摘要:

We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6–7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (3H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (≈ 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laborat

ISSN:0028-3835    

DOI:10.1159/000124997

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

When fetal preoptic area (POA) brain grafts that contain gonadotropin-releasing hormone cells are transplanted into the third ventricle of adult female hypogonadal mice, the animals respond with sexual maturation, persistent estrus, and the ability to ovulate reflexively after mating. However, the absence of normal spontaneous ovulatory cyclicity suggests an impairment in positive feedback. We, therefore, studied the effect of administration of progesterone alone or of sequential estradiol benzoate and progesterone on plasma levels of luteinizing hormone (LH) in groups of hypogonadal (HPG) mice in persistent estrus after receiving POA grafts (HPG/POA). Individual differences in responsivity to progesterone were related in part to the length of time in persistent estrus. Approximately 30% of HPG/POA grafts tested 2 months after graft showed increased levels of plasma LH. This was reduced to 10% when animals were tested 5 months after graft. Sequential administration of estradiol benzoate plus progesterone to intact HPG/POA mice was ineffective in elevating LH. The presence of corpora lutea in ovaries verified that only animals with a progesterone induced LH surge ovulated. Other HPG/POA mice were mated, and the occurrence of reflex ovulation was determined. Four of these mice delivered pups: 3 were previous responders to progesterone. One female mated again during the immediate postpartum period and delivered a second litter. Following weaning of all offspring, this animal displayed spontaneous ovarian cyclicity, confirmed by ovarian histology. This is the first proven example of spontaneous ovulation in a mutant mouse with a brain graft. The results show that some HPG/POA mice are capable of positive feedback responses, and rarely, of becoming spontaneous ovulators.

ISSN:0028-3835    

DOI:10.1159/000124998

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

During the induction of lordosis responses in golden hamsters, the joint actions of estradiol (E) and progesterone (P) have been found to produce major changes in the activity levels, sensory responsiveness and movement-related firing of neurons in the dorsal midbrain, a region vital for lordosis in this species. The present study investigated the possibility that these effects of E and P on dorsal midbrain neurons might arise through changes in transsynaptic excitability or spike-generating processes. Single dorsal midbrain neurons were orthodromically or antidromically activated by ventromedial midbrain tegmental stimulation in ovariectomized, urethane-anesthetized hamsters before and after subcutaneous injection of P in propylene glycol vehicle. P injection produced two neurophysiological effects: (1) a strong depression of transsynaptic activation, and (2) in antidromically invaded neurons, a change in the amplitude (either an increase or decrease) of the soma-dendritic spike component. Both of these effects appeared rapidly (i.e. within 10–20 min) after P injection. The P effect on orthodromic neuronal excitability was contingent upon E priming of the hamsters, but, in contrast, the P effect on antidromic spike amplitude was not. Several features of these neurophysiological effects of P imply that the hormone may have been acting through nongenomic mechanisms, possibly involving receptors in neuronal membrane

ISSN:0028-3835    

DOI:10.1159/000124999

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Previous studies have suggested that gamma-aminobutyric acid (GABA) exerts inhibitory actions on luteinizing hormone (LH) secretion that are likely to be mediated by modifications in noradrenergic transmission. To explore further this hypothesis we have studied the effect of increasing GABA contents in discrete areas of the brain on plasma LH levels in short-term orchidectomized rats. GABA accumulation was produced by the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG). The locus coeruleus area (LC), where the noradrenaline (NA) cells projecting through the dorsal noradrenergic bundle are located, and several hypothalamic areas that are innervated by NA-containing fibers were microinjected with GVG. Most of these areas are known to be related to the neural control of LH secretion. GVG microinjected in the LC and medial preoptic area increased the GABA content and blunted significantly the acute increase of plasma LH produced by castration. Bicuculline prevented these effects. Delayed effects of GVG were observed when applied in the anterior hypothalamic area and ventromedial-arcuate nucleus area. In these latter areas, a single injection of GVG did not augment the GABA concentrations and was unable to prevent LH release, but a clear inhibitory effect took place after a second injection of GVG between 24 and 48 h after orchidectomy. Unresponsive areas to GVG treatment were the lateral preoptic area, the median eminence and the dorsal raphe. These results add support to the view that GABA inhibits LH release in rats, at discrete areas of the brain.

