摘要:

The effects of chronic cortisol treatment on neuroendocrine and behavioral responses to serotonim (5-HT1) receptor agonists were studied in conscious, freely moving rats. Seven-day cortisol treatment (25 mg/kg/day with osmotic minipumps) markedly suppressed basal plasma corticotropin (ACTH) and corticosterone concentrations, indicating a suppression of the hypothalamo-pituitary-adrenocortical axis. Cortisol also decreased body weight, food intake, plasma norepinephrine (NE), and epinephrine (E) levels. In the drug challenge studies, we used two 5-HTι agonists, the 5-HT1B and 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), to examine the effect of cortisol on their behavioral and neuroendocrine effects. After 7-day cortisol treatment, plasma prolactin responses to both m-CPP and 8-OHDPAT were significantly decreased. While the plasma NE, E, and food intake responses to m-CPP were also significantly reduced by cortisol treatment, these same responses to 8-OHDPATwere unchanged. The effect of m-CPP on locomotor activity was also decreased. Since only the responses to m-CPP and 8-OHDPAT previously shown to be antagonized by pretreatment with the 5-HT1/5-HT2 antagonist, metergoline, were significantly attenuated after cortisol treatment, these changes may be specific to 5-FΓT receptors. These data indicate that chronic exposure to high glucocorticoid levels alters 5-HT1 receptor-mediated functions and provides additional evidence relevant to the contribution of glucocorticoid elevation to the symptoms of depressio

ISSN:0028-3835    

DOI:10.1159/000125248

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Terminating the pregnancies of female rats on day 16 (D 16) by hysterectomy and ovariectomy (HO) and administering estradiol benzoate (EB) systemically or centrally into the medial preoptic area (MPOA) stimulates the onset of maternal behavior 48 h later. Since estrogen’s effects are mediated through its intracellular receptors, the present studies measured nuclear and cytosol estrogen receptor concentrations in the POA and hypothalamus (HYP) of female rats during the 48 h when estrogen is active in stimulating maternal behavior. A low dose of EB (5 µg/kg) was used which was effective in stimulating maternal behavior in D16HO females but not in nonpregnant HO females of two types. In D16 animals there was a significantly higher concentration of nuclear receptors in the POA than in the HYP at time 0 (before HO and EB) but thereafter levels were similar in the two areas: nuclear receptor levels rose between 6 and 24 h after which they declined. In nonpregnant females, nuclear receptor levels at time 0 were low in both brain regions, rose significantly between 0 and 24 h, and significantly declined between 24 and 48 h similar to the D16 females. There were minimal differences in cytosol receptor levels among all groups at any time. Results from additional groups, nonpregnant HO females given 100 µg/kg EB and D16H animals (females whose pregnancies were terminated by hysterectomy only and their ovaries left intact), both of which exhibit maternal behavior at 48 h, support the idea that a high level of nuclear estrogen receptors in the POA followed by a sustained high level is necessary for estrogen stimulation of maternal behav

ISSN:0028-3835    

DOI:10.1159/000125230

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Bolus doses of GH-releasing hormone (GHRH), 1 µg/kg i.v., were given to two groups of adult patients with growth hormone deficiency (GHD): 9 with Hand-Schüller-Christian disease (HSCD, presumed hypothalamic GHD) and 9 with idiopathic GHD (IGHD, etiology unknown). Six patients in each group were then given further GHRH doses daily for 5 days, and the GH responses to GHRH were measured over 3 h on day 1 and day 5. Plasma levels of insulin-like growth factor-1 (IGF-1) were measured twice daily on days 1 and 5 during GHRH treatment. All patients with HSCD had measurable GH responses to the first dose of GHRH, with a mean peak response of 6.4 ± 2.1 ng/ml (X ± SE). Only 5 of 9 patients with IGHD had GH responses above the detection limits of the assay; their mean peak response, 1.3 ± 0.2 ng/ml, was significantly lower than the GH responses of the HSCD patients (p < 0.05). Responses in both groups of patients were lower than those previously observed in normal adult men (35 ± 8 ng/ml; p < 0.01). Five days of daily stimulation with GHRH significantly (p < 0.01) increased the GH response in both groups of patients. The rise was greater in patients with HSCD than with IGHD (HSCD, 5.1 ± 2.5 ng/ml on day 1, vs. 12.0 ± 6.8 ng/ml on day 5; IGHD, 1.4 ± 0.3 ng/ml vs. 2.9 ± 0.6 ng/ml). Plasma IGF-I levels rose significantly over the 5 days in both groups; this rise was also greater in the HSCD patients (HSCD, 0.37 ± 0.06 vs. 0.64 ± 0.1 U/ml; IGHD, 0.38 ± 0.12 vs. 0.45 ± 0.12 U/ml, p < 0.05). Responses in this group of HSCD patients confirm the expectation that patients with ‘pure’ hypothalamic GHD should have GH responses to GHRH, and that diminished initial responses reflect somatotroph atrophy which can be reversed with repeated

