摘要:

Administrations of the glucocorticoid receptor antagonist (anti-glucocorticoid, RU38486) and the mineralocorticoid antagonist (anti-mineralocorticoid, RU28318) followed by frequent, sequential blood sampling were employed to investigate the possible role the brain mineralocorticoid receptor (MR, type I) and glucocorticoid receptor (GR, type II) have in the regulation of basal and stress-induced adrenocortical secretion in the rat. The anti-mineralocorticoid and anti-glucocorticoid were administered subcutaneously (s.c.) at doses of 2.5 mg and 1.0 mg/100 g body weight, respectively. Both antagonists were also given intracerebro-ventricularly (i.c.v.) at a dose of 100 ng/rat. Under basal non-stressed conditions (at the diurnal trough in the morning), injections of either saline, anti-glucocorticoid (s.c. or i.c.v.) or anti-mineralocorticoid (s.c.) did not have effect on the plasma corticosterone level. The anti-mineralocorticoid given intracerebroventricularly, however, caused an elevation of plasma corticosterone up to 60 min after the injection. Exposure of the rats to a novel environment resulted in a large increase in the plasma corticosterone level, which was slightly reduced in the rats treated with the anti-glucocorticoid. In vehicle-treated rats, the level returned to basal values at 90 min, while in the anti-glucocorticoid- and anti-mineralocorticoid-treated groups, it remained elevated for prolonged periods. The present study thus shows that (1) the anti-glucocorticoid RU38486 via the brain GR has no effect on the basal plasma corticosterone level in the morning but interferes with a glucocorticoid negative feedback following stress and (2) the anti-mineralocorticoid RU28318 via the brain MR elevates the basal plasma corticosterone level and enhances adrenocortical secretion following stress. Accordingly, both antagonists caused prolonged adrenocortical secretion following stress. Such an effect caused by the anti-mineralocorticoid is probably due to an enhanced stress responsiveness resulting from a blockade of the limbic MR and that caused by the anti-glucocorticoid resulting from a blockade of GR involved in the termination of the stress response.

ISSN:0028-3835    

DOI:10.1159/000125210

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

To test whether or not splanchnic neural input to the adrenal gland affects secretion of steroids from the adrenal cortex, the thoracic splanchnic nerve was electrically stimulated in pentobarbital-anesthetized dogs after hypophysectomy and replacement with physiological concentrations of ACTH. An adrenal vein cannula was placed to permit measurement of cortisol, corticosterone, 11 -deoxycortisol, epinephrine and norepinephrine secretion rates and adrenal blood flow. Plasma ACTH was measured and the presentation rate of ACTH was calculated as the product of plasma ACTH concentration and adrenal plasma flow. Dogs were infused initially with ACTH for 60 min at 2 ng/min followed by infusion for 60 min at 10 ng/min. Within each infusion period, the distal end of the nerve was stimulated (20 V; 0.5-ms pulse duration) at 4 and at 20 Hz for 10 min each. Nerve stimulation resulted in a frequency-dependent increase in mean arterial pressure, in epinephrine and norepinephrine secretion and in adrenal blood flow. Arterial ACTH remained constant during nerve stimulation; however, increased adrenal blood flow resulted in increased presentation rate of ACTH to the adrenal. Cortisol secretion increased in response to nerve stimulation at 4 and 20 Hz during infusion of 2 and 10 ng/min ACTH and occurred prior to changes in presentation rate of ACTH. Corticosterone secretion also increased after stimulation at both frequencies, but the response was observed only during infusion of 10 ng/min ACTH. In contrast, 11-deoxycortisol decreased after nerve stimulation at 4 Hz but showed no response after stimulation at 20 Hz during infusion of 2 and 10 ng/min ACTH. Steroid ratios were calculated to assess the possible involvement of specific steroidogenic enzymes in the observed responses. The cortisol to 11-deoxycortisol ratio was increased, whereas the cortisol to corticosterone ratio was not affected by nerve stimulation, suggesting a change in 11-β-hydroxylase activity. These data show that splanchnic nerve stimulation can increase cortisol secretion independently of changes in arterial ACTH. The effect of splanchnic nerve activity on cortisol secretion may result from increasing vascular delivery of ACTH to the adrenal, from release of a non pituitary humoral factor with steroidogenic activity or from direct stimulation of steroidogenesis by an adrenal neurotransmitter substance

