摘要:

In this paper, by means of a push-pull perfusion technique, we have examined the local effect of ovine prolactin (oPRL) on the spontaneous in vivo dopaminergic (DAergic) activity of the nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) of living male rats. First, we found a 2-fold spontaneous rise of 3,4-dihydroxyphenylacetic acid (DOPAC) output during the afternoon hours of the photoperiod only in the NAcc. In addition, native oPRL (10 ng/µl for 20 min), but not boiled oPRL, locally perfused into the NAcc caused a significant elevation in DOPAC output without changes in homovanillic acid or 5-hydroxyindoleacetic acid. In a similar preparation, male rats bearing push-pull cannulae in the SN or VTA were infused locally with oPRL (10 or 50 ng/µl) for 20 min. The hormone did not alter the efflux of DOPAC from these DA cell body/dendrite areas. These results indicate that oPRL can activate the mesolimbic DA system through local actions on DA presynaptic terminals of the NAcc without affecting the SN or VT

ISSN:0028-3835    

DOI:10.1159/000125031

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The relationship of opiate receptors in the medial preoptic area of the hypothalamus (MPOA) to the gonadal steroid hormone environment during development was assessed using regional densitometric analyses of [3H]naloxone binding in autoradiographs prepared using brain sections from 5-day-old male and female rats treated postnatally either with tamoxifen (0.5 mg/kg), flutamide (20 mg/kg), dihydrotestosterone (DHT; 12.5 mg/kg), or sesame oil vehicle. Tamoxifen, a specific estrogen receptor antagonist, did not alter MPOA binding density in either males or females. Flutamide, a specific androgen receptor antagonist, and DHT, a nonaromatizable androgenic compound, altered the MPOA binding density in males and females, respectively. No treatment altered the binding density in several other brain regions. The results suggest that androgen, not estrogen, regulates the differentiation of MPOA opiate receptors. Since the neuronal development in the region is thought to be mediated by estrogen, both hormones probably act concurrently to affect the ontogeny of different parameters in the same brain region.

ISSN:0028-3835    

DOI:10.1159/000125032

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

A series of experiments was performed to monitor plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin responses to human gonadotropin-releasing hormone (GnRH) associated peptide (GAP) and related peptides. Ovariectomized hypothalamo-pituitary disconnected (HPD)ewes were challenged with injections (1–10 µg i.v.) of GAP, or given, with and without estradiol, hourly 500- or 1,000-ng pulses of GAP for 5–7 days. In all cases GAP failed to cause the release of LH or FSH from the pituitary gland or to alter mean plasma prolactin concentrations. When the same HPD ewes were given hourly or 2-hourly pulses of 250 ng GnRH, LH responded in a pulsatile manner, and FSH secretion was maintained, thus confirming the functional integrity of the pituitary gland after HPD. Fragments of the GAP molecule (pro-GnRH 14–36, 28–36, 38–49, and 51–66) and GAP dimer did not stimulate LH or FSH or inhibit prolactin release in HPD ewes. GAP and GAP dimer did not affect pituitary responsiveness to GnRH administration. GAP also failed to inhibit the thyrotropin-releasing hormone-induced rise in prolactin. Finally, GAP injections (100 µg i.v.) given to lactating ewes did not cause any change in plasma prolactin concentrations. These data show that human GAP, GAP dimer, or putative processed GAP peptides do not act on the sheep pituitary gland in a variety of physiological states to regulate gonadotropin or prolac

