摘要:

The goal of these experiments was to determine the number and distribution of brain cells that contain progestin receptors (PR) and to determine the effect of estrogen and estrogen plus progesterone on PR content of those cells. Ovariectomized adult female guinea pigs were treated with oil (control), or estrogen followed by oil, or estrogen followed by progesterone. As expected, only those animals treated with estrogen plus progesterone became sexually receptive. The cellular content of PR was determined using a monoclonal antibody to the receptor, and standard immunocytochemical techniques. Analysis of the PR-immunoreactive (PR-IR) cells consisted of: (1) mapping the anatomical distribution of PR-IR cells; (2) analyzing the effect of steroid hormones on PR-IR cell number, and (3) determining the effect of steroid hormones on PR immunoreactivity per cell. PR immunoreactivity was located exclusively in the nuclei of cells in the preoptic area and hypothalamus. The most dense collections of PR-IR cells were found in the preoptic area, ventrolateral nucleus of the hypothalamus, and infundibular nucleus. Estrogen caused a dramatic increase in the number of PR-IR cells in these cell groups. Sequential treatment with estrogen plus progesterone further increased PR-IR cell number, in the preoptic area by 65%, in the ventrolateral nucleus by 38%, and in the infundibular nucleus by 49%. A cell-by-cell rating of the PR immunoreactivity was carried out in these three cell groups. We found that the staining intensity across the populations of PR-IR cells was increased by estrogen and further increased by sequential estrogen plus progesterone. Alterations in cellular PR content may contribute importantly to the ability of progesterone target cell groups to perform their specialized roles in steroid-regulated activity.

ISSN:0028-3835    

DOI:10.1159/000125290

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Oxctocin and vasopressin (AVP) were previously reported to have a diurnal rhythm in cerebrospinal fluid (CSF) collected from the cervical cistern of chaired, intact male rhesus monkeys. In the present study, we continuously sampled CSF from temporary indwelling catheters placed in the spinal subarachnoid space of unanesthetized monkeys maintained on tether and swivel systems. CSF was collected from intact and castrate female rhesus monkeys and intact female and castrate, adrenalectomized male cynomolgus monkeys to determine if oxytocin and AVP rhythms are expressed in spinal subarachnoid CSF, if the magnitude of the CSF rhythm displays a rostral-caudal gradient, and if the rhythm is present in adrenalectomized and castrate monkeys, or is specific to the sex or species of macaque. Monkeys, maintained on a 12-hour light/dark cycle with lights on from 06.00 to 18.00 h, had 19-gauge epidural catheters introduced at the L4-L5 intervertebral space and advanced cephalad in the subarachnoid space. The proximal end of the catheter was connected to a peristaltic pump for continuous removal of CSF (0.5 ml/h) and hourly CSF samples were radioimmunoassayed for oxytocin and AVP. For rostral-caudal studies, the distal tip of the catheter was repositioned every few days to collect CSF from 3 levels of the spinal subarachnoid space: C5–6, T5–6, T12–L1 cervical). Oxytocin also displayed a rhythm in the CSF of adrenalectomized and castrate animals that was similar in pattern and magnitude to that in intact animals indicating that secretory products from the adrenal glands do not play a critical role in modulating the CSF oxytocin rhythm. The pronounced CSF oxytocin rhythm in the lumbar spinal subarachnoid space, an area of the cord known to contain high oxytocin concentrations, suggests local spinal cord secretion or regulation of the CSF oxytocin r

