摘要:

We previously reported a reduction of glucocorticoid receptors (GCR) in diethylstilbestrol-induced pituitary tumors (DES-T) in rats. Presently, we found that bromocriptine (BROM) treatment increased the levels of GCR in DES-T, demonstrated by steroid binding assays and immunocytochemistry using a monoclonal antibody against the type II GCR. We also found that the high content of nuclear estradiol receptors in the adenomata and the elevated levels of PRL in serum of DES-T were significantly reduced after BROM treatment. In parallel studies, PRL secretion was measured after administration of ether stress. In controls, serum PRL markedly increased after ether and this effect was blunted by prior dexamethasone (DEX) administration, due to the steroid negative feedback on PRL secretion. In animals with DES-T, ether stress had no effect on serum PRL, and the inhibition by DEX was lost unless they received BROM, which restored the negative feedback of DEX on serum PRL. Although increases of PRL titers in pituitary tumors may be due to estrogenic stimulation of lactotroph proliferation and function, coupled to absent dopaminergic inhibition on these cells, other mechanisms are possible. In this respect, inefficient steroid negative feedback on PRL synthesis due to down-regulation of GCR may contribute to hyperprolactinemia. This mechanism is supported from the restoration of GCR and steroid negative feedback on serum PRL by treatment of tumor-bearing rats with BROM.

ISSN:0028-3835    

DOI:10.1159/000126550

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effects of Δ9-tetrahydrocannabinol (THC) on the activity of brain dopaminergic neurons might be subject to gonadal influence. In this work, we tested this hypothesis in relation to the effects of THC on tuberoinfundibular dopaminergic (TIDA) activity, the anterior pituitary sensitivity to dopamine (DA) and prolactin (PRL) secretion. To this end, we examined the effects of an acute dose of this cannabinoid administered during different phases of the estrous cycle in the morning or afternoon. The results were as follows. THC, administered during the morning of estrus, stimulated TIDA activity as reflected by increases in DA and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents and tyrosine hydroxylase (TH) activity in the medial basal hypothalamus. This was accompanied by an increase in the responsiveness of the anterior pituitary to DA, as reflected by the increase in the density of D2 receptors and the corresponding decrease in PRL release. By contrast, plasma PRL levels increased when THC was administered on the afternoon of estrus, in parallel with a significant reduction in the number of D2 receptors in the anterior pituitary gland and no effects on TIDA activity. A similar decrease in the anterior pituitary density of D2 receptors, but with no changes in plasma PRL levels, was observed when THC was administered during the morning of diestrus. This effect was not accompanied by changes in TIDA activity either. The administration of THC during the aftenoon of diestrus stimulated TIDA activity (increases in DA and DOPAC contents and TH activity in the medial basal hypothalamus), as occurred when the cannabinoid was administered during the morning of estrus, but in this case, it decreased the density of D2 receptors in the anterior pituitary and did not modify plasma PRL levels. These results contrast with the absence of significant changes observed when THC was administered during the morning or the afternoon of proestrus, although the highest plasma PRL levels and TIDA activity were observed during the afternoon of this phase. In summary, the effects of THC on TIDA activity, the sensitivity of the anterior pituitary to DA and PRL release seem to be under gonadal influence. This can be concluded from the observations that THC treatment caused different effects when administered to rats at different stages of the ovarian cycle. The classical inhibitory effect of THC on PRL release via an enhancement of TIDA activity observed in males was observed in females only during the morning of estrus. Different effects were seen during the diestrus and the afternoon of estrus, whereas its administration during proestrus was ineffective

ISSN:0028-3835    

DOI:10.1159/000126551

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The purpose of the present study was to examine the effects of galanin on the basal and stimulated activity of tuberoinfundibular dopaminergic (TIDA) neurons in male and female rats. TIDA neuronal activity was estimated by measuring dopamine (DA) synthesis [accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor] and metabolism [ratio of 3,4-dihydroxyphenylacetic acid (DOPAC) to DA concentrations] in terminals of these neurons in the median eminence. Central administration of galanin (2 µg/rat, i.c.v.) produced a rapid (by 15 min) increase in plasma prolactin concentrations, but had no effect on the ratio of DOPAC to DA in the median eminence of either male or female rats. In contrast, galanin decreased the ratio of DOPAC to DA in the median eminence of both male and female rats whose TIDA neuronal activity was stimulated following administration of the DA antagonist haloperidol (1 mg/kg, s.c, 12 h). The galanin receptor antagonist galanin-(1–13)-bradykinin-(2-9)-amide had no effect on the accumulation of DOPA in the median eminence of male rats per se, but blocked the inhibitory effects of either exogenous or endogenous galanin on median eminence DOPA accumulation in haloperidol-treated rats. These results indicate that in both male and female rats, galanin-induced activation of prolactin secretion is not mediated by changes in tonic inhibition of hormone release by TIDA neurons, and that TIDA neurons are responsive to the inhibitory effects of galanin only under activated conditio

