferentated rats that showed persistent estrus, the basal plasma concentrations of PRL measured 3–4 weeks after ovariectomy were 2- to 3-fold higher than in deafferentated and sham-deafferentated animals that were cyclic before ovariectomy. Electrical vaginocervical stimulation induced secretion of nocturnal PRL surges in long-term ovariectomized rats with dorsal or sham transections, but not in those bearing frontal cuts, regardless of the neuroanatomical location of the frontal cut. These results suggest that (1) impulses generated at the uterine cervix must reach the medial preoptic area, a putative ‘anti-surge center’, and proceed from there to the MBH, in order to allow initiation of nocturnal PRL release; (2) the ‘surge center’ that transmits the nightly signal for PRL release is located above the optic chiasm and projects caudally to the MBH, and (3) preoptic-hypothalamic pathways controlling PSP and nocturnal PRL surges are dissociated from gonadotropin-releasing hor

ISSN:0028-3835    

DOI:10.1159/000124884

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Perikarya and terminals of tuberoinfundibular dopaminergic (TIDA) neurons are located in the arcuate nucleus (ARN) and in the median eminence (ME), respectively. Dopamine (DA) released from TIDA terminals in the ME inhibits prolactin secretion from the anterior pituitary. Anatomical studies have described the sources of afferents to ARN and ME, but not to TIDA neurons per se. The ventromedial nucleus (VMN) and the dorsomedial nucleus (DMN) of the hypothalamus project to ARN and ME and have a role in prolactin regulation. In the present study, VMN and DMN were investigated as possible sources of TIDA afferents. Alterations in the activity of TIDA neurons were estimated by measuring plasma concentrations of prolactin and the rates of DA synthesis (3,4-dihydroxyphenylalanine – DOPA – accumulation after administration of the decarboxylase inhibitor NSD 1015) and metabolism (concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid – DOPAC) in the ME following electrical stimulation of ARN, VMN, and DMN in ova-riectomized female rats. Thirty minutes of bilateral stimulation of ARN or DMN increased DOPA accumulation in the ME; stimulation of the VMN had no effect. 5-Hydroxytryptamine synthesis in the ME was unaffected by stimulation of any region. Plasma prolactin levels declined during DMN stimulation, varying with the frequency and duration of the electrical stimulus. DA metabolism within TIDA neurons increased with DMN stimulation, as evidenced by increased DOPAC concentrations in the ME. In females whose basal TIDA activity has been increased by haloperidol treatment or decreased by bromocriptine treatment, DMN stimulation was still able to increase DOPA accumulation in the ME. The present data suggest the presence of stimulatory TIDA afferents originating from or passing through th

ISSN:0028-3835    

DOI:10.1159/000124885

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Vasoactive intestinal peptide (VIP) gene transcripts were demonstrated by RNA blot hybridization using VIP-specific RNA hybridization probes. High levels of expression were observed as early as in 16-day-old embryos. In aging rats, the VIP-mRNA levels were reduced significantly (in the cerebral cortex) as compared to 21-day-old rats. Our results suggest a role for the VIP gene protein products during embryonal development. During aging processes the decrease in VIP gene transcripts may be a consequence of either a reduction in the transcriptional activity of VIP neurons or death of VIP-producing cells.

ISSN:0028-3835    

DOI:10.1159/000124886

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The concentration of mRNA encoding proopiomelanocortin (POMC) was measured in AtT-20/D-16v cells, a clonal pituitary tumor cell line. Treatment of the cells with potassium (20 mM) or veratridine (10 µM) for 12, 24 and 48 h caused a time-dependent increase in the levels of POMC mRNA which became significant after 24 h. These effects were not seen in the presence of the sodium channel blocker tetrodotoxin (5 µM). In addition, the calcium channel blocker verapamil (10 µM) completely abolished the responses to either potassium or veratridine, whereas the calcium channel agonist Bay K 8644 (0.1µM) potentiated the effect of potassium. Furthermore, the calcium channel blockers verapamil (10 µM) and nidefipine (1 µM) significantly decreased not only basal levels of POMC mRNA but also the increase of mRNA levels induced by corticotropin-releasing factor (CRF; 0.1 µM), 8-bromo-cAMP (1 mM) or cholera toxin (100 ng/ml). The drug-induced alterations in the mRNA POMC levels of the cells were, in each case, associated with similar alterations of immunoreactive β-endorphin in the medium. These results indicate that membrane depolarization to activate sodium channels and calcium channels initiates an entry of calcium ions which triggers POMC gene expression in the AtT-20 cells. Moreover, calcium entry into the cells may exert a tonic stimulatory effect on POMC mRNA under basal conditions and may also contribute to the enhancing effect of CRF or cAMP on POMC mRNA in thes