ISSN:0028-3835    

DOI:10.1159/000125000

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The number of gonadotropin-releasing hormone (GnRH) receptors is known to vary throughout the estrous cycle and in other endocrine states in the rat. These changes in receptors parallel closely the concentrations of serum estradiol during the cycle. In the present study, we used two different cytochemical techniques to determine if changes in GnRH receptors represented alterations in the number of GnRH-receptive cells. Furthermore, we tested the effects of estradiol pretreatment on this phenomenon. Dispersed pituitary monolayers taken at different stages of the cycle were stimulated for 3 min with 1 nM biotinylated [D-lys6]-GnRH (bio-GnRH) which was localized using the avidin-biotin-peroxidase complex (ABC) technique and a black peroxidase substrate. Parallel groups were stained, while living, with an avidin-fluorescein conjugate. Some monolayers were pretreated with physiological concentrations of estradiol benzoate (1 nM – 1 pM) prior to bio-GnRH exposure and ABC stains. The resulting stains demonstrated that the percentage of bio-GnRH-receptive cells was 2–3 times greater at 10.00 h proestrus (20.2 ± 4%) when compared to the same time in estrus (8.7 ± 2%), diestrus I (5.2 ± 0.5%), diestrus II (7.6 ± 1%), and at 17.00 h diestrus II (11.4 ± 0.9%) and proestrus (7.4 ± 0.8%). These data correlated well with those obtained from living gonadotropes stained with avidin-fluorescein. Estradiol exerted a biphasic effect dependent upon the stage of the cycle at which the cells were taken.Estradiol (1 pM) treatment of monolayers taken at 10.00 h diestrus I and II increased the percentage of GnRH-receptive cells to that normally observed at 17.00 h diestrus II (11.01 ± 1.5 and 11.9 ± 1%, respectively). However, the same concentration of steroid reduced the number of GnRH-receptive cells taken at 10.00 h proestrus to levels normally observed at diestrus I (6.4 ± 0.7%). These results indicate that changes in GnRH receptors during the estrous cycle represent fluctuations in the percentage of GnRH-bound cells, and that circulating levels of estradiol can mediate this change in number. It is suggested that the recruitment of GnRH-receptive cells, in conjunction with increases in both total and multihormonal gonadotropes, prepares these cells to support the preovulatory gonado

ISSN:0028-3835    

DOI:10.1159/000125001

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The purpose of the present study was to determine whether gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus of the prepubertal monkey may be prematurely provoked into producing a sustained train of intermittent GnRH release. N-methyl-DL-aspartic acid (NMA), an analog of the putative excitatory neurotransmitter aspartate, was used to stimulate the hypothalamus. In order to utilize pituitary luteinizing hormone (LH) secretion as a bioassay of hypothalamic GnRH release, juvenile males were castrated and the responsiveness of their gonadotrophs to GnRH was enhanced prior to the study with a chronic intermittent intravenous infusion of the synthetic decapeptide (0.1 µg/min for 3 min every hour). Treatment with this regimen of GnRH, which appears to provide the pituitary gonadotrophs with a hypophysiotropic stimulus similar to that produced by the hypothalamus of castrated adults, elicited a pattern of pulsatile LH secretion in prepubertal animals similar to that observed in the open-loop situation in adults. This episodic pattern of LH release was sustained without decrement following termination of GnRH priming and initiation of an intermittent intravenous infusion of NMA (4.5–6.5 mg NMA/kg body weight/pulse, administered over 1 min) delivered at a frequency of 1 pulse/1 h for 50 h. In contrast, an intermittent infusion of the vehicle employed to administer NMA (saline) failed to maintain LH secretion. Administration of the same dose of NMA at a slower frequency of 1 pulse/2 h for 52 h, while also sustaining LH secretion without decrement, resulted in an exaggeration in the LH response. Since it has been previously established that NMA-induced release of LH is mediated by hypothalamic GnRH, these results demonstrate that in the monkey GnRH neurons possess the potential for sustaining an adult-like pattern of intermittent GnRH release well before the onset of puberty. The foregoing findings are discussed in the context of current understanding of the neuroendocrine mechanisms underlying the prepubertal hiatus in gonadotropin secretion in primat

ISSN:0028-3835    

DOI:10.1159/000125002

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We explored whether endogenous TRH in the hypothalamus produced a potential change in its receptors in the rat anterior pituitary. Thyroidectomy caused a progressive increase in the pituitary TRH binding with a concomitant increase in the blood TSH level. Injection of T4 prevented the increase in the pituitary TRH binding and the blood TSH level after thyroidectomy. The hypothalamic deafferentation and electrolytic lesions in the hypothalamic paraventricular nuclei led to a significant reduction in both the content of TRH in the hypothalamic median eminence and the blood TSH level, but they affected neither the number nor affinity constant of the pituitary TRH receptors in thyroidectomized rats. The present data provide evidence that TRH receptors in the anterior pituitary are profoundly regulated by thyroid hormones, but not significantly by TRH in the hypothalamus in the rat.