ISSN:0028-3835    

DOI:10.1159/000125291

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Both oxytocin (OXY) and arginine vasopressin (AVP) enhance the effects of corticotropin-releasing factor on ACTH release by the pituitary. One of these, AVP, plays a role in the control of fluid balance and responses to hypoxemic stress in the fetal sheep. To determine the possibility that OXY also participates in fetal neuroendocrine events, OXY-containing neuronal structures must first be demonstrated within the fetal endocrine hypothalamus. OXY-immunoreactive elements were examined in fetal sheep hypothalami late in gestation and compared to AVP-containing structures using immunocytochemical procedures. Six fetal sheep ranging from 126 to 144 days gestational age were delivered via cesarian section from timed pregnant Rambouillet-Columbia ewes and killed by an overdose of anesthesia. The fetal head was perfused via bilateral carotid catheters and processed for immunocytochemical localization of OXY or AVP using the avidin-biotin complex procedure. At all fetal ages examined, OXY- and AVP-containing neurons were found within the paraventricular nuclei (PVN), supraoptic nuclei (SON) and accessory magnocellular hypothalamic nuclei. OXY-containing neurons were found principally in the SON and PVN. They were generally less numerous and less intensely stained than the AVP neurons. In the SON, they concentrated along the dorsal borders of the nucleus above the AVP neurons. In PVN, clusters of OXY cells were located along the dorsal and lateral borders of the nucleus surrounding the AVP neurons; in the periventricular division, they were intermingled with the AVP neurons. Small numbers of OXYaxons were located in the external zone of the median eminence; whereas most OXY axons extended into the hypothalamo-neurohypophyseal tract and posterior lobe of the pituitary. A few of the OXY axons in the pituitary stalk were diverted to the pars intermedia. Likewise, some of the OXY fibers from the external zone of the median eminence entered the pars tuberalis but were rarely found in the distal lobe of the pituitary. In contrast, AVP axons richly innervated the external zone of the median eminence, and neural lobe. Like OXY, AVP axons from the median eminence and the pituitary stalk sent projections to the adenohypophysis. AVP fibers in the pars distalis frequently contacted corticotropes and were more numerous than OXY fibers in this region. These data provide anatomical evidence that OXY and AVP may directly regulate the fetal adenohypophysis. Of these two neuropeptides, AVP predominates anatomically.

ISSN:0028-3835    

DOI:10.1159/000125292

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Plasma PRL levels in male rats are highest during the peripubertal period. We previously reported that the posterior pituitary (PP) contains a potent PRL-releasing factor (PRF), a trypsin-insensitive small peptide which is distinct from known PRL secretagogues. The objectives were to determine the ontogeny of PRF activity in the PP as well as age-related alterations in anterior pituitary responsiveness to PRF. We also explored if the PP contains a nondopaminergic PRL-inhibiting factor (PIF). PRF/PIF activities were assessed by the ability of PP extracts to alter PRL release from cultured anterior pituitary cells. The PP were extracted with perchloric acid and lyophilized, thus eliminating endogenous dopamine. PRF activity in PP extracts from 10- and 20 day-old (d) rats was very low, increased gradually in 30d and 40d rats, and remained unchanged in adult (90d) rats. In a second experiment, age-related changes in anterior pituitary responsiveness to PP extracts from adult rats and to TRH were determined. The responsiveness of anterior pituitary cells from 10d rats to PRF was low, increased dramatically in cells from 20d rats, and was reduced in cells from 30d and adult rats. The responsiveness to TRH was highest in cells from 10d rats. In a third experiment, anterior pituitary responsiveness to age-matched PP extracts was assessed. Only PIF activity was observed when PP extracts from 10d rats were incubated with anterior pituitary cells from 10d rats. In contrast, PP extracts from 20d, 30d and adult rats exhibited only PRF activity when incubated with age-matched cells. Treatment of PP extracts from 10d rats with trypsin abolished their PIF activity, but did not alter the PRF activity in PP extracts from older rats. These data indicate that PP from 10d male rats contain a trypsin-sensitive nondopaminergic PIF. Peak PRF activity in the neonatal PP is reached between days 30 and 40, whereas anterior pituitary responsiveness to PRF is highest on day 20. These results suggest that a variable input from the PP, including PRF, dopamine and a nondopaminergic PIF, may be important for the maturation of the PRL-releasing mechanism during the postnatal development of the male rat.