ISSN:0028-3835    

DOI:10.1159/000125211

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The aim of the present study was to further characterize the site of action of nicotine-induced hypothalamo-hypophyseal-adrenal (HHA) activation. A systemic injection of nicotine in concentrations of 65–2,100 µg/kg elevated serum corticosterone (CS) concentrations in a time and dose-dependent manner. Serum ACTH levels were also significantly increased. Pretreatment with dexamethasone (40 µg/kg) or the nicotinic antagonist, mecamylamine (1 mg/kg), abolished the ACTH and CS secretory responses to nicotine. Intracerebroventricular administration of antinicotinic acetylcholine receptor antibodies, prepared from the serum of myasthenia gravis patients, completely inhibited the nicotine-induced HHA activation. Bilateral lesions of the paraventricular nucleus similarly inhibited the nicotine-induced adrenocortical activity. These results suggest that nicotine activates the HHA axis by a central mechanism which ultimately requires the integrity of the paraventricular nucleus. Moreover, these findings indicate that the nicotinic adrenocortical effect is mediated specifically through activation of central nicotinic cholinergic recept

ISSN:0028-3835    

DOI:10.1159/000125212

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

In mammals including human, it is generally accepted that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism in which somatostatin (SRIF) may be involved. To explore a physiological role of SRIF-mediated GH autoregulation, the effect of exogenous human GH administration on plasma rat GH response to [D-Ala2, Me27]-human GH-releasing hormone-(l-28)-agmatine (hGHRH-analog), which does not crossreact with anti-rat GH-releasing hormone γ-globulin (GHRH-Ab), was examined in conscious male rats treated with GHRH-Ab in the absence and presence of anti-SRIF γ-globulin (SRIF-Ab). Enhanced SRIF release during a trough period of natural pulsatile GH secretion, suggested by the blunted GH response to exogenous hGHRH-analog, no longer occurred when major GH secretory bursts were abolished by GHRH-Ab treatment. On the other hand, when hGH was administered in GHRH-Ab-treated rats so as to simulate the quantity and dynamic change of GH in hypophysial portal circulation in rats exhibiting pulsatile GH secretion, hGHRH-analog-induced GH rises were significantly suppressed during the period corresponding to a GH trough. This suppression was completely prevented by simultaneous treatment with SRIF-Ab. Furthermore, administration of bovine GH, but not ovine prolactin, resulted in significant suppression of hGHRH-analog-provoked GH rises. These findings suggest that enhanced SRIF release during a trough period of spontaneous GH secretory rhythm is induced by the preceding GH secretory burst, and also suggest a possible role for SRIF-mediated GH autoregulation in a physiological stat

ISSN:0028-3835    

DOI:10.1159/000125213

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Cultured rat and ovine anterior pituitary cells were treated with a range of doses (0.01–1,000 nM) of arginine vasopressin (AVP) and ovine corticotropin-releasing factor (CRF), alone or in combination, and medium and cell content of immunoreactive (ir-)ACTH determined. In rat cells, a dose-response curve to CRF was obtained, with a threshold dose of 0.1 nM; AVP was much less effective alone, but augmented CRF responses when administered with CRF. In ovine pituitary cells AVP markedly stimulated ACTH release in a dose-dependent fashion, and with a threshold of 0.1 nM 100 nM. In combination, subthreshold doses of AVP potentiated rat pituitary cell responses to CRF; addition of 1 nM of AVP to varying doses of CRF was more effective in terms of ACTH release than addition of 1 nM of CRF to increasing doses of AVP. In contrast, in ovine cells the addition of 1 nM CRF to increasing doses of AVP elicited a larger ACTH response than the addition of 1 nM AVP to increasing doses of CRF. Dexamethasone pretreatment (5 nM) for 48 h significantly decreased CRF potentiation of AVP-stimulated ACTH release in ovine cells. These studies confirm that CRF is a more potent stimulus of ACTH release than AVP in the rat, and establish that in contrast AVP is a much more potent stimulus of ACTH secretion than CRF in isolated ovine pituitary cell