ISSN:0028-3835    

DOI:10.1159/000125033

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Previous reports suggest that Al noradrenergic projections to the hypothalamus may have stimulatory or inhibitory effects on the release of luteinizing hormone releasing hormone (LH-RH), depending upon the steroid environment of the rat. In the present study, we reevaluated the effects of electrical stimulation (ES) of the Al cell group on LH release in estrogen-primed, ovariectomized rats which had been anesthetized with chloral hydrate. This anesthetic blocked spontaneous LH surges which normally occur in estrogen-treated ovariectomized rats. ES of the Al cell group in chloral hydrate treated rats failed to alter basal LH concentrations. Therefore, we evaluated the effects of Al-ES on LH release in rats in which prior electrochemical stimulation (ECS) of the medial preoptic nucleus (MPN) was performed. Bilateral MPN-ECS induced a significant increase in plasma LH. When the Al cell group was unilaterally stimulated (1 mA) for 15 min, beginning 30 min after MPN-ECS, peak LH concentrations were significantly augmented with peak values being reached at 60 min. Thereafter, plasma LH declined from 75 to 180 min towards basal levels. In a second experiment, unilateral MPN-ECS was performed, and 30 min later either the ipsilateral or contralateral Al cell group was ES. When MPN + A1 were stimulated on the ipsilateral side of the brain, no amplification in LH release occurred above that obtained after only MPN-ECS. In contrast, contralateral Al-ES markedly amplified LH release, suggesting that most stimulatory Al fibers decussate to reach contralateral LH-RH neurons. Moreover, in rats which received contralateral MPN + A1 stimulation (0.1 mA), plasma LH reached peak concentrations and then remained significantly higher than in controls (MPN-ECS group) throughout the rest of the experiment. In the third experiment, we evaluated the effects of drugs which affect norepinephrine synthesis or are antagonists of beta or alpha adrenoreceptors. Diethyldithiocarbamate, a dopamine-β-hydroxylase inhibitor, and phenoxybenzamine, an alpha adrenoreceptor antagonist, completely blocked Al-ES-induced amplification of LH release. Propranolol, a beta adrenoreceptor antagonist, did not suppress the effects of Al stimulation on LH secretion. None of these drugs had any appreciable effect on the patterns or concentrations of LH which were released by MPN-ECS. We conclude that LH release can be amplified following Al-ES, but only after preliminary depolarization of LH-RH neurons. We also provide evidence that the major stimulatory Al projections decussate to enter contralateral hypothalamic regions which contain LH-RH neurons. Finally, our pharmacological data suggest that the principal neurotransmitter involved in amplifying LH release may be either norepinephrine or epinephrine as an alpha but not a beta adrenoreceptor antagonist completely blocks the response of LH-RH neurons to Al-ES

ISSN:0028-3835    

DOI:10.1159/000125034

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

This study compares the selective effect of androgens on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release induced either by LH-releasing hormone (LH-RH) or by protein kinase C activation in rat anterior pituitary cells in culture. In control cells, phorbol-12-myristate-13-acetate (PMA) stimulated the release of radioimmunoassayable LH and FSH in a dose-dependent manner at an ED50 value of 5.95 ± 1.45 nM. The maximal release of gonadotropins induced during a 3-hour incubation with PMA was 40–60% of that induced by LH-RH. Preincubation of the cells for 2–4 days with 10 nM 5α-dihydrotestosterone (DHT) decreased by approximately 60% the subsequent release of LH induced by 100 nM LH-RH or by 500 nM PMA during a subsequent 3-hour incubation. The inhibitory effect of DHT was completely suppressed by coincubation with the antiandrogen hydroxyflutamide. DHT exerted a similar inhibitory effect on LH release induced by another stimulator of protein kinase C activity, namely 1-oleoyl-2-acetylglycerol. The potent inhibitory action of DHT on LH-RH- or PMA-induced LH release was exerted at an ED50 value of approximately 10 pM. Contrary to the effect on LH, the FSH response to LH-RH or to PMA was increased by preincubation with 2 nM DHT, the stimulatory effect of the androgen being completely antagonized by hydroxyflutamide. The present data show that the characteristics of the selective and differential action of androgens on LH and FSH release are identical following stimulation by LH-RH or by protein kinase C activation. Such data suggest that the direct feedback action of androgens in pituitary gonadotrophs is exerted at post-LH-RH receptor sites which may involve protein kinase C itself and/or biochemical events induced by the e

