摘要:

Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10–7M GHRH elicited a significantly lower GH secretion from the pituitaries of lean and obese female rats. In these pituitaries of obese male rats, but induced a similar GH secretion from the pituitaries, GH concentration was similar in obese versus lean male and female rats. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-1) were evaluated. Obese male rats had lower IGF-1 concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes. Determination of GHRH mRNA in the hypothalamus of obese rats showed that it was significantly reduced in male but not in female obese rats versus lean counterparts. In contrast, somatostatin mRNA concentrations were unchanged in the hypothalamus of obese rats of both sexes. Overall these data suggest that despite an in vivo reduced GH secretion, the hypothalamo-pituitary GH regulatory system is more preserved in female than in male obese rat

ISSN:0028-3835    

DOI:10.1159/000126455

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The number of axosomatic synapses, the length of the synaptic plates and the perimeter of the post synaptic neuronal perikarya were assessed on thin sections from the infundibular hypothalamic nucleus and from the ventrobasal thalamus of 3 adult ovariectomized African green monkeys that were treated with estradiol valerate and of 3 control animals that were injected with vehicle. Estradiol valerate treatment resulted in a 39% decrease in the number of axosomatic synapses in the infundibular hypothalamic nucleus. The length of the synaptic plates and the perimeter of the postsynaptic cells were not affected by the hormonal treatment. The decrease in the number of axosomatic synaptic inputs in the infundibular hypothalamic nucleus was accompanied by a significant increase in the glial ensheathing of neuronal somas. No effect of the hormonal treatment was detected in the ventrobasal thalamus. The results indicate that estrogen may induce glial and synaptic plasticity in the hypothalamus of adult primates.

ISSN:0028-3835    

DOI:10.1159/000126456

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In experiment I we studied the capacity of progesterone (P) and two nonsteroidal agents that activate lordosis, but do not bind to the progestin receptor (PR), i.e. luteinizing hormone-releasing hormone (LHRH) and prostaglandin E2 (PGE2) to induce sequential inhibition (SI) in ovariectomized estradiol-primed rats. The administration of 1 mg P, 5 µg LHRH or 100 µg PGE2 induced significant lordosis within 4 h. An injection of 1 mg P, 24 h after the administration of the above lordogenic agents, induced significant lordosis in rats pretreated with LHRH or PGE2, but not in those pretreated with P. Thus, only P induced SI (p < 0.025). In experiment II we investigated if progestin-induced SI results in a reduced capacity of the subjects to respond only to P or to other lordogenic agents. The synthetic progestin norgestrel (400 µg administered 24 h earlier) significantly reduced the responsiveness to P (p < 0.01), LHRH (p < 0.01), PGE2 (p < 0.025) and dibutyryl cyclic AMP (db cAMP p < 0.01). Results suggest that SI is triggered only by agents that bind to the PR (experiment I) and that it decreases the responsiveness of rats not only to P but also to other lordogenic agents (experiment I

ISSN:0028-3835    

DOI:10.1159/000126457

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Levels of serotonin (5-HT) and metabolite, 5-hydroxyindole-acetic acid (5-HIAA), dopamine and metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and norepinephrine (NE) were measured in microdissected brain areas at 14.30 and 19.30 h on diestrus and proestrus in rats. Lordosis, sexual behavior, was exhibited only by proestrous females at 19.30 h. The content of monoamines and/or metabolites changed from afternoon to early evening of diestrus in a number of brain regions. On proestrus, during the time when females became sexually receptive, additional changes appeared and many diestrous changes were reversed or amplified. Proestrus-specific changes were found in areas provinding the descending circuit for regulation of lordosis, the medial preoptic nucleus (mPOA), ventromedial nucleus of the hypothalamus (VMN) and midbrain central gray (MCG), and in areas outside of endocrine control centers such as parietal cortex (Ctx) and dorsal raphe nucleus (DR). Thus, these data are consistent with previous studies showing functional changes in monoaminergic transmitters during the day/night cycle and during hormonal induction of neuroendocrine events. NE levels increased between 14.30 and 19.30 h on proestrus in most brain areas, ranging from 20% increases in mPOA and Ctx to a 220% increase in the DR. NE levels decreased on proestrus in the VMN. The direction of proestrous changes in NE were reversed in some, but not all of the areas, between the afternoon and evening of diestrus. Dopamine was detectable in all areas sampled, and the metabolites HVA and DOPAC were detectable in some but not all areas. In the mPOA, DOPAC increased 100% during proestrus but was unchanged during the same period on diestrus suggesting a facilitatory effect of dopamine on lordosis in this area. Dopamine terminals in the MCG may inhibit behavior since HVA increased 150% between 14.30 and 19.30 h on diestrus and decreased 40% during the same interval on proestrus. For the serotonergic system, 5-HIAA levels increased 45% in the mPOA and 200% in the MCG from the afternoon to evening of proestrus but did not change on diestrus. In the VMN, 5-HIAA increased 60% between 14.30 and 19.30 h on diestrus but did not change during the same time on proestrus. 5-HIAA also increased 580% in the DR nucleus and 70% in the Ctx during proestrus but not diestrus. These data are consistent with previous studies suggesting that 5-HT terminals regulate lordosis responding on proestrus through hormone-dependent modulations at both facilitatory and inhibitory sites. In the VMN, where 5-HT inhibits lordosis, gonadal hormones appear to decrease the availability of 5-HT, and in the mPOA and MCG, where 5-HT may facilitate lordosis, gonadal hormones appear to increase the availability of 5-HT.