ISSN:0028-3835    

DOI:10.1159/000125214

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

LH and FSH basal secretion rates (BSR) in vitro of pituitary fragments from female rats at metestrus or following ovariectomy parallel changes seen in serum gonadotropins. These findings led us to suspect that in vitro BSR of fragments depended on prior exposure to GnRH or lingering GnRH in the culture. We compared pituitaries removed from rats in two cycle stages, proestrus (PRO) and metestrus (MET). Rats were given a single injection of a potent GnRH antagonist, Antag – WY 45760 -[Ac-β(2)-D-Nal1, 4-F-D-Phe2, D-Trp3, D-Arg6]-LHRH, or oil prior to sacrifice at 09.00 h on PRO or MET. Pituitary fragments were perifused for 8 h. To test the effects of Antag in vitro some pituitaries from oil-injected rats were perifused with medium containing 1 µM Antag for the first 4 h. Starting at 5 hall chambers received hourly 10-min pulses of 1 µM GnRH. In PRO rats Antag injection in vivo lowered LH BSR to 50% and FSH to 70% of oil-treated controls. Surprisingly, Antag administered in vitro suppressed LH BSR to 30% and FSH to 55% of controls. In pituitaries from MET rats, BSR of LH and FSH were 20 and 70% of control PRO values and were unaffected by Antag treatment in vivo or in vitro. In PRO pituitaries LH and FSH responses to the first GnRH pulse were blunted by Antag in vivo but responses to subsequent pulses were unaffected; MET responses were not different from controls. In vitro Antag suppressed GnRH-stimulated release to 10–20% of controls at both cycle stages. The lower effectiveness of Antag in suppressing FSH has not been shown previously in vitro, but is consistent with in vivo studies in this laboratory. The relative ineffectiveness of the Antag in lowering BSR in MET compared to PRO pituitary fragments suggests that there is less GnRH present, consonant with data showing lower in vivo GnRH release and pituitary receptor levels in MET rats. Our findings suggest that pituitary fragments retain an appreciable amount of endogenous GnRH that stimulates apparent ‘basal’ gonadotropin secretion and that the concept of basal in vitro secretion rate in fragments needs ree

ISSN:0028-3835    

DOI:10.1159/000125215

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The role of diencephalic cholinergic neurotransmission in regulating hypothalamic-pituitary-adrenocortical (HPA) axis was investigated by means of administration of hemicholinium-3 (HC-3), a blocker of acetylcholine synthesis, in the third ventricle of hemispherectomized pigeons. Except for an early increase in ACTH and corticosterone levels following injection as a bolus of HC-3 that was ascribed to some stress-like situation, all data indicated that hypothalamic acetylcholine depletion resulted in inhibiting effects on the HPA axis. Twenty-four hours after injection of 6 µg of HC-3, the response to acute stress was markedly reduced in both magnitude and duration. Permanent instillation of HC-3 in the third ventricle at the rate of 0.25 µg/h for 9 days led to lowered basal resting HPA activity and severely affected the development of adaptation to chronic intermittent stress. The anticipatory conditioned, endocrine response did not appear whereas attenuation of the poststress component was amplified. It is suggested that cholinergic mechanisms are involved in modulating the HPA function and particularly the conditioning process that takes place in the course of adaptation of the HPA response to chronic intermittent application of the same stresso

ISSN:0028-3835    

DOI:10.1159/000125216

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Growth hormone (GH) release and cAMP content were measured in monolayer cultures of anterior pituitary cells after β-adrenergic and GH-releasing factor (GRF) receptor activation. Isoproterenol (Iso, ED50 – 20 nM) was less potent than GRF (ED50 – 20 pM) in stimulating GH release. Iso caused a rapid stimulation of GH release that was maximal after 15 min and declined thereafter, while GRF caused a more gradual increase in GH secretion that was maximal after 30 min and remained elevated after 3 h. Both Iso- and GRF-stimulated GH release were preceded by an increase in cAMP content in the pituitary cells. Further, the addition of 3-isobutyl-1-methylxanthine (IBMX) to the medium enhanced the GH-stimulatory and cAMP-accumulating effects of both secretagogues. Experiments performed with native catecholamines and synthetic catecholamine agonists and antagonists indicated that the GH-stimulatory effect of Iso was mediated by a mixed population of β1-adrenergic and β2-adrenergic receptors. Additionally, experiments performed with cultured Gα tumor cells, found that incubation with GRF, Iso, vasoactive intestinal polypeptide, forskolin, or cholera toxin caused an increase in cAMP content in the cells. However, compared to the responses observed in primary pituitary cultures the GH secretory response to these agents was comparatively small. Together, these studies suggest that a mixed population of β1-adrenergic and β2-adrenergic receptors may act, at least in part, on somatotrophs in the anterior pituitary to stimulate GH release. Although both GRF and β2-adrenergic receptor agents affect GH release through a common second messenger system, their differing pharmacokinetic properties suggest distinct intracellular

