摘要:

Synthetic ovine corticotropin releasing factor (oCRF) and human CRF were given as an intravenous bolus to 6 healthy volunteers in 4 different dosages (oCRF: 25, 50, 100 and 200 µg) respectively, 2 different dosages (hCRF: 50 and 100 µg). ACTH and cortisol were measured over a 2-hour period after CRF injection. CRF immunoreactivity was measured with a newly developed homologous radioimmunoassay for both oCRF and hCRF. All CRF dosages tested led to a definite ACTH response compared to placebo control. No dose dependency of side effects was observed. Furthermore, there was no clear-cut dose response relationship between the injected CRF dosages and the maximal ACTH- and cortisol levels. However, when the area under the ACTH and cortisol-response curves after oCRF were compared a dose-response relationship emerged, which could not be demonstrated in the same way for the two hCRF dosages. Serum CRF immunoreactivity correlated to the injected dosage. The halftime of serum disappearance for oCRF was 18 min, and hCRF, 9 min. The maximal ACTH responses after injection of oCRF and hCRF were not significantly differen

ISSN:0028-3835    

DOI:10.1159/000124240

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The purpose of these studies was to determine the temporal requirements and time of day required for progesterone (P4) to amplify versus extinguish LH surges. The experimental animal model used in these studies was the 7-day ovariectomized rat (day 0) treated continuously with estradiol (E2) for 2–4 days (days 2, 3 or 4). In these studies we also examined the changes which occur in estrogen nuclear (ERn) and progestin cytosol (PRc) receptor concentrations in the preoptic area (POA), medial basal hypothalamus (MBH), corticomedial amygdala (CMA) and pituitary gland (PIT) associated with these physiological responses. When two P4 capsules (50 mg/ml) were placed subcutaneously at 09.00 h on day 2 and removed 3 h later (12.00 h), LH surges were amplified that afternoon. 24 and 48 h later (days 3, 4) phasic LH release reoccurred albeit in reduced concentrations compared to the LH values obtained in E2-treated rats on day 2. In contrast, if P4 capsules remained in situ for < 24 h, LH surges did not reappear on day 3. In a separate group of E2-treated rats, P4 capsules were placed subcutaneously at 15.00 h and removed at 21.00 h on day 2. Only minor increases in LH occurred on day 3 compared to E2-treated controls. Thus, both the duration of time and hour of day that the hypothalamo-pituitary unit is exposed to P4 seem important in determining which component of the biphasic LH response (amplification vs. inhibition) will occur. When ERn and PRc concentrations were measured, neither 3 nor 24 h of P4 exposure affected ERn levels in the POA, MBH, CMA or PIT. However, 3 h of P4 exposure significantly reduced PRc concentrations in POA, MBH and PIT at 15.00 h on day 2, but by day 3, PRc values returned to the control levels observed in rats receiving only E2 on days 2 and 3. Continuous P4 exposure not only significantly decreased PRc levels in POA, MBH and PIT by 15.00 h on day 2, but these receptor levels still were depressed in MBH and PIT at 15.00 h on day 3. Since PRc concentrations recovered in rats exposed to only 3 h of P4 on day 2 we next examined whether P4, given at 09.00 h on days 3 or 4, would affect afternoon LH surges on these days. Both amplification and advancement of the time of LH surges occurred in these rats. Thus, with the restoration of control PRc levels in day-3 rats briefly exposed to P4 on day 2, physiological competence to respond positively to P4 is also reestablished. The final series of studies examined the effects of P4 on the PRL surges which occur concomitant with phasic LH release. Regardless of the effect of P4 on LH release, this steroid had no effect on phasic PRL release on days 2–4. We recognize that a critical time period exists during which estrogen is required to program those neural processes involved in phasic LH release the following day. Presentation of a P4 stimulus during this interval seems to disrupt some critical estrogen-dependent biochemical events in hypothalamic neurons such that phasic LH release is extinguished the next