ISSN:0028-3835    

DOI:10.1159/000124887

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The effectiveness of thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) to release prolactin (PRL) after a brief interruption of the tonic inhibitory action of dopamine (DA) was investigated in enzymatically dispersed anterior pituitary cells in superfusion. We also studied the involvement of cAMP and Ca2 + /protein kinase C second messenger systems in the mediation of the stimulated PRL release. Anterior pituitary cells from lactating or E2-treated rats were superfused for 10 min with secretagogues either during continual dopamine administration or 10–20 min after a 10-min transient interruption of DA (500 nM). Removal of DA for 10 min resulted in a significant increase in PRL release which had returned to basal levels 10 min after the return of DA to the superfusion. During continuous DA exposure, TRH administration (10 nM) did not alter the rate of PRL release from cells from lactating rats; however, TRH caused a 2-fold increase after the transient interruption of DA. The transient escape from DA inhibition also increased the effectiveness of TRH (100 nM) to release PRL from cells from E2-treated rats (from a 4- to a 15-fold stimulation). In contrast, VIP (0.5 or 5 µM) caused a 2-fold stimulation of PRL release in both cells treated with continuous or transiently interrupted DA. The transient removal of DA also potentiated PRL release induced by treatment with the Ca2 + ionophore A23187 (5 and 20 µM) and/or the protein kinase C stimulator 12–0-tetradecanoyl-phorbol-3-acetate (TPA) (50 nM), but not following treatment with the adenylate cyclase activator forskolin (10 µM) or the cAMP analog 8-Br-cAMP (2.5 mM). These data suggest that a transient escape from DA inhibition increases the responsiveness of lactotrophs to the PRL-re-leasing action of TRH but not to VIP. It appears that the potentiated action of TRH involves a Ca2 + /protein kinase C-mediated p

ISSN:0028-3835    

DOI:10.1159/000124888

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In humans, corticoids suppress growth hormone (GH) secretion elicited by a variety of stimuli, while in vitro they potentiate GH release. To further study this problem, the effect of two doses of dexamethasone on GH secretion elicited by GH-releasing hormone (GHRH) in 6 normal volunteers was studied. Each subject underwent three tests, on 3 separate days with GHRH 1–29 (1 µg/kg i.v. at 12.00 h). On the control day, only GHRH was given, on the second day dexamethasone 4 mg i.v. was administered at 09.00 h (3 h before GHRH) and on the third day dexamethasone 8 mg p.o. was given 12 h before GHRH (at 00.00 h). The GHRH-induced GH peak was 9.9 ± 2.0 ng/ml, while 4 mg dexamethasone significantly (p < 0.05) potentiated GH secretion elicited by GHRH (29.2 + 5.7 ng/ml). When dexamethasone 8 mg was given 12 h before, GHRH-induced GH secretion was completely blocked (3.0 + 1.1 ng/ml) (p < 0.05). These results indicate that corticoids have two different actions: an acute potentiating activity on GHRH, and a delayed blocking action on GHRH-induced GH secret

ISSN:0028-3835    

DOI:10.1159/000124889

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Although it has been suggested pro-opiomelancortin (POMC)-related peptides widely distributed throughout brain may be neurotransmitters or neuromodulators, little is known about their secretion from neurons because it is difficult to study neurosecretion in vivo. Previous work has shown that POMC-related peptides in hypothalamus may be released in response to potassium-induced depolarization. However, little attention has been directed toward studying secretion of POMC-related peptides in extrahypothalamic brain. To demonstrate the possibility that POMC peptides in extrahypothalamic brain may also be neuroregulators and can be released in response to a specific stimulus, the release of derivatives of POMC, immunoreactive (IR) adrenocorticotropic hormone (ACTH) and IR-β-endorphin, from dissociated amygdala and cortical brain cells was studied in response to potassium-induced depolarization. Depolarizing concentrations of potassium in the presence of calcium stimulated significant increments in release of IR-ACTH/IR-β-endorphin by amygdala (111/105%) and cortical (162/136%) cells. Stimulated release occurred following an experimental paradigm used to stimulate release of classical neurotransmitters and neuropeptides and suggested POMC-related peptides could be neuroregulators in extrahypothalamic brai

ISSN:0028-3835    

DOI:10.1159/000124890

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Recently, it was shown that a 1.5-ml subcutaneous saline injection depressed N-acetyltransferase (NAT) activity and melatonin content in the rat pineal gland at night. The present studies were undertaken to determine if another perturbation, swimming, could duplicate this response. Rats swam at 23.10 h (lights out at 20.00 h) for 10 min and were killed 15 and 30 min after the unset of swimming. Pineal NAT activity was found to be unaffected while melatonin content was depressed dramatically. Hydroxyindole-O-methyltransferase (HIOMT) activity as well as the content of serotonin (5HT), 5-hydroxytryptophan (5HTP) and 5-hydroxyindoleacetic acid (5HIAA) were not changed by this treatment. In a second study, pineal melatonin again was depressed without a concomitant drop in NAT activity. Mean serum melatonin at 15 min after onset of swimming was increased although the rise was not statistically significant. In the final study, it was found that NAT activity was slightly increased in intact rats and unchanged in adrenalectomized rats at 7 min after swimming onset. At 15 min both intact and adrenalectomized animals had NAT activity values similar to those of controls. Pineal melatonin content in intact and adrenalectomized rats plummeted to 50% of control values at 7 min and fell further to 25% at 15 min. While the rate of melatonin synthesis was not directly measured, lack of change in the activities of the enzymes involved in melatonin synthesis and the contents of two melatonin precursors suggests that swimming depresses pineal melatonin content by enhancing melatonin efflux from the gland.

ISSN:0028-3835    

DOI:10.1159/000124891

出版商:S. Karger AG    

年代:1988

数据来源: Karger