摘要:

The endogenous opioid system tonically inhibits the LH-releasing apparatus in adult male rats but not in immature animals. To determine the relationship between the onset of this effect and the peripubertal testosterone rise, male rats were examined at 5-day intervals from day 25 through day 65. They were injected subcutaneously with saline, 0.25 or 1.0 mg/kg body weight naloxone and sacrificed 20 min later. Another group of immature males was castrated, implanted with testosterone-filled capsules and tested with naloxone 4 days later. The peripubertal increase in testosterone and the ability of naloxone to increase serum LH concentrations were both first statistically significant on day 45. Testosterone treatment of immature rats did not induce a naloxone effect. The ability of hypothalamic fragments to release LHRH in vitro in response to naloxone also appeared to occur at the same time as the peripubertal testosterone rise. Hypothalamic fragments obtained from immature male rats treated in vivo with testosterone were capable of responding to naloxone with LHRH release in vitro. These data suggest that in the rat the maturation of the endogenous opioid system is a component of male puberty that is induced by the peripubertal testosterone rise.

ISSN:0028-3835    

DOI:10.1159/000126179

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Adrenal corticosteroids bind to hippocampal glucocorticoid (GR) and mineralocorticoid receptors (MR), thereby affecting neurochemical transmission leading to altered mood, behaviour and neuroendocrine control. Serotoninergic (5-HT) and noradrenergic projections innervate the hippocampus, interacting with corticosteroid-sensitive cells. We have previously demonstrated that lesions of 5-HT neurons reduce hippocampal GR and MR mRNA levels and now examine whether acute or chronic treatment with antidepressant drugs, which potentiate endogenous monoamines by inhibiting their reuptake, affect hippocampal GR and MR mRNA expression in vivo. Rats were treated with amitriptyline (20 mg/kg · day–1), desipramine (10 mg/kg · day–1) or citalopram (20 mg/kg · day–1). After 2 or 14 days animals were killed, RNA extracted and GR and MR mRNA expression quantified by slot blot hybridization. Amitriptyline for 2 days led to a significant increase in MR (by 23 ± 6%, compared with saline-treated controls), but not GR, mRNA expression. After 14 days amitriptyline, expression of both MR (87 ± 27% rise) and GR mRNA (56 ± 18% rise) had increased significantly in hippocampus, but not in parietal cortex. Desipramine for 14 days also increased MR (60 ± 9%) and GR (42 ± 9%) mRNA expression, though 14 days of citalopram altered only MR mRNA expression (17 ± 5%). Thus, antidepressant drug administration elevates MR and GR mRNA expression in hippocampus, but not parietal cortex, in a time-de

ISSN:0028-3835    

DOI:10.1159/000126180

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Altered neuroendocrine sensitivity to estrogen is a characteristic of reproductive aging in female rodents, but its molecular basis is not well understood. The objective of this study was to determine whether altered modulation of hypothalamic proopiomelanocortin (POMC) mRNA by estradiol (E2) is a component of reduced neuroendocrine sensitivity to estrogen in the aging mouse. Young (4 month-old), middle-aged (13 month-old), and old (25 month-old) C57BL/6J mice were ovariectomized, implanted 2 weeks later with Silastic capsules containing E2 or cholesterol (CHOL), and sacrificed 3 days later. Hypothalamic POMC mRNA was measured by solution hybridization/RNase protection, using a RNA probe complementary to a fragment of mouse POMC mRNA. In the group with CHOL implants, POMC mRNA was 36% lower in middle-aged and old mice compared to young mice. E2 treatment reduced POMC mRNA levels by 44% in young mice but failed to lower POMC mRNA in middle-aged and old animals. These results confirm earlier evidence of reduced levels of POMC mRNA in hypothalami of aging rodents and indicate that the ability of E2 to reduce hypothalamic POMC mRNA is lost by middle age.