ISSN:0028-3835    

DOI:10.1159/000124241

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In order to determine the role of the pineal gland in mediating the effects of long-term light deprivation on prolactin (PRL) cell activity in a highly photosensitive species, PRL synthesis, storage and release were determined in both female and male Syrian hamsters that were either blind, blind and pinealectomized or left intact for 14 weeks. PRL release was determined in vivo by measuring the amount of immunoreactive (RIA) PRL in the serum of the animals in each group with a heterologous RIA for hamster PRL. Blinding resulted in a 98 and 88% reduction in serum PRL levels in female and male hamsters, respectively. Pinealectomy largely prevented the suppressive effects of blinding on PRL release; however, PRL levels in blind pinealectomized animals were intermediate between those in intact and blind animals. PRL synthesis was evaluated by assessing the amount of 3H-leucine incorporated into PRL by anterior pituitaries in vitro. In female hamsters 14 weeks of light deprivation resulted in an 87% decrease in the incorporation of 3H-leucine into newly synthesized PRL whereas in males only a 40% reduction occurred. While pinealectomy completely prevented the inhibitory effects of blinding on PRL synthesis in males, it was less effective in female hamsters inasmuch as PRL synthesis was still nearly 50% lower in blind pinealectomized animals than in controls. Stored PRL, as represented by the total amount of RIA-PRL in vitro, was 96% lower in blind female hamsters as compared with intact controls; in blind male hamsters, stored PRL was reduced by 77%. As in the case of PRL synthesis, pinealectomy completely prevented the suppressive effects of blinding on PRL storage in males; however, it was only partially effective in female animals since total RIA-PRL was still 58% less than in controls. In conclusion, it appears that the inhibitory effects of light deprivation on PRL cell activity are more severe in female than in male hamsters. Furthermore, while the suppressive effects of blinding on PRL cell function in males seem to be pineal-dependent, they appear to be at least partially pineal-independent in female animals.

ISSN:0028-3835    

DOI:10.1159/000124242

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In female rats ovariectomy (OVX) on the morning of diestrus day 2 resulted in a prompt (within 8 h) and gradual increase in LH release, whereas a similar operation on estrus did not raise serum LH until 24 h later. In proestrous females, OVX in the morning neither prevented the anticipated LH surge on that evening, nor increased LH release on the next morning. Since circulating concentrations of estradiol (E2) are progressively increased during diestrus day 2 and proestrus, this pattern of E2 secretion may affect the acute increase in LH secretion following OVX. To test such a hypothesis, we examined the effects of large, sustained or large, transient increases in circulating estrogen on the subsequent increase in gonadotropin secretion after OVX. On the morning of diestrus day 1 a subcutaneous injection of 20 µg estradiol benzoate (EB) produced prompt and large increases in both serum E2 and estrone (E1) for about 2 days, despite OVX of females at 24 h after the EB injection. An injection of 20 µg 17β-estradiol (E2) also promptly increased both serum E2 and E1. However, the magnitude of the increases in E2 and E1 after 20 µg E2 injection were twice that observed after 20 µg EB, and both E2 and E1 returned to low baseline values within 24 h after the E2 injection. In contrast, administration of 1 µg EB only produced small and transient rises in serum E2 and E1. Under these experimental conditions, it was the injection of 20 µg EB, not 1 µg EB or 20 µg E2, which elicited an LH surge on the next day, and subsequently suppressed the post-OVX increases in both LH and FSH release for 9–10 consecutive days. At 7 days after the injection of 20 µg EB both serum E2 and E1 had returned to low levels for at least 4 days in OVX (6 days) females, but the plasma concentrations of both LH and FSH were significantly less in the EB-treated than oil-injected females, indicating a sustained inhibition of gonadotropin secretion by estrogen. However, two intravenous injections of gonadotropin-releasing hormone (GnRH) elicited similar increases in both LH and FSH release between these two groups of OVX females. These observations are compatible with the hypothesis that a sustained and large rise in circulating E2 and/or E1 may exert a profound inhibition on hypothalamic GnRH release, thereby decreasing pituitary secretion of go