ISSN:0028-3835    

DOI:10.1159/000126552

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Previous studies have indicated that 30 min of swimming in room temperature water is a potent stimulus for the secretion of β-endorphin (βE) from the intermediate lobe (IL) of the pituitary in rodents. Repeated daily challenge with this paradigm over days to weeks leads to a progressive increase in proopiomelanocortin (POMC)-derived IL peptides and POMC mRNA levels as well as an increase in the stimulated secretion of βE in response to rechallenge with swim. The current studies were undertaken to examine the possible role of dopamine systems in mediating swim stress-induced changes in IL βE biosynthesis and release. Confirming previous results, a 30 min swim stress exposure caused plasma concentrations of βE to increase several fold. Apomorphine (APO), a dopaminergic agonist, completely blocked this effect, suggesting that dopamine receptors may mediate the acute IL response to swim stress. Animals that swam once daily for 14 days displayed elevated βE levels in both the IL and plasma 24 h after the last swim session. In these animals, repeated administration of APO did not reverse swim-stress-induced changes in βE. Immediately following an acute-swim rechallenge, animals which had been previously swim-stressed for 14 days demonstrated significantly greater βE release than naive animals. Again, an acute injection of APO inhibited the acute increase in IL secretion, suggesting that repeatedly swum animals are still responsive to the acute effects of APO even though repeated coadministration of APO with swim exposure had no effect on IL βE peptide stores or plasma βE concentration. In a final experiment, animals treated for 14 days with either daily swim stress or a maximally effective dose of haloperidol (a dopaminergic antagonist) displayed increased IL levels of POMC mRNA. Combined haloperidol and swim treatment had an additive effect on POMC mRNA levels, suggesting that swim stress might be acting via nondopaminergic mechanisms. Taken together, these studies indicate that chronic swim-stress-induced changes in IL βE biosynthesis and secretion may involve non-dopaminerg

ISSN:0028-3835    

DOI:10.1159/000126553

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Adrenalectomy is frequently used to deplete adrenocortical hormones in physiological and receptor-binding studies in animals. However, this procedure is irreversible, removes both the cortex and medulla, and produces many negative side effects such as hypotension and hypoglycemia. Aminoglutethimide is a steroid synthesis inhibitor which depletes adrenocortical hormones without these negative effects. However, aminoglutethimide itself has been shown to produce behavioral and physiological deficits. In the present experiments, dose-response relationships were determined for the effects of aminoglutethimide on corticosterone levels, motor coordination, and body temperature in C57 and DBA mice. Aminoglutethimide (5.4-54mg/kg) inhibited the increase in plasma corticosterone concentrations normally observed in response to restraint stress. Only at higher doses (170–1,000 mg/kg) were rotarod performance and body temperature affected. The corticosterone response to restraint stress recovered fully between 12 and 24 h after aminoglutethimide. In the present study, doses of aminoglutethimide were found that temporarily inhibit stressed corticosterone release without producing motor deficits and temperature decreases. These results indicate that aminoglutethimide is a potential substitute for adrenalectomy in studies on the effects of removal of adrenocortical hormone

ISSN:0028-3835    

DOI:10.1159/000126554

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Pregnancy and parturition are associated with opioid-mediated elevations in maternal pain thresholds. This analgesia is subserved by a spinal cord dynorphin/K-opiate receptor system. During gestation, elevated pain thresholds are paralleled by a significant increase in the content of dynorphin (1–17 and 1–8) in the lumbar spinal cord. An additional increment in lumbar dynorphin (1–17) concentration, but not that of dynorphin (1–8), occurs in parturient animals. Simulation of the pregnancy blood concentration profile of 17β-estradiol and progesterone (‘hormone-simulated pregnancy’) also results in an opioid analgesia, the magnitude and temporal pattern of which closely approximates that of actual gestation. The current study demonstrates that during hormone-simulated pregnancy, the spinal cord content of dynorphin (1–17) [but not dynorphin (1–8)] is positively modulated. This regulation is time- (or dose-)-dependent and region-specific. Significant elevations in spinal levels of dynorphin (1–17) are observed during steroid dose periods 3 and 4, corresponding to the last week of actual gestation and parturition, respectively. Increased dynorphin (1–17) content is observed in only the lumbar spinal region. These changes are temporally and anatomically identical to those which occur during actual gestation and parturition. It is concluded that changes in circulating 17β-estradiol and progesterone, that occur as a natural consequence of gestation, activate a dynorphin system in the lumbar spinal cord. This attenuates the pain associated with late pregnancy and labor. The pattern of circulating sex steroids can be an important determinant of the activity of central opi

ISSN:0028-3835    

DOI:10.1159/000126555

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Estrogen receptors were visualized in adult ferret brains using the H222 estrogen receptor antibody and immunocytochemical techniques. H222 immunoreactive (H222ir) cell nuclei were present in many forebrain regions in gonadectomized ferrets of both sexes. In many instances, H222ir cells also had immunoreaction product in their processes. All cells with H222ir processes also contained H222ir nuclei. More H222ir processes were observed in females in the medial and lateral preoptic area/anterior hypothalamus, and at the level of the descending fornix and caudal anterior commissure. Quantitative image analysis confirmed that females had significantly more (approximately 50%) extranuclear H222 immunoreaction product than males in cells in the magnocellular or preoptic subnuclei of the bed nucleus of the stria terminalis. Cells in the principal subnucleus of the bed nucleus of the stria terminalis and ventrolateral septum were notable for the relative paucity of H222ir processes. Sex differences in the intracellular extranuclear distribution of estrogen receptor protein in particular brain regions might contribute to the differential regulation of estrogen-dependent functions in the two sexes.