ISSN:0028-3835    

DOI:10.1159/000126181

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Using hypothalamic explants of male rats, we have shown that the N-methyl-D-aspartate (NMDA) receptors involved in a stimulatory control of gonadotropin-releasing hormone (GnRH) secretion were transiently activated at 25 days around the time of onset of puberty. This was evidenced by studying the dose-related inhibition of veratridine-induced GnRH secretion by MK-801, a usedependent antagonist of NMDA receptors. An increase in sensitivity of GnRH secretion to the inhibitory effect of MK-801 was used as a marker of increased activation of NMDA receptors involved in stimulation of GnRH secretion. Here, we report on data obtained in intact and castrated rats at different ages. The aim was to determine whether the absence of gonads would affect the developmental changes in activation of NMDA receptors that we described recently. In pubertal (50-day-old) rats, orchidectomy resulted in an activation of NMDA receptors which was nonsignificant after 4 days but significant after 13 days. In prepubertal rats orchidectomized at 5 or 10 days and studied 10 days later, the NMDA receptors involved in GnRH secretion were also more activated than in intact animals. Using explants of intact and castrated animals, a similar increase in activation of NMDA receptors was observed between 15 and 25 days of age, a period preceding onset of puberty. Subsequently, between 25 and 50 days, a reduction in NMDA receptor activation was seen. This decrease was observed in intact rats showing normal sexual development and in castrated rats as well. We conclude that (1) in prepubertal and pubertal rats, orchidectomy equally activates the NMDA receptors involved in GnRH secretion, and (2) orchidectomy does not prevent the age-related changes in activation of NMDA receptors involved in GnRH secretion.

ISSN:0028-3835    

DOI:10.1159/000126182

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Retinoic acid has recently been shown to increase growth hormone (GH)-gene transcription rate and GH synthesis in vitro. To investigate the role retinoic acid plays in the neuroregulation of GH secretion we have studied GH responses to growth hormone-releasing hormone (GHRH) in retinoic acid-deficient rats. Compared to normally fed male rats, retinoic acid-deficient rats showed a marked impairment in body weight, which was statistically significant after 3 weeks and maximal after 5-6 weeks (p < 0.001). Yet, in vivo GH responses to different doses of GHRH (1, 5 and 25 µg/kg) in pentobarbital-anesthetized rats were similar in both groups. Also, in vitro GH responses to GHRH, forskolin, and KC1 were similar in perfused pituitary cells taken from control and retinoic acid-deficient rats. However, further studies carried out in freely-moving rats showed the typical GH secretory pattern usually found in male rats of the control group, while retinoic acid-deficient rats displayed a highly variable GH secretory pattern with GH peaks of much lower amplitude. Finally, after gel electrophoresis of in vitro 35S-labelled proteins, no differences were observed in the molecular forms of GH. Considering these findings on normal pituitary responsiveness and alterations in GH pulsatility, our data suggest that retinoic acid deficiency leads to an alteration in the neuroregulation of GH secretion at the central level

ISSN:0028-3835    

DOI:10.1159/000126183

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Using an in vitro continuous perifusion system, the effects of interleukin-1 (IL-1) on adrenocorticotropin (ACTH) secretion at the pituitary level were investigated. On one hand, we observed that IL-1β increases ACTH secretion from perifused anterior pituitary cells in a dose-dependent manner, between 1.5 and 6 pM. This stimulatory action of IL-1 on ACTH was significantly attenuated by a short in vitro dexamethasone pretreatment. This fact suggests a regulatory glucocorticoid negative feedback analogous to that observed upon the pituitary action of corticotropin-releasing factor (CRF). We also examined the effect of simultaneous treatment with IL-1 and CRF. The results indicated that the effect of IL-1 resulted additive to the CRF-induced ACTH secretion. It is concluded that the anterior pituitary could be an important site of IL-1 action to activate the hypothalamic-pituitary-adrenocortical axis function, and that this action is under an inhibitory glucocorticoid regulation

ISSN:0028-3835    

DOI:10.1159/000126184

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Arginine vasopressin (AVP) and oxytocin (OT) responses during an insulin (0.15 IU/kg body weight) tolerance test (ITT) were evaluated in normal men while they were infused with normal saline, glucose or fructose. Insulin-induced hypoglycemia produced significant plasma AVP and OT increments in the control test. The infusion of fructose was unable to change the posterior pituitary hormonal responses to hypoglycemia. In contrast, AVP and OT responses during ITT were completely abolished when the concomitant infusion of glucose prevented insulin-induced hypoglycemia. These data exclude a direct role of hyperinsulinemia in the mechanism underlying the AVP and OT responses during ITT. Furthermore, since glucose, but not fructose, crosses the blood-brain barrier (BBB), the posterior pituitary hormone responses to hypoglycemia appear to be generated by stimulations of glucosensitive areas located inside the BBB.