ISSN:0028-3835    

DOI:10.1159/000125231

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Neonatal rats exhibit a period of diminished pituitary and adrenocortical responses to stress during the first 2 weeks of life. Since thyroid hormones are known to affect brain development, modulation of these responses to stress by alterations in thyroid hormone status have been investigated in hypothyroid (Hypo) and hyperthyroid (Hyper) rat pups. Changes in ACTH and corticosterone (B) levels were measured under basal and stress conditions (3 min exposure to ether vapors) in neonates of various ages (day 5–21). Basal T4 and corticosterone-binding globulin (CBG) levels were also measured. Hypo pups were obtained from methimazole-treated mothers and hyperthyroidism was induced by daily subcutaneous injections of L-T4 (100 µg/kg BW) from birth on. In Hyper rats, premature onset of ACTH and B responses to stress was observed in 5-day-old rats while significant ACTH and B secretion only appeared by day 10 in vehicle-injected rats. By contrast, ACTH and B responses to stress were delayed in Hypo pups and only occurred by day 21. The lack of ACTH and B responses to stress of 14-day-old Hypo rats could be reversed by one single L-T4 injection (100 µg/kg BW) given 24 h, but not 4 h prior to exposure to stress. On day 21, smaller (p < 0.05) stress-induced ACTH release was observed both in Hypo and Hyper rats compared to intact rats, concomitant with a diminished ACTH secretion following exogenous ovine CRF(10 µg/kg BW, i.p.) administration. T4 treatment increased pituitary ACTH stores and produced marked increases in plasma B (4.5-fold on day 5, 2.5-fold on day 21), and CBG concentrations (2-fold on day 5, 2.6-fold on day 21) at all ages. In contrast, Hypo rats exhibited no changes in pituitary ACTH stores, but reduced plasma CBG concentrations throughout the neonatal period. Basal plasma B levels were increased in Hypo rats on day 5 and 10 comparable on day 14 or diminshed on day 21 as compared to intact rats, suggesting that the normal developmental pattern of B is delayed in hypothyroidism. In conclusion, we have shown that (1) thyroid hormones modulate the onset of ACTH and B responses to stress, most likely via changes in B and CBG concentrations, (2) the lack of ACTH and B response to stress in hypothyroid rats can be restored by one single injection of L-T4 and (3) a diminished ACTH and B response to stress observed at weaning in Hypo and Hyper rats is associated with a decrease in pituitary sensitivity to exogenous