ISSN:0028-3835    

DOI:10.1159/000124243

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The postmortal decay of acetylcholine (Ach) was studied in the cervical spinal cords of rats in conditions of hyper- and hypothyroidism. The modifications of thyroid function were achieved either by chronic (20–25 days) administration of /-thyroxine or of methimazole. The basal metabolic rate and plasma T4 concentration were measured to estimate the degree of modification of thyroid activity. The levels of Ach at the start of postmortal decay were evaluated by extrapolation to time 0 of the curves of the postmortal decay of Ach and the levels of Ach at stabilization were estimated from the means of all the measures made at lapses of time over 100–200 s from death. In low and high hypothyroidism a reduction (53 and 72%, respectively) of the levels of Ach was found. A similar effect was found in hyperthyroidism: a 73 and 63% reduction of Ach levels in high and low hyperthyroidism, respectively. The level of Ach at stabilization of the postmortal decay increased only in hyperthyroid rats. The process by which Ach is destroyed is not modified in hyper- or hypothyroid

ISSN:0028-3835    

DOI:10.1159/000124244

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

We have shown that the implantation of cholecystokinin octapeptide sulfated form (CCK-8-S) or dopamine (DA) in the medial preoptic area (MPO) in ovariectomized estrogen-primed rats induced an enhancement of the afternoon rise in LH secretion. The present study was done to examine the possible functional interaction of both substances in the brain. Two groups of ovariectomized estradiol (5 µg, s.c.)-primed rats were administered intraperitoneally either pimozide (1 mg/kg BW; pimozide-treated group) or 0.1 M tartaric acid as the control solution (pimozide-untreated group). CCK-8-S or DA was implanted in the MPO through chronically implanted guide cannulae and the effects on serum LH and FSH concentrations were compared between both groups. An empty cannula was used as the control. Implantation of either CCK-8-S or DA in the pimozide-untreated group induced marked enhancements of afternoon rises in LH and FSH levels, which normally occurred, but with a lesser magnitude in the animals with the empty cannula. In the pimozide-treated group, however, neither CCK-8-S nor DA induced changes in the LH and FSH levels. It was evident that both effects of CCK-8-S and DA on LH and FSH secretion were blocked by pretreatment with the DA receptor blocker. These data indicate that DA receptors are required to be intact when CCK-8-S implants manifest their action in stimulating gonadotropin secretion

ISSN:0028-3835    

DOI:10.1159/000124245

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Day-night differences in the concentrations of melatonin and serotonin (5HT) were measured in several regions of the chicken brain, pineal gland and serum. Melatonin concentrations are higher at midnight than at midday in 8 of the 10 tissues studied although the amplitudes of these rhythms varied greatly. Day-night differences in the pineal, hypothalamus, thalamus, retina and pons-midbrain regions had the highest amplitudes. 5HT concentrations were rhythmic in only 3 of the tissues studied: the hypothalamus, thalamus and retina. These were also the areas of highest 5HT concentration. Exogenous melatonin, injected at midday, was taken up with similar patterns; the pineal, hypothalamus, thalamus and pons-midbrain contained more melatonin 20 min after injection than did other tissues. The rate of decline of melatonin concentration varied little among all tissues studied, suggesting that the differences among tissue concentrations were due to selective uptake mechanisms rather than specialized degradation pathways. The effects of exogenous melatonin on 5HT concentration were restricted to hypothalamus, thalamus, pons-midbrain, retina and pineal. No effect was seen in cerebellum, optic tectum, neostriatum, hippocampus and medulla oblongata. Together, these data strongly suggest that pineal (and exogenous) melatonin is selectively taken up primarily by three brain regions, hypothalamus, thalamus and pons-midbrain, in which it produces increases in 5HT concentrations. Regional selectivity of uptake may be the mechanism by means of which the effects of melatonin on 5HT-mediated function are restricted to specific brain areas.