ISSN:0028-3835    

DOI:10.1159/000125035

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The neuroendocrine function is regulated by several neurotransmitters (acetylcholine, dopamine, somatostatin and noradrenaline) known to be reduced in brains of patients with Alzheimer’s disease (AD). Moreover, the hypothalamus also has pathological changes. In spite of these findings suggesting neuroendocrine dysfunctions, this function has seldom been investigated in AD patients so far. We have compared patients with clinically ‘probable’ AD of mild-to-moderate severity with nondemented age- and sex-matched controls. Plasma levels of prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone (TSH) were measured by commercially available radioimmunoassays (RIA) before and after stimulation with metoclopramide, /-dopa or thyrotropin-releasing hormone. Basal plasma levels of β-endorphin and β-lipotropin were measured by RIA after high-performance liquid chromatography. Basal and stimulated plasma levels of PRL, GH, TSH and β-lipotropin were similar in the two groups. Basal plasma levels of β-endorphin were significantly higher in the patient group. Of doubtful clinical importance, this might be attributed to decreased tuberoinfundibular dopaminergic activity and has also been seen in patients with Parkinson

ISSN:0028-3835    

DOI:10.1159/000125036

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The suprachiasmatic nuclei (SCN) have been implicated as neural timers of reproductive events and as possible sites of action for melatonin. We tested the hypothesis that ablation of the SCN (SCNx) would counteract the inhibitory effect of exogenous melatonin on blastocyst implantation in the spotted skunk by removing a possible site of action. Thirty-eight pregnant females with unimplanted blastocysts were treated as follows: 4 served as untreated controls, 6 received empty Silastic capsules, 5 received Silastic capsules containing melatonin, 10 received sham lesions in the SCN, 7 received lesions in the SCN and Silastic capsules containing melatonin, and 6 received lesions in the SCN and empty Silastic capsules. All surgical treatments were completed by February 15. The skunks were subjected to a natural photoperiod, and the duration of preimplantation was measured. The lesions destroyed an average of 87 ± 10% of the SCN and a small amount of the surrounding hypothalamus. SCNx had no significant effect on duration of preimplantation (200 ± 25.6 days) when compared to sham SCNx (205 ± 21.5 days). Melatonin significantly (p < 0.05) lengthened the duration of preimplantation in both intact (277 ± 59 days) and SCNx (265 ± 64.7 days) skunks when compared to all other groups. These data are not consistent with the hypothesis that the SCN are required for melatonin to exert its influence on timing of implantation in the spotted s

ISSN:0028-3835    

DOI:10.1159/000125037

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We have developed RIAs using antisera directed against the cryptic peptide of the GnRH precursor (termed GnRH-associated peptide, GAP) and have used these together with a GnRH assay to characterize proGnRH-derived peptides in rat hypothalamic extracts. On Sephadex chromatography we have identified three molecular forms of GAP-like immunoreactivity (GAP-LI), in addition to the GnRH decapeptide. The largest of these forms is an 8.0-kilodalton (kD) GAP-LI which appears to be the complete proGnRH peptide. The second is a 6.5-kD GAP-LI, and is similar to the complete cryptic peptide (i.e. proGnRH14–69 or GAP1–56). The third peptide is a 2.5 kD C-terminal fragment of the cryptic peptide, representing a processed form of GAP. In whole hypothalamic extracts from normal rats the 8.0-kD form was the major form, comprising 60–70% of the total GAP-LI. All three forms were present in three distinct areas of the rat hypothalamus, namely median eminence (ME), anterior and mid-hypothalamus. However in the ME the proportion of 8.0-kD GAP-LI was significantly reduced and the proportion of 6.5-kD GAP-LI significantly increased compared to anterior and mid-hypothalamic samples (p < 0.05). In whole hypothalamic extracts from pregnant and lactating rats the total content of proGnRH-derived peptides was reduced but the relative proportions of these peptides were not significantly changed from normal female rats. However in postlactating rats, 2 weeks after removal of pups, the total levels of GAP-LI were unchanged compared to normals, but the percentage of 8.0-kD GAP-LI was significantly decreased and the percentage of 2.5-kD GAP-LI significantly increased compared to normals (p < 0.05), suggesting that proGnRH may undergo additional processing dependent on physiological condition. In fetal and neonatal rats the proportion of the 6.5-kD peptide was increased and that of the 8.0-kD peptide decreased compared to adults, and this change became less significant with increasing age. In ovariectomized rats the proportion of 6.5-kD GAP-LI was increased and that of 8.0-kD GAP-LI decreased; this change was partially reversed with steroid treatment. Both the 6.5 and 2.5-kD forms were released by high K+ stimulation of neonatal hypothalamic cells in culture. These results indicate that there is differential processing of the proGnRH precursor within the hypothalamus and in altered physiological s