ISSN:0028-3835    

DOI:10.1159/000125232

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Pineal β-adrenoceptor density and affinity in ewes are modified in a season-dependent manner by gonadal steroids and by the sympathetic innervation of the gland. The present study was undertaken to relate the steroidal effects on the receptors to post receptor endocrine events, and to investigate the influence of the sympathetic innervation of the pineal gland on these events. Plasma melatonin and prolactin profiles were determined during anestrus and during the normal breeding season in ewes subjected to sympathetic denervation of the pineal and/or a range of steroid-related treatments. Wherever valid comparisons could be drawn between effects of the treatments on β-adrenoceptor variables and on circulating hormone levels, similar effects were noted. Further, ganglionectomy influenced hormone profiles similarly to estradiol under all conditions tested. It appears that gonadal steroids (estradiol) and the sympathetic neurotransmitter noradrenaline have opposing actions on prolactin levels, just as they have on pineal β-adrenoceptor binding affinity. These findings suggest that steroid-mediated changes in receptor number and affinity are reflected in post receptor endocrine events. In addition, other factors (e.g. photoperiodic information transmitted via the sympathetic innervation) also play important roles in the regulation of the observed hormonal profiles. A steroid-mediated feedback regulation of pituitary prolactin release, partly direct and partly via pineal melatonin release, is suggest

ISSN:0028-3835    

DOI:10.1159/000125233

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Proopiomelanocortin (POMC) gene expression in the anterior pituitary (AP) gland has previously been shown to be positively regulated by CRF and AVP and negatively regulated by glucocorticoids. In the neurointermediate lobe () of the pituitary, however, POMC gene expression is under tonic inhibitory dopaminergic control. In the present study we have used hypothalamopituitary intact (HPI), ovariectomized (OVX), and OVX/hypothalamopituitary disconnected (OVX/HPD) ewes to examine direct (i.e. nonhypothalamic) effects of glucocorticoids on POMC gene expression in both the AP and the . There was no difference between POMC mRNA levels in intact and OVX sheep. In intact animals treated with dexamethasone, AP POMC mRNA levels were half those of controls. POMC mRNA levels were increased 3-fold in OVX/HPD sheep, compared with OVX, and lowered by dexamethasone to half OVX/HPD levels. In the , hypothalamopituitary disconnection resulted in slightly higher mean POMC mRNA levels than in intact animals but the large intragroup variation did not allow a significant change. Dexamethasone administration had no effect on levels of POMC mRNA in intact or OVX/HPD sheep.

ISSN:0028-3835    

DOI:10.1159/000125234

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Previous studies have demonstrated α2-inhibitory regulation of central nervous system (CNS) noradrenergic and arginine vasopressinergic systems. We tested the hypothesis that α2-inhibition of CNS noradrenergic and vasopressinergic systems is tonic in nature by measuring the response of cerebrospinal fluid (CSF) norepinephrine (NE) and arginine vasopressin (AVP) to the α2antagonist yohimbine in 7 young normal male human subjects. We also evaluated the tonic nature of α2-inhibition of the sympathetic nervous system (SNS) and of AVP release into plasma by measuring the response of plasma NE and plasma AVP to yohimbine. CSF NE was significantly higher following yohimbine as compared to placebo. In contrast CSF AVP did not differ between yohimbine and placebo conditions. Similarly, plasma NE was significantly higher following yohimbine as compared to placebo, while plasma AVP was unchanged. These results support a tonic α2-inhibitory regulatory mechanism for both CNS noradrenergic systems and sympathetic outflow. Such tonic α2-inhibition could not be demonstrated for regulation of AVP levels in CSF or plasma in h

ISSN:0028-3835    

DOI:10.1159/000125235

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Accurel polypropylene mini-devices, loaded with arginine vasopressin (AVP) and implanted in the lateral cerebral ventricle were used to centrally treat heterozygous (HE) and homozygous (HO) Brattleboro (BB) rats. After 1 week of treatment, the concentration of AVP receptors in the HO-BB rat septum decreased from 19.4 ± 2.6 to 12.4 ± 1.1 fmol/mg protein, but remained unchanged in the HE-BB rat (10.7 ± 0.8 and 7.0 ± 1.1 fmol/mg protein). In the HO-BB rat the [Η]-AVP equilibrium dissociation constant (KD) of the septal AVP receptor decreased following AVP treatment (from 4.17 ± 0.7 to 1.97 ± 0.3 nM) compared to that of control animals. This decrease in receptor number following AVP treatment was accompanied by a decrease in the postreceptor response to AVP as measured by the AVP-stimulation of [3H]-inositol-1-phosphate (IP1) accumulation (22.0 ± 6.1%) when compared to untreated animals (54.3 ± 8.3%). This apparent AVP-induced down-regulation was not due to occupancy of the binding sites by AVP since preincubation of the tissue at 37 °C for 60 min (which was able to cause near-complete dissociation of the hormone-receptor complex) did not result in an increased number of binding sites upon reexposure to [3H]-AVP. This study thus provides evidence for the homologous down-regulation and desensitization in terms of [3H]-IP1 accumulation (phosphoinositide hydrolysis) of AVP receptors in the septum of t