ISSN:0028-3835    

DOI:10.1159/000125293

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The present study was designed to investigate the role of glucocorticoids in mediating the stimulatory effect of interleukin-1 (IL-1) upon the adrenocortical (AC) axis. Intact male rats were injected with either vehicle or dexamethasone (DEX) (5–50 µg/100 g b.w.) and were subsequently exposed to ether stress or to an intracerebroventricular (i.c.v.) injection of 2 U recombinant human IL-1β. In addition, adrenalectomized (ADX) rats were injected i.c.v. with 2U IL-1; for comparison ADX rats were also exposed to ether stress and insulin-induced hypoglycemia. In intact rats, ether-stress-induced AC activation was much more sensitive to the DEX inhibitory effect than the IL-1-induced AC activation. In ADX animals, insulin-induced hypoglycemia and ether stress produced a significant increase in ACTH serum values whereas IL-1 administration failed to activate ACTH secretion. Glucocorticoid binding studies showed that an i.c.v. injection of 2 U IL-1, 3 h before sacrifice, markedly reduced the specific in vitro binding of 3H-corticosterone by the nuclear fraction of dorsal hippocampal tissue slices. These results suggest that IL-1may activate the AC axis, at least in part, by interfering with the negative feedback effect of circulating glucocortico

ISSN:0028-3835    

DOI:10.1159/000125294

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The effect of norepinephrine on LH is complex: the ovarian steroidal milieu appears to determine whether norepinephrine stimulates or inhibits LH secretion. It has been proposed that steroids allow norepinephrine to have opposite effects on LH by altering the relative concentrations of α1-(stimulatory) and β-(inhibitory) adrenergic receptors in the hypothalamus. Thus, many investigators have argued that estradiol may permit norepinephrine to stimulate LH release by increasing the density of α1- and decreasing the density of β-adrenergic receptors in one or more key hypothalamic regions. To test this hypothesis specifically, we measured the density of β1- and β2-adrenergic receptor densities in proestrous, ovariectomized, and ovariectomized estradiol-treated rats at various times of day to determine (1) whether the densities of β-receptors exhibit diurnal rhythmicity, (2) whether β-receptors decrease during the time of increased LH secretion and/or (3) how steroidal milieu influences the density and/or the rhythm of receptor densities. The densities of β1- and β2-receptors exhibit a diurnal rhythm in some brain areas. These rhythms are detectable only in proestrous and ovariectomized rats and only in selected brain regions. Estrogen treatment has opposing effects in different brain regions. It suppresses the rhythm of β1-receptor concentrations in ovariectomized rats and also suppresses the average density of receptors in the suprachiasmatic nucleus and pineal gland. In contrast, estrogen increases the density of β1-receptors in the medial preoptic nucleus. In summary, the results of this study demonstrate that the diurnal rhythm in β-receptors and the effect of estradiol correlate with previously reported changes in receptor-mediated functions. In addition, they reveal the complex interactions of time of day and steroidal milieu on the density of β1- and β2-receptors in various brain regions. Finally, the data strongly suggest that decreases in the densities of β-receptors cannot explain the timing of the proestrous or estradiol-induced LH surge or the ability of norepinephrine to inhibit LH release in ovariectomized rats or stimulate LH release in stero

ISSN:0028-3835    

DOI:10.1159/000125295

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Because of the well-established reduction in the concentration of somatostatin in several brain areas of patients with histologically verified Alzheimer’s disease, we sought to determine if growth hormone (GH) secretion is altered in Alzheimer’s disease. In order to study this, we assessed the GH response to growth hormone releasing factor (GRF) in 8 patients with Alzheimer’s disease and 8 age-matched controls. Although there was no difference between the magnitude of the GRF-induced GH response (Δ max GH response or area under the curve) between the Alzheimer’s disease patients and the controls, the Alzheimer’s patients exhibited a delayed GH respo

