摘要:

In this study we have applied the technique of hypothalamo-pituitary disconnection (HPD) to the fetal sheep at 108–112 days of gestation. The pituitary is surgically disconnected from the hypothalamus by the removal of the neural component of the median eminence above the level of the portal circulation. This procedure results in the complete disconnection of the pituitary from the hypothalamus. After HPD, the lactotroph response to the dopamine antagonist chlorpromazine was significantly reduced (p < 0.005) indicating the functional isolation of the pituitary gland from the hypothalamus. The increase in plasma prolactin in response to exogenous thyrotrophin-releasing factor was maintained following HPD. HPD resulted in the complete atrophy of the pars nervosa. At 132–135 days of gestation after HPD there was no change in the volume or appearance of the pars distalis; small infarcts were observed in the pars distalis of some HPD fetuses, but these occupied less than 1% of the volume of the anterior lobe of the pituitary. There was a significant increase (p < 0.05) in the volume of the pars intermedia after HPD. Gestation was prolonged for at least 8 days beyond normal term following HPD, indicating that the processes integral to the initiation of parturition at term had been disrupted. We conclude that HPD provides a good in vivo model for the investigation of the activity of the isolated pituitary gland, and for the examination of the role of neuroendocrine mechanisms in fetal sheep development in the latter third of gestat

ISSN:0028-3835    

DOI:10.1159/000125308

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Glandular kallikrein (a trypsin-like serine protease) is an estrogen-induced and dopamine-repressed protein in the rat anterior pituitary which predominantly exists as a latent zymogen (prokallikrein). Its regulation, presence in estrogen-induced pituitary tumors in F344 rats, and expression in GH3 cells has suggested a localization in lactotrophs (prolactin-producing cells). This study examined the cellular origin of glandular kallikrein using immunocytochemical techniques. Anterior pituitaries from estrogen-treated rats were fixed and embedded in paraffin (for preparation of semi thick sections; 5 µm) or methacrylate (for preparation of thin sections; 1 µm). Glandular kallikrein immunostaining was readily detected in the perinuclear (Golgi) region of parenchymal cells of the anterior pituitary in both thin and semi thick sections. Two-color double immunoperoxidase staining of thin and semi thick sections indicated that glandular kallikrein was localized in cells containing prolactin (PRL) but not other pituitary hormones. Immunoperoxidase staining of consecutive serial thin sections with alternating antisera confirmed a localization of glandular kallikrein in lactotrophs. The results establish that glandular kallikrein is colocalized with PRL in lactotrophs of the rat anterior pituitary. This is consistent with the hypothesis that the function of anterior pituitary glandular kallikrein is linked to PRL in some fashion – possibly as a PRL-processing prote

ISSN:0028-3835    

DOI:10.1159/000125309

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Although a common drug of abuse, cocaine’s effects on cyclic reproductive functions and the neuroendocrine systems regulating these functions have not been studied. Here, we report the effects of cocaine on (1) estrous cyclicity and ovulation rates and (2) the stimulated in vitro release of hypothalamic GnRH and aminergic neurotransmitters directly involved in regulating or modulating GnRH release. Within 7 days of treatment with 10 mg kg–1 day–1 of cocaine HC1 subcutaneously, rats demonstrated significant estrous cycle irregularity including repetitive days of estrus and prolonged periods of diestrus. After 6 weeks of treatment, cocaine-treated rats exhibited a 44.3% decrease in ovulation rates. For the in vitro studies, bilaterally ovariectomized rats were injected with cocaine (10 mg kg–1 day–1) or with saline for 2 weeks. Each rat received estradiol benzoate (50 mg kg–1 day–1 s.c.) for 2 days before sacrifice. Hypothalamic slices were prepared, placed in 0.1 ml microchambers and perfused with modified Krebs buffer (pH 7.4) using a programmable perfusion system. Basal release of norepinephrine (NE) and serotonin (5HT) was significantly increased in the cocaine-treated group versus controls. Ten-minute pulses of 10–7M progesterone (P4) increase NE and 5HT, but not dopamine (DA), release in the saline-treated group. In contrast, pulses of P4 increased NE, but not 5HT or DA, in the cocaine-treated rats. Ten-minute pulses of 0.1 µM NE increased GnRH release in both saline- and cocaine-treated rats. However, the response to pulsed NE was significantly attenuated in the cocaine-treated group. The results of this study demonstrate that cocaine disrupts estrous cyclicity by altering the hypothalamic amine activity necessary for pulsatile hypothalamic GnRH release. However, a direct effect of cocaine on the pituitary gland or ovaries cannot be excluded on the basis