ISSN:0028-3835    

DOI:10.1159/000125003

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The pituitary-adrenal axis is known to be stimulated during the acute-phase response. As cytokines play a central role in mediating the constellation of host response occurring during the acute-phase response it was of interest to assess the ability of cytokines to stimulate ACTH secretion from normal pituitary cells in culture. We used human recombinant interleukin-1β and -α (hrlL1β, hrlL1α) and human recombinant tumor necrosis factor α (hrTNFα) to analyze the ability of these cytokines to induce ACTH secretion from normal rat anterior pituitary cells in culture. We also investigated the possible roles of prostaglandin E2 (PGE2) and cAMP in the cellular transduction mechanism. After 3 days of incubation primary cultures of rat anterior pituitary cells were stimulated for 24 h with either hrlL1β, hrlL1α or hrTNFα alone or with the addition of dexamethasone or indomethacin. The culture media were analyzed for ACTH, PGE2 and cAMP content. At doses ranging from 0.03 to 30 nM, hrlL1β stimulated the release of ACTH and PGE2 in a dose-dependent manner. In contrast, at doses ranging from 3 to 60 nM, hrTNFα was unable to stimulate ACTH secretion although it stimulated PGE2 synthesis. Time-course experiments demonstrated that hrlL1β (3 nM) stimulates ACTH production over a period of 8, 16 and 24 h, but not after a period of 4 h. In these experiments, hrlL1β failed to cause any change in the secretions of growth hormone and luteinizing hormone. In hrlL1β-stimulated cells, indomethacin (10 mM) completely inhibited PGE2 production without significantly affecting ACTH release, whereas dexamethasone (50 nM), which also inhibited PGE2 production, partially inhibited ACTH secretion. Finally indomethacin blocked the hrlL1β-induced cAMP accumulation obtained after 24 h, without significantly affecting hrlL1β-induced ACTH release. The results obtained with hrlL1α were similar to those obtained with hrlL1β. In conclusion, although hrlL1β, hrlL1α and hrTNFα stimulate PGE2 synthesis, only hrlL1β and hrlL1α stimulate ACTH release from normal rat anterior pituitary cells in culture. The stimulation is partially inhibited by dexamethasone and the cellular transduction mechanism involved in this ACTH release does not depend on PGE2 or cAMP. These results confirm the interaction between the endocrine and the immune systems. They suggest that the monokine-induced stimulation of the pituitary-adrenal axis may represent a potent negative feedback mechanism through which the immune system avoids an overshoot of the inflammatory and febrile effect stimulated during th

ISSN:0028-3835    

DOI:10.1159/000125004

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

It has been shown that histamine (HA) stimulates prolactin (PRL) secretion via H2 receptors following intra-cerebroventricular infusion and via Hi receptors following systemic (intra-arterial) infusion. Since the effect of HA appears to be exerted at a suprapituitary level, we investigated the involvement of the tuberoinfundibular dopaminergic (TIDA) system in HA-induced PRL secretion in urethane-anesthetized male rats. HA infused intracerebroventricularly (30 µg) or intra-arterially (420 µg) decreased the dopamine (DA) concentration in pituitary portal blood by 30 and 23%, respectively. Blockade of DA receptors by pimozide did not prevent the stimulation of PRL secretion induced by intracere-broventricular infusion of HA or the H2 receptor agonist dimaprit. Furthermore, during DA receptor blockade intracere-broventricular infusion of the H1 receptor agonist 2-thiazolylethylamine inhibited PRL secretion. In contrast, pimozide prevented the stimulation of PRL secretion induced by intra-arterial infusion of HA and the H1 receptor agonist 2-thiazolylethylamine. In fact, under these conditions intra-arterial infusion of HA or the H2-receptor agonist dimaprit inhibited PRL secretion. During treatment with α-methyl-p-tyrosine, which reduced the hypothalamic DA content by 50%, HA infused intracerebroventricularly stimulated PRL secretion, while HA infused intra-arterially inhibited the secretion, which is in accordance with the results obtained during pimozide treatment. Cholinergic blockade by atropine did not prevent the HA-induced PRL release, exluding the possibility that the observed effect of pimozide is due to its anticholinergic property. We suggest that intracerebroventricular infusion of HA by activation of H2 receptors may stimulate PRL secretion partly via inhibition of the TIDA system and partly via other mechanisms. Furthermore, by activation of H1 receptors, intracerebroventricularly infused HA seems to inhibit PRL secretion by a DA-independent mechanism. In contrast, intra-arterial infusion of HA may by activation of H1 receptors stimulate PRL secretion preferentially via inhibition of the TIDA system, while the H2 receptor mediated PRL-inhibiting effect of intra-arterially infused HA may be related to other mechanis

ISSN:0028-3835    

DOI:10.1159/000125005

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Cortisol administered at a dose of 25 mg/kg 24 h before measurements decreased the prolactin secretion induced by intraventricularly given opioids (dynorphin, beta-endorphin, Met-enkephalin or D-Met-Pro-enkephalin-amide). The effect of cortisol was depressed by actinomycin D pretreatment. The cortisol-induced inhibition of the action of morphine was facilitated in adrenalectomized animals; measuring the effects of increasing doses of cortisol a maximal inhibition was obtained at a dose of 5 mg/kg. The opioid-induced corticosterone secretion was not affected 24 h after a single administration of cortisol. The present results show that the cortisol-induced inhibition of opioid-induced prolactin secretion is dependent on protein synthesis and independent of changes in drug metabolism, and of the type of opiate receptor preferentially affected by the opiate agonists employed.

ISSN:0028-3835    

DOI:10.1159/000125006

出版商:S. Karger AG    

年代:1988

数据来源: Karger