ISSN:0028-3835    

DOI:10.1159/000125296

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Hyperprolactinemia suppresses endogenous prolactin (PRL) secretion and inhibits LH release in ovariectomized rats. Opiate peptides appear to mediate the suppressive effects of hyperprolactinemia on both endogenous PRL and LH secretion. A mechanism by which hyperprolactinemia may change the ability of opiates to influence PRL and LH is by altering the density of opiate receptors. We, therefore, examined the effect of hyperprolactinemia on the density of naloxone binding sites in hypothalamic regions that are important in the regulation of PRL and LH secretion. Female rats, ovariectomized for 4 days, were treated with ovine prolactin (oPRL) every 8 h for 2 days, and naloxone binding sites were measured using autoradiographic procedures. oPRL treatment suppressed the concentration of naloxone binding sites throughout the arcuate nucleus but had no effect in the median eminence, suprachiasmatic nucleus, and medial preoptic nucleus. There is evidence that the tuberoinfundibular dopaminergic neurons of the arcuate nucleus are directly influenced through opiate receptors. We propose that the observed decrease in the density of opiate receptors may occur on dopaminergic neurons. This theory provides an explanation for a mechanism for the suppression of endogenous PRL and LH by hyperprolactinemia: a decrease in opiate receptors will decrease opiate suppression of dopamine neurons allowing dopamine activity to increase. Increases in dopamine release are known to decrease PRL and LH secretion in ovariectomized rats. Alternatively, decreased naloxone binding may result from homologous down-regulation of receptors due to increased opiate activity. If opiate activity increases, it may directly inhibit LHRH neurons and may suppress the activity of inhibitory neurons leading to increased dopamine activity.

ISSN:0028-3835    

DOI:10.1159/000125297

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Stereoselective competition was used to determine (3H)-aldosterone binding to type I corticosteroid receptors, and (3H)-dexamethasone binding to type II receptors in punches obtained from 11 brain regions of short-term adrenalectomized (ADX) rats. It was observed that type I receptor binding was almost exclusive of the hippocampus (HIPPO), while type II receptor binding was more generally distributed among HIPPO, cerebral cortex, lateral septum, ventromedial and arcuate hypothalamic nuclei, with lower levels in 6 additional regions studied. We determined corticosterone (CORT) in brain punches from ADX rats, ADX rats receiving CORT for 5 days, intact rats and intact rats receiving ACTH for 5 days. We correlated (3H)-ligand binding with CORT content in punches obtained from identical brain regions and showed a significant positive correlation in the case of the ADX plus CORT group, for type II corticosteroid receptors. Similarly, a significant correlation emerged with type II sites, when binding capacity was correlated with percentage increases of CORT in brain areas of rats receiving ACTH. It is suggested that in situations where CORT levels are elevated, changes in CORT retention throughout the brain occur as a function of the type II glucocorticoid receptor, although at the level of the HIPPO, both receptors may provide appropriate control of the CNS-pituitary-adrenal axis, according to the physiological or stress levels of circulating hormone.

ISSN:0028-3835    

DOI:10.1159/000125298

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The in vitro effects of human growth hormone releasing factor (hGRF, 1–44) were studied in somatotroph-enriched cultures (75–85%) obtained from adult male rat pituitaries. Cells perifused with hGRF showed an up to 800% increase in growth hormone (GH) release over basal values in a dose-dependent manner. Calcium current Mockers (5 mM of Co2+, Ni2+ or Cd2+) completely inhibited this stimulating effect but sodium-free (choline) medium did not. Using a single-intracellular-electrode recording technique, it was found that hGRF induced a dose-dependent depolarizing response concomitant with a decrease in membrane resistance in 38% of the cells recorded (98 of 258 cells). The reversal potential of this response was close to –40 mV. This depolarizing response was recorded in both excitable and unexcitable cells with no marked difference. Co2+ and Ni2+ (5 mM) completely and reversibly inhibited the membrane response to hGRF. Application of hGRF and somatostatin (SRIF), a hormone that inhibits GH release, to the same cell cultures showed the existence of two subpopulations: one was responsive to both hGRF and SRIF (53%, n = 62), another was only responsive to SRIF (47%, n = 62). Human GRF did not affect prolactin release and did not modify the electrical properties of cells responding to dopamine and therefore considered as lactotrophs. These results suggest that (1) hGRF leads to an increase in growth hormone release and a modification of membrane electrical properties by means of an extracellular Ca2+-dependent pathway, and (2) according to their responses to SRIF and hGRF, there are at least two subpopulations of somatot

ISSN:0028-3835    

DOI:10.1159/000125299

出版商:S. Karger AG    

年代:1989

数据来源: Karger