ISSN:0028-3835    

DOI:10.1159/000125038

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Using a recently developed model for investigating the neuroendocrine role of melatonin in man, we studied melatonin’s effect on the nocturnal secretion of thyrotropin and cortisol in 17 normal male volunteers. The model consists of sleep in the dark and all-night sleep deprivation in conditions of: bright light with and without a melatonin infusion, and dim light. We have improved our infusion paradigm so that levels of melatonin during infusion are now indistinguishable from those occurring during sleep in the dark or dim light sleep deprivation. Sleep deprivation per se raised TSH levels compared to normal sleep. However, the three conditions of sleep deprivation could not be distinguished from each other, which suggests that the suppression of TSH by sleep (or the stimulation of TSH by sleep deprivation) is not mediated by melatonin. Cortisol secretion was unaffected by sleep deprivation regardless of melatonin’s presence or absence. However, a difference in the pattern of secretion of cortisol in the sleep condition in the early morning (compared to the sleep deprivation conditions) was noted. These data do not implicate melatonin in the acute regulation of TSH or cortisol in normal man. These data also provide a method of melatonin infusion that replicates the pattern and levels seen in sl

ISSN:0028-3835    

DOI:10.1159/000125039

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We have previously observed that gonadal steroid treatments, which stimulate a proestrous-like LH surge in ovariectomized rats, cause a marked reduction in the responsiveness to opiates of a variety of CNS processes. The present study was undertaken to determine if a similar decline in opiate responses is associated with the endogenous steroid-induced LH surge on the afternoon of proestrous. Rats were evaluated for thermic, nociceptive, behavioral and LH secretory responses to morphine sulfate on diestrous I afternoon (DiPM) and proestrous morning (ProAM), times at which LH secretion is low, as well as on proestrous afternoon (ProPM) during the preovulatory LH surge. While on DiPM and ProAM, morphine caused a 33–45% reduction in serum LH levels at doses as low as 5 mg/kg b.w., in ProPM rats doses as high as 10 mg/kg did not affect LH secretion. Similarly, ProAM rats showed a prompt and sustained analgesic response to morphine, but ProPM rats showed a delayed response of shorter duration. DiPM rats showed an acute response intermediate to that of ProAM and ProPM animals. While DiPM and ProAM rats exhibited the expected hypothermic response to a high dose of morphine (15 mg/kg), ProPM rats showed no decline in core body temperature, but exhibited a delayed hyperthermic response to the opiate. DiPM and ProAM rats showed a dose-dependent decline in locomotor behavior in response to morphine. In contrast, ProPM rats, which exhibited a significantly elevated basal locomotor activity, failed to show a reduction in locomotion after morphine treatment. Collectively, these data indicate that a generalized alteration in opiate responsiveness occurs on the afternoon of proestrus. This change in CNS opiate-receptor mechanisms may play a role in the plethora of physiologic alterations which accompany the preovulatory LH surge on proestru

ISSN:0028-3835    

DOI:10.1159/000125040

出版商:S. Karger AG    

年代:1988

数据来源: Karger