ISSN:0028-3835    

DOI:10.1159/000124246

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In a recent experiment, it was found that the dopamine-β-hydroxylase inhibitor, U-14,624, decreases the concentration of cytosol progestin receptors in guinea pig hypothalamus and causes an increase in the concentration of nuclear progestin receptors. In this series of experiments, the possibility that similar effects would be seen in the rat estrogen receptor system in mediobasal hypothalamus and pituitary was tested. U-14,624 caused a time-dependent decrease in the concentration of cytosol estrogen receptors and increase in the concentration of nuclear estrogen receptors in both mediobasal hypothalamus and anterior pituitary gland in ovariectomized rats, both in the absence and presence of low levels of estradiol, as well as in ovariectomized-adrenalectomized rats. The nuclear estrogen receptors that accumulate after U-14,624 injection do not require incubation at 25 ¤C to be assayed, suggesting that they are not occupied by an estradiol-like ligand. The nuclear estrogen receptors that accumulate after U-14,624 treatment are high affinity, with an apparent dissociation constant of approximately 0.1 nM U-14,624 does not compete with (3H)estradiol, in vitro, suggesting that it does not directly interact with estrogen receptors. These results suggest that under some conditions, inhibition of dopamine-β-hydroxylase causes a modification in unoccupied estrogen receptors so that they develop a higher affinity for cell nuclear componen

ISSN:0028-3835    

DOI:10.1159/000124247

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

High-affinity progestin binding sites were found in the brain and pituitary of the female South African clawed frog, Xenopus laevis. Cytosol progestin receptors in the hypothalamus-preoptic area and pituitary were increased in number by estradiol treatment in ovariectomized frogs. The telencephalon also contained high-affinity binding sites, but the concentration was not affected by estrogen priming. Autoradiographic analysis of the distribution of the synthetic progestin 3H-R5020 revealed some lightly labeled cells in the anterior preoptic area and ventral infundibulum of ovariectomized animals. After estrogen priming, many heavily labeled cells were observed in the following areas: ventrolateral striatum and amygdala, anterior preoptic area, ventral infundibular nucleus, laminar nucleus of the torus semicircularis, and anterior pituitary. The areas in which dense accumulations of 3H-R5020 labeled cells were found after estrogen treatment are a subset of areas known to contain estrogen binding sites. The induction of progestin receptors by estradiol may be related to the requirement for both estrogen and progestin to elicit female sexual behavior in this species.

ISSN:0028-3835    

DOI:10.1159/000124248

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Pituitary angiotensin II (ANG) binding sites were characterized by autoradiography in individual male Long Evans (LE) rats, heterozygous Brattleboro (HZ) rats, and homozygous Brattleboro (DI) rats which were water satiated or water deprived. An additional group of DI rats was treated with arginine vasopressin for 1 week. The technique utilized 8-µm pituitary sections which were incubated with 125I-[Sar1]-ANG in concentrations ranging from 25 pM to 10 nM. Angiotensin binding in the anterior pituitary of water-satiated LE rats was characterized by a single class of high-affinity, saturable sites with a Bmax of 1.309 ±119 fmol/mg of protein and a Ka of 0.51 ± 0.03 × 109M–1l. Compared to LE rats the density of ANG-binding sites in anterior pituitary was higher in DI rats (+84.2%), with HZ having an intermediate concentration (+41.6). Dehydration increased the ANG-binding site density in all groups. Five days of water deprivation increased the number of ANG-binding sites by 86.5% and by 36.9% in LE and HZ rats, respectively, when compared to their water-satiated controls. After 1 day of water deprivation, the ANG-binding site density increased by 19.4% in DI rats. No changes in ANG-binding sites occurred after hormonal replacement with arginine vasopressin in water-satiated DI rats. The binding affinity constant of the agonist for the ANG-binding sites compared with LE rats was decreased in both HZ and DI rats (-27.5 and -19.4%) and was also decreased after 5 days of dehydration in LE rats (-34%) when compared to the water-satiated state. Our results demonstrate alterations in ANG-binding sites in the anterior pituitary gland of both dehydrated Brattleboro rats and LE rats. These findings suggest a role for anterior pituitary ANG receptors in the regulation of fluid metabolism in th

ISSN:0028-3835    

DOI:10.1159/000124249

出版商:S. Karger AG    

年代:1986

数据来源: Karger