ISSN:0028-3835    

DOI:10.1159/000126185

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The purpose of the present study was to examine whether repetitive intravenous injections of L-glutamic acid (Glu), like those of N-methyl-D, L-aspartic acid (NMA), are able to elicit a sustained train of gonadotropin releasing hormone (GnRH) discharges from the hypothalamus of the prepubertal male monkey. In order to utilize pituitary luteinizing hormone (LH) secretion as a bioassay of hypothalamic GnRH release, the responsiveness of the gonadotroph of the prepubertal animals was enhanced prior to the study with a chronic intermittent intravenous infusion of the synthetic decapeptide (0.1 µg/min for 3 min every h). Sequential intravenous injections of Glu (150 mg/kg BW) were administered at 3-hour intervals for 6 or 24 h. Although the first injection of this acidic amino acid elicited a robust discharge of GnRH, subsequent stimulation with Glu resulted in GnRH discharges with progressively decreasing magnitudes, and by the 9th injection Glu-induced GnRH release was abolished. Peak concentrations of circulating Glu following the 1st and 4th Glu injection were indistinguishable (3,959 ± 437 vs. 4,139 ± 72 nmol/ml, respectively). Interestingly, the failure of repetitive intravenous injections of Glu to sustain pulsatile GnRH release was not associated with a loss of responsiveness to NMA administration, nor was it accompanied by a corresponding decrement in Glu induced growth hormone (GH) discharges. As previously demonstrated, repetitive intravenous administration of NMA (2-5 mg/kg BW) every 3 h for 9 h sustained pulsatile GnRH secretion without decrement. A similar intermittent infusion of kainic acid (KA; 1 mg/kg BW every 3 h for 6 h), however, elicited a GnRH response that mimicked that observed in response to intermittent Glu treatment. These findings are consistent with the notion that Glu administered by intravenous injection fails to reach the central N-methyl-D-aspartic acid (NMDA) receptors that mediate the sustained train of GnRH discharges elicited in response to repetitive intravenous injections of NMA. Instead, circulating Glu appears to activate non-NMDA receptors in the vicinity of the median eminence. Repetitive activation of these non-NMDA receptors, in contrast to that of the NMDA receptor, fails to sustain an intermittent discharge of GnRH. The Glu induced GH release, which occurred without decrement, was therefore presumably mediated by NMDA receptors on GH releasing hormone cells in close proximity to the median eminen

ISSN:0028-3835    

DOI:10.1159/000126186

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotrans-mitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypotha-lamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.

ISSN:0028-3835    

DOI:10.1159/000126187

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Type II corticosteroid receptor-like immunoreactivity (type Il-ir) was localized at the light- and electron-microscopic levels in the rat cerebellar cortex using BUGR2 monoclonal antibody. In intact rats, type II-ir was observed in the nuclei of basket, stellate, Golgi and Purkinje cells. After 1 week of adrenalectomy, type IIir was barely resolvable in basket, stellate, Golgi and most Purkinje cells. Vermal Purkinje cells showed intense nuclear and cytoplasmic type II-ir. After 4 weeks of adrenalectomy, type II-ir was markedly reduced in most vermal Purkinje cells, however a few in lobules 1-3 and 9 and 10 retained diffuse immunoreactivity. Acute treatment with corticosterone restored nuclear type II-ir to basket, stellate, Golgi and Purkinje cells in the cerebellar hemispheres, flocculi and paraflocculi. In the vermis most Purkinje cells showed nuclear type II-ir following corticosterone treatment. Diffuse type II-ir was, however, retained in a few Purkinje cells in vermal lobules 1-3, 9 and 10. The distribution of GABA-like immunoreactivity (GABA-ir) in the cerebellar cortex was not altered by adrenalectomy or acute corticosterone treatment. 30-60% of type II-ir Purkinje cells in intact rats were GABA-ir. In adrenalectomized and corticosterone-treated rats, a similar proportion of type II-ir Purkinje cells were GABA-ir. The differential regulation of neuronal type Il-ir in the cerebellum by corticosterone may account for some of the known effects of glucocorticoids on motor coordination.

ISSN:0028-3835    

DOI:10.1159/000126188

出版商:S. Karger AG    

年代:1992

数据来源: Karger