ISSN:0028-3835    

DOI:10.1159/000125236

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Sex differences in the hypothalamic control of growth hormone (GH) secretion were investigated by measuring rat GH-releasing factor (rGRF) and somatostatin in male and female rats. Rat GRF-like immunoreactivity (rGRF-IR) was higher in the median eminence and hypothalamic tissue outside of the median eminence of adult (90-day-old) male compared to female rats. A similiar pattern of rGRF-IR content was found in the median eminence of 35-day-old rats. This sex difference developed between days 25 and 35 of age, during which time serum concentrations of insulin-like growth factor (IGF-1) and body weight increased in both sexes. To a lesser extent, the content of somatostatin-like immunoreactivity (SLI) was higher in the median eminence of adult female rats compared to male rats. Whole hypothalamic rGRF-IR and SLI contents were influenced only moderately by adult gonadectomy or gonadal steroid treatments. For example, estrogen increased rGRF-IR content in castrated rats, but orchidectomy alone or orchidectomy followed by testosterone did not influence rGRF-IR content. Additionally, whole hypothalamic SLI content was unaffected by orchidectomy or orchidectomy followed by testosterone or estrogen. One month after ovariectomy, rGRF-IR and SLI in whole hypothalamic fragments were similar to their respective contents in gonad-intact males. However, ovariectomy followed by estrogen or testosterone did not restore rGRF-IR content and partially restored SLI content to levels seen in gonad-intact females.

ISSN:0028-3835    

DOI:10.1159/000125237

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

These studies examined the mechanisms responsible for the paucity of basal LH pulses during estrus. We confirmed our earlier observations that constant infusion of naloxone during estrus results in the immediate appearance of pulsatile LH secretion during estrus, consisting of LH peak heights and LH interpulse intervals that are similar to those observed during other days of the estrous cycle. We then tested whether the proestrous surge of progesterone was responsible for the suppression of pulsatile LH secretion during estrus. Three treatment regimens were used on proestrus to either block progesterone secretion (pentobarbital) or block its action (progesterone antiserum or the progesterone antagonist, RU 486). After treatment at 12.00 h on proestrus, blood samples were collected during estrus every 10 min for 4 h, and the plasma samples were analyzed for the pattern of LH secretion. Treatment with pentobarbital (35 mg/kg at 12:00 h) blocked the proestrous surges of LH and progesterone and resulted in pulsatile LH secretion during estrus. The LH interpulse interval (72 ± 7 min) was somewhat slower than that observed in the naloxone-infused animals (54 ± 8 min). Simultaneous treatment with pentobarbital and progesterone at 12:00 h on proestrus completely prevented the appearance of LH pulses during estrus. Treatment with either progesterone antiserum (0.5 ml, i.v.) or RU 486 (1 mg s.c.) resulted in the initiation of pulsatile LH secretion during estrus. In the RU 486-treated animals, LH peak heights and LH interpulse intervals were similar to those observed in naloxone-infused animals and during other days of the estrous cycle. These studies demonstrate that the suppression of pulsatile LH secretion during estrus is dependent on endogenous opioid tone. In addition, the proestrous surge of progesterone may be responsible for this suppression during estrus, since blocking progesterone secretion or blocking its action restores pulsatile LH secretion on estrus. We hypothesize that the proestrous surge of progesterone may cause an increase in endogenous opioid tone which then suppresses GnRH release and pulsatile LH secretion during estru

ISSN:0028-3835    

DOI:10.1159/000125238

出版商:S. Karger AG    

年代:1989

数据来源: Karger