ISSN:0028-3835    

DOI:10.1159/000127211

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Supraphysiological doses of glucocorticoids inhibit growth hormone (GH) secretion in man and experimental animals. We investigated whether glucocorticoids inhibit GH secretion through changes in the gene expression of GH, hypothalamic somatostatin (SS) and GH-releasing hormone (GHRH), and whether such changes vary with the dose and duration of glucocorticoid excess. Male rats, 6 weeks of age, were treated with injections of either saline or different doses of dexamethasone (40, 200, 500 or 1,000 µg/kg/day) intraperitoneally for 3 or 8 days. Total RNA extracted from the anterior pituitary and hypothalamus was analyzed by Northern blot hybridization. SS mRNA level was also assessed in smaller hypothalamic fragments containing predominantly the periventricular and paraventricular nuclei, and by in situ hybridization. A biphasic effect on SS mRNA levels was observed such that a significant increase (p < 0.001) was demonstrated in the periventricular nucleus after 3 days of dexamethasone 1,000 µg/kg/day, but a reduction in hypothalamic SS mRNA was seen after 8 days for all doses employed (p < 0.05 or p 200 µg/kg/day (p < 0.05). Pituitary GH mRNA levels were increased after 3 days at doses ≧500 µg/kg/day (p < 0.05) but showed no significant change at all doses after 8 days.We conclude that glucocorticoid excess is associated with changes in the gene expression of GH, hypothalamic SS and GHRH, which vary with the dose and duration of glucocorticoid treatment. Glucocorticoids inhibit GH secretion in vivo through a reduction in hypothalamic GHRH gene expression and, in animals with shorter duration of glucocorticoid excess, also through an increase in SS gene expression in the periventricular nu

ISSN:0028-3835    

DOI:10.1159/000127212

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

To determine whether an acute withdrawal of growth hormone (GH) alters sleep, the effects of antiserum to GH (GH-AS) on sleep were studied in the rat. Sleep-wake activity and cortical brain temperature (Tc) were recorded for 2 days after systemic injection of physiological saline. Then, one group of rats (n = 6) received GH-AS whereas another group of rats was injected with normal rabbit serum (n = 6). The injections were given 1 h before light onset, and the rats’ behaviors were recorded for 23 h during the subsequent 12-hour light and 12-hour dark period. Sleep and Tc were not altered after normal rabbit serum. The durations of both rapid eye movement sleep (REMS) and non-REMS (NREMS), and the EEG slow-wave activity during NREMS were significantly suppressed during the light period following the injection of GH-AS. Tc tended to decrease for 3 h and a small rise was observed thereafter during the light period, but these changes were not statistically significant. The assay of GH in plasma samples obtained at 30-min intervals for 5 h after injection of normal rabbit serum or GH-AS verified the decreases in plasma GH concentrations in response to GH-AS. It is suggested that GH may promote sleep possibly via some metabolic action

ISSN:0028-3835    

DOI:10.1159/000127213

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The expression of insulin-like growth factor binding protein-2 (IGFBP-2) during postnatal development of the rat neurointermediate pituitary was characterized using immunocytochemistry and in situ hybridization. Glial cells in the neural lobe (NL) showed robust expression of IGFBP-2 throughout the postnatal period and continuing into adulthood. These were identified as pituicytes by the presence of S-100 protein; IGFBP-2 was not present in microglia in the NL. IGFBP-2 immunoreactivity was more punctate in mature pituicytes, suggesting a possible association with the cell membrane. No expression of IGFBP-2 by brain astrocytes was observed at any age examined, even in regions such as the median eminence and subfornical organ that lack a blood-brain barrier. IGFBP-2 was also localized immunocytochemical-ly in melanotropes and glial-like cells of the intermediate lobe (IL). Positive cells were most numerous in neonates and declined thereafter, with immunoreactivity undetectable by 65 days of age. IGFBP-2 mRNA was detected in the IL only at 1 day of age. These findings are consistent with a potential role for IGFBP-2 in modulating effects of the insulin-like growth factors during development of the neurointermediate lobe. The constitutive expression of high levels of IGFBP-2 by mature pituicytes also suggests that this protein could be secreted and/or influence a variety of processes in the mature NL, such as glial proliferation, axonal growth, or morphological plasticity of pituicytes.