ISSN:0028-3835    

DOI:10.1159/000126458

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Nitric oxide (NO) is the endothelium-derived relaxing factor, which causes relaxation of vascular smooth muscle. NO synthetase, the enzyme for the synthesis of NO from its precursor L-arginine, is also widely distributed in neurons in the brain, and it has been suggested that NO may serve as an important neuromodulator. Because NO synthetase is present in the hypothalamus in relatively high concentration, we have determined whether NO can affect the release of vasopressin in conscious, chronically prepared rats. The intra-cerebroventricular (i.c.v.) injection of S-nitroso-N-acetylpenicillamine (12.5 and 25 µg; SNAP), that spontaneously breaks down to form NO, caused transient dose-related increases in the plasma vasopressin concentration of 1 and 2 µU/ml (p < 0.01), respectively. In control experiments in which N-ace-tylpenicillamine (25 µg), the precursor for the preparation of SNAP, was injected i.c.v. there was a small, 0.4 µU/ml, increase (p < 0.01) in the plasma vasopressin level. The i.c.v. injection of L-arginine (0.5 and 1 mg), also the precursor for the biosynthesis of NO, resulted in dose-dependent increases in the plasma vasopressin concentration similar in magnitude to those caused by SNAP. When D-arginine (1 mg), which cannot serve as a substrate for NO synthetase, was injected i.c.v., there was only a slight delayed increase in the plasma vasopressin concentration. Thus, NO can act centrally to stimulate vasopressin release and may serve as a neuromodulator in the control of vasopressin rele

ISSN:0028-3835    

DOI:10.1159/000126459

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Amino acid concentration in the anterior preoptic area and medial basal hypothalamus was determined by HPLC in female rats: (1) at 16 (prepubertal) vs. 30 (peripubertal) days of age and (2) after N-methyl-D-aspartate (NMDA) or dizocilpine (MK-801) administration in both groups. 30-day-old rats had higher levels of aspartate (Asp; 24%), glutamate (Glu; 49%) and glycine (Gly; 44%) and lower levels of taurine (Tau; 43%) than 16-day-old rats. In 16-day-old rats, NMDA (30 mg/kg, s.c, 10 min) increased the Glut concentration (48%). This effect was prevented by MK-801 pretreatment (1 mg/kg, s.c, 1 h), which did not modify amino acid concentrations per se. In 30-day-old rats, NMDA treatment increased Glut (24%) and asp (42%) levels/lvIK-801 pretreatment abolished NMDA-induced changes and reduced Tau (26%) and Gly (30%) levels. MK-801 administration alone reduced the concentration of Glut (39%), Asp (54%), Tau (33%) and Gly (31%). It is concluded that both (1) the concentration of Asp, Glu, Gly and Tau and (2) the changes induced by NMDA receptor activation or blockade are different at 16 vs. 30 days of age. The existence of a tonic (positive) control on amino acid levels linked to the NMDA receptor which would be immature or absent at 16 days of age is suggested.