ISSN:0028-3835    

DOI:10.1159/000125217

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Both thyrotropin-releasing hormone (TRH) levels in the hypothalamus and thermoregulatory responses were assessed in rats after they had been equilibrated to each of three ambient temperatures (Ta: 8, 22 and 30 °C) tested. Cold exposure, in addition to elevating TRH levels in the hypothalamus, led to increased metabolism and cutaneous vasoconstriction in rats at Ta = 8 °C. In contrast, heat exposure resulted in decreased metabolism and cutaneous vasodilatation in rats accompanied by no change in hypothalamic TRH levels at Ta = 30 °C. In addition, rats were chronically implanted with a cerebroventricular cannula to allow administration of the pyrogenic substance polyriboinosinic acid-polyribocytidylic acis (Poly I:C) into the brain at Ta = 22 °C. Intracerebroventricular administration of Poly I:C, in addition to elevating hypothalamic TRH levels, produced a fever with a latency of onset of about 30 min. The fever induced by Poly I:C was brought about by increased metabolism and cutaneous vasoconstriction in rats. The results suggest that either cold stress or Poly I:C injection elevates TRH levels in rat hypothalamus and thus induces thermogenic reacti

ISSN:0028-3835    

DOI:10.1159/000125218

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Immunoreactive prolactin (ir-PRL) has been identified in the cerebrospinal fluid (CSF) and brain of the male and female rat. In this study we determined the concentration of ir-PRL in the CSF and hypothalamus under conditions known to increase or decrease serum PRL. Hypophysectomy (60 days) significantly decreased the concentration of ir-PRL in the CSF of male (4.9 ± 0.7 vs. 3.0 ± 0.3 ng/ml) and female (5.8 ± 0.9 vs. 3.1 ± 0.5 ng/ml) rats. However, the effect of long-term hypophysectomy on hypothalamic ir-PRL was gender-dependent. That is, in the male rat hypophysectomy did not affect the content of ir-PRL in the median eminence, ventral hypothalamus or dorsal hypothalamus. In contrast, in the female rat, long-term hypophysectomy decreased the content of ir-PRL in the median eminence, ventral hypothalamus, and dorsal hypothalamus 37, 40, and 47%, respectively. Estradiol replacement to the hypophysectomized female rat normalized the content of ir-PRL in the median eminence (96 ± 5.8 to 131 ± 9.6 ng/mg protein), ventral hypothalamus (11 ± 0.6 to 16.0 ± 1.1 ng/mg protein), dorsal hypothalamus (4.7 ± 0.4 to 8.6 ± 0.4 ng/mg protein), and the concentration ir-PRL in the CSF (2.5 ± 0.3 to 4.6 ± 0.4 ng/ml). In intact female rats, administration ofhaloperidol induced a marked hyperprolactinemia, and significantly increased CSF ir-PRL (5.1 ± 1.5 vs. 18.0 ± 3.8 ng/ml). However, in the same rats, the content of ir-PRL in the median eminence was significantly decreased while the ir-PRL content in the ventral hypothalamus and dorsal hypothalamus was unaffected. Administration of haloperidol to hypophysectomized female rats did not affect the concentration of ir-PRL in the CSF, but decreased the content of ir-PRL in the median eminence (83.0 ± 7.3 to 62.6 ± 6.8 ng/mg protein). The detection of ir-PRL in the CSF of hypophysectomized male and female rats indicates that CSF ir-PRL is not completely dependent on plasma ir-PRL. The increase in CSF and hypothalamic ir-PRL in estradiol-, but not haloperidol-, treated hypophysectomized female rats indicates that hypothalamic and CSF ir-PRL is regulated by an estrogen-dependent mechanism at an extrapituitary site. In addition, the failure of hypothalamic ir-PRL to parallel changes in either plasma or CSF ir-PRL indicates that hypothalamic ir-PRL is not derived from the plasma or CSF. In contrast, this study suggests that hypothalamic ir-PRL may be one so

ISSN:0028-3835    

DOI:10.1159/000125219

出版商:S. Karger AG    

年代:1989

数据来源: Karger