ISSN:0028-3835    

DOI:10.1159/000127214

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0028-3835    

DOI:10.1159/000127215

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Substance P (SP) and estrogen receptor immunoreactivity overlap in the mid-brain central gray (MCG) of female guinea pigs. Estrogen-receptor-containing cells are found throughout the rostrocaudal extent of the MCG. Moderately dense SP immunostaining is also found in this region. SP-immunoreactive punctate structures suggestive of boutons were found in close association with the processes of some estrogen-receptor-immunoreactive neurons. These associations were observed primarily in the lateral and ventrolateral MCG at the midcollicular and caudal levels. This finding suggests an anatomical substrate for interactions between SP and estradiol-sensitive neurons in the midbrain. Such interactions may underlie the effects of SP on female sexual behavior.

ISSN:0028-3835    

DOI:10.1159/000127216

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Relaxin, administered parenterally, has been shown to increase the release of oxytocin (OT) into the circulation and increase the firing rate of OTergic neurons. The objective of the present study was to determine if relaxin administration can result in the expression of a transcription factor, suggesting that it alters transcriptional activity within OTergic neurons at the level of the hypothalamus. Primigravid rats were ovariectomized and a jugular cannula was inserted on day 11 of gestation (g11). Pregnancy was maintained by implanting 17β-estradiol and progesterone caplets subcutaneously at the time of ovariectomy. At g19, rats were challenged with intravenous relaxin or isotonic saline and the brains were removed for study. Immunohistochemistry was performed on coronal brain sections, utilizing Fos as a marker of cellular activation. In the group receiving relaxin, Fos-like immunoreactivity (Fos-IR) was abundant only in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, as well as in the subfornical organ (SFO). In contrast, Fos-IR in the group given isotonic saline was lacking in these three brain regions. A double label study using antibodies against Fos and OT demonstrated that a majority of the Fos-labeled cells in the hypothalamus were OTergic. Because Fos can act as a transcription factor, we interpret these data to indicate that transcription within OTergic cells is altered following relaxin administration, with abundant Fos-IR being limited to the SON and PVN of the hypothalamus and the SFO during late pregnancy in the rat

ISSN:0028-3835    

DOI:10.1159/000127217

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The aim of the present study was to assess potential brain sites of stimulation by peripheral interleukin (IL)-6 of the hypothalamo-pituitary-adrenal (HPA) axis in the rat, using c-fos protein as a marker of cellular activation. Involvement of prostaglandins in IL-6-induced ACTH secretion and c-fos expression was also investigated. IL-6 was infused continuously (40 ng/min) for 90 min to conscious male rats. Blood samples were taken before the infusion and at 30 and 90 min for measurement of plasma ACTH. Expression of c-fos in the brain was examined by immunohistochemistry. Administration of IL-6 significantly elevated plasma ACTH levels at 30 min (495 ± 105 vs. 117 ± 17 pg/ml in controls, p < 0.05). Elevated levels were still present at 90 min (596 ± 139 vs. 113 ± 20 pg/ml in controls, p < 0.05). Infusion of IL-6 (3.6 µg/rat) markedly triggered c-fos expression in hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), as well as in the central amygdaloid nucleus (CeA), the nucleus tractus solitarius and the locus coeruleus. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg, i.v.) suppressed the ACTH response induced by IL-6. The number of IL-6-induced immunoreactive cells in the PVN was significantly reduced by indomethacin pretreatment (p < 0.01), but the number of IL-6-induced c-fos-positive cells in the SON and CeA remained unchanged. These findings suggest that circulating IL-6 may exert central actions by acting directly or indirectly on brain neurons. In addition, the ability of IL-6 to activate the HPA axis may depend upon the release of prostaglandins, probably in the b

ISSN:0028-3835    

DOI:10.1159/000127218

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL·6 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 µg/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-µg/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-µg/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 µg/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 µg/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermoge

ISSN:0028-3835    

DOI:10.1159/000127219

出版商:S. Karger AG    

年代:1997

数据来源: Karger