ISSN:0028-3835    

DOI:10.1159/000126460

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effects of sex steroid hormones on the different receptor binding sites of the GABAa molecule remain unclear. In this report we have demonstrated, using autoradiography techniques, that the distribution pattern of the benzodiazepine receptors (a component of the GABAa molecule) in some extrahypothalamic brain regions is altered by both in vivo and in vitro sex steroid hormone treatment. In vivo administration of the sex steroids estradiol and progesterone induced a significant change in [3H]flunitrazepam (benzodiazepine agonist) binding levels in the amygdala, and cortico and posterior brain nuclei of the female rat. In fact, elevated and diminished receptor-binding levels were obtained in the corticomedial amygdala nucleus and in the pontine central gray matter respectively, following the administration of estradiol. Significant hormonal effects were also shown for animals that received only a progesterone dose, as demonstrated by the increased and decreased receptor levels in the basolateral amygdala nucleus and cortex lamina VI and in the substantia nigra pars reticulata, respectively. It was interesting, at this point, to investigate whether the hormone effects on [3H]flunitrazepam binding changes might be mediated through a GABA-dependent activity, because the benzodiazepine and GABAa receptors are coupled to a chloride ion channel in an allosteric manner. When 50 µM GABA was added to the incubation medium, substantially altered binding levels were recorded in animals that received progesterone replacement therapy only. The GABA-induced progesterone effects both increased substantially the binding levels in the oriens-pyramidalis CA1 layer of the hippocampus and in the intermediate gray layer of the superior colliculus as well as reducing receptor levels in the substantia nigra pars reticulata. Due to the significant progesterone effects on [3H]flunitrazepam binding, we also examined whether progesterone per se or whether the potent progesterone metabolite 3α-hydroxy-5α-dihydroprogesterone was responsible for the receptor-binding changes. Addition of this progesterone metabolite not only produced greater binding changes in brain areas that responded to the in vivo progesterone treatment but also increased, in a GABA-dependent manner, [3H]flunitrazeρam binding levels in the lateral amygdala nucleus. These results suggest that the anxiolytic, sedative and anti-aggressive behavioral effects, which are progesterone-dependent, are very likely mediated via a steroid-GABAergic interact

ISSN:0028-3835    

DOI:10.1159/000126461

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The inhibitory effect of female sex steroid hormones on the binding of [35S]t-butylbicyclophosphorothionate [35S]TBPS to the chloride ion channel receptor in different forebrain areas of the female rat proved to be of a differential nature. The in vivo administration of estradiol and estradiol + progesterone were responsible for substantially lower chloride ion channel receptor levels in brain areas that contain elevated steroid receptors, such as the medial preoptic area, the corticomedial amygdala nucleus, the vertical limb diagonal band-medial septal nucleus and the cortex lamina V. The administration of progesterone alone reduced receptor levels in the oriens-pyramidalis CA1 layer of the hippocampus, caudate putamen, cortex lamina VI (brain areas that contain little if any steroid receptors) and in the lateral and basolateral amygdala nucleus (brain sites that contain noninducible progesterone receptors). On the basis of the progesterone-inhibitory activity on the chloride ion channel receptors, it was important to investigate whether progesterone per se or whether the potent progesterone metabolites 3α-hydroxy-5α-dihydroprogesterone (3α,5α-THP) and 3β-hydroxy-5β-dihydroprogesterone (3β,5β-THP) were involved in the binding level changes, and to establish the specific brain sites where these steroid effects occur. In fact, in vitro addition of the 5α-reduced progesterone metabolite produced even greater depressive effects on [35S]TBPS binding not only in the same brain areas as the in vivo progesterone replacement therapy but also in some sites that provided significant receptor level changes following the sequential administration of estradiol + progesterone. However, when the 5β-reduced metabolite was tested on the binding of [35S]TBPS to the chloride ion channel receptor, only the basolateral amygdala nucleus, the cortex lamina VI and the dorsolateral septal nucleus exhibited changes. Because the steroid-mediated chloride ion flux is regulated in a GABA-dependent manner, we next checked for the type of GABA effects on the chloride ion channel receptor levels and found that GABA not only intensified the 3α, 5α-THP inhibitory effects but, together with this progesterone metabolite, was also involved in binding changes in the vertical limb diagonal band-medial septal nucleus. It is interesting to note that the GABA effects on 5β-metabolite-induced receptor changes were not of the enhancing type, but tended, rather, to be inhibitory. Moreover, the addition of the GABA antagonist bicuculline to the in vitro hormone treatment in the presence of GABA, caused a notable and specific inhibitory effect only to 3α, 5α-THP-induced chloride ionophore receptor levels, indicating that this metabolite is probably the main modulator involved in the progesterone-dependent GABAergic functions via a specific interaction with the neurosteroid site of the GABA molecule in the vario

ISSN:0028-3835    

DOI:10.1159/000126462

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0028-3835    

DOI:10.1159/000151231

出版商:S. Karger AG    

年代:1993

数据来源: Karger