ISSN:0028-3835    

DOI:10.1159/000126556

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Glucocorticoid excess inhibits somatic growth in man and laboratory animals. While the mechanism involved is likely to be multifactorial, indirect evidence suggesting the role of an enhanced endogenous somatostatin (SS) tone has been reported. However, there has been no direct evidence indicating an increased synthesis or secretion of hypothalamic SS. In this study, we investigated the effects of glucocorticoids on hypothalamic SS expression by measuring the peptide and mRNA content of SS in whole hypothalamic blocks of male Sprague-Dawley rats sacrificed 4 weeks after adrenalectomy or sham operation. Adrenalectomy decreased the SS content in the rat hypothalamus (p < 0.05), an effect which was reversed by dexamethasone treatment for 10 days. On the other hand, total hypothalamic SS mRNA levels were unaffected by adrenalectomy, but became significantly decreased following dexamethasone treatment (p < 0.05). Using in situ hybridization, this reduction in SS gene expression was shown to occur consistently in the periventricular nucleus and in the parvocellular subdivision of the paraventricular nucleus. The effects of adrenalectomy and dexamethasone on SS mRNA levels were further quantitated in hypothalamic fragments containing predominantly the periventricular and paraventricular nuclei. Somatostatin mRNA levels in these tissue fragments were marginally increased by adrenalectomy (p < 0.05), but showed a 50% reduction following dexamethasone treatment (p < 0.0001). In conclusion, our findings suggest that the inhibitory effect of glucocorticoids on somatic growth is probably not mediated via an effect on hypothalamic SS gene expression.

ISSN:0028-3835    

DOI:10.1159/000126557

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The secretion of growth hormone (GH) is impaired in the genetically obese Zucker rat where GH gene expression and plasma GH levels are depressed; however, the underlying mechanism of this abnormality remains unclear. We have evaluated the potential causative role of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) gene expression in the onset of the decreased GH mRNA levels by studying both GHRH and SRIH mRNA and peptide levels in obese and lean rats at 5 weeks of age when the decrease in GH mRNA is first detected. At that age both GHRH content and GHRH mRNA were significantly reduced in obese rats as compared to lean controls; hypothalamic SRIH content was also decreased in obese rats, but SRIH mRNA levels did not differ. Since GHRH is capable of stimulating GH gene expression, the decreased GHRH mRNA level could be a critical factor in causing the attenuation in GH gene expression and consequent diminution of circulating plasma GH.

ISSN:0028-3835    

DOI:10.1159/000126558

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

It is well-established that the activity of the endocrine thymus is under neuroendocrine control. In particular, growth hormone (GH) and thyroxine (T4) have been shown to be capable of reconstituting thymus function in hormone-deficient animals. It was therefore of interest to assess the effect of combined administration of ovine GH (0.1 mg/100 g BW/day) and T4 (10 µg/100 g BW/ day) on serum thymulin levels in young (5 months), old (21 months) and senescent (29-30 months) male Sprague-Dawley rats. Age-matched controls received 0.1 mg bovine serum albumin/100 g BW daily during the same period (14 days). Prolactin (Prl), GH, T4 and triiodothyronine (T3) were measured in serum by radioimmunoassay, whereas serum thymulin was determined by rosette bioassay. As expected, GH and T4 were lower in the old and senescent controls whereas serum Prl displayed a slight age-related increase. No age changes were detected in serum T3. Hormone-treated animals showed supra-physiologic levels of both T4 and T3, but serum levels were comparable among the three treated age groups for each thyroid hormone. Endogenous GH levels were moderately elevated in the treated rats. In the control rats serum thymulin showed a marked reduction from 5 to 21 months of age but no further reduction was observed between 21 and 29-30 months. Hormone treatment induced a mean relative increase (% increase relative to age-matched controls) in serum thymulin of 44, 38 and 48% in young, old and senescent rats, respectively. Despite this stimulation, thymulin levels in the old and senescent treated groups were still significantly lower than the corresponding values in the young controls. It is concluded that (a) the activity of the endocrine thymus declines with age in male rats, and (b) in relative terms, aged rats possess a preserved capacity to increase thymulin secretion in response to combined administration of GH and T4

ISSN:0028-3835    

DOI:10.1159/000126559

出版商:S. Karger AG    

年代:1993

数据来源: Karger