ISSN:0028-3835    

DOI:10.1159/000125310

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The regional distribution of neuropeptide Y-like immunoreactivity (NPY-IR) in the human hypothalamus has been determined using a highly specific immunoradiometric assay. Hypothalami were removed during postmortem examination from 19 subjects. The pituitary stalk and 11 anatomically defined nuclei and areas were microdissected from one or both sides of each hypothalamus. NPY-IR was detectable in the acid extracts of tissue samples prepared from all the hypothalamic regions studied, with the highest concentrations being found in the infundibular nucleus (325 ± 53 fmol/mg wet weight of tissue) and the ventromedial nucleus (217 ± 22 fmol/mg). For the 11 subjects where both sides of the hypothalamus were dissected, values obtained for the areas in one half showed a good degree of symmetry with the corresponding areas on the contralateral side. The infundibular nucleus exhibited the greatest range of values (72–1,137 fmol/mg). Interestingly, variations in other parts of the hypothalamus were observed to parallel those of this nucleus. Expressed as correlation coefficients (r), levels in the infundibular nucleus appeared to be most closely related to those of the ventromedial nucleus (VM; r = 0.89) and paraventricular nucleus (PV; r = 0.84). In addition, retrospective analysis of the clinical histories showed that all patients with very high NPY levels in the infundibular nucleus (621.0 ± 107.7 fmol/mg; n = 8) had suffered from respiratory failure or severe dyspnea of at least 10 days duration prior to death. The remaining patients (166.7 ± 17.1 fmol/mg; n = 11) had either died 48 h from the onset of cardiorespiratory difficulties or of unrelated causes. In the patients with raised concentrations in the infundibular nucleus, correspondingly high levels of NPY were also observed in the PV and VM nuclei, suggesting that functional changes in these NPY pathways may be the result of prolonged respiratory dis

ISSN:0028-3835    

DOI:10.1159/000125311

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

To determine whether the prolactin (PRL) circadian rhythm, with its characteristic nocturnal rise, persists during the hyperprolactinemia of lactation, PRL levels were analyzed in blood samples collected hourly for 24 h from 20 mothers, 4–46 months postpartum. The circadian rhythm of PRL persisted throughout lactation as manifested by: (1) significantly higher mean nighttime than daytime PRL levels in the whole sample, despite higher daytime nursing durations; (2) the distribution of zenith levels which most frequently occur between 23.00 and 07.00 h, when nursing duration is lowest, and which are almost absent between 07.00 and 23.00 h, when nursing duration is highest, and of nadir levels, which have an opposite pattern; (3) spontaneous PRL surges that are more frequent, longer, and of higher magnitude at night than during the day, and (4) the larger magnitude of suckling-induced PRL release from late afternoon through the night compared to the morning in some women. Our data suggest that the mechanisms responsible for the circadian rhythm in PRL secretion are relatively independent of the mechanisms of suckling-induced release. We propose that the nocturnal rise in PRL during lactation functions to ensure a robust milk supply during an extensive nonsuckling interva

ISSN:0028-3835    

DOI:10.1159/000125312

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effect of perinatal hypothyroidism on the number and distribution of hippocampal kainic acid binding sites was examined in rats. Timed pregnant Sprague-Dawley rat dams were given water containing either 0.02% propylthiouracil (PTU) or untreated water from gestational day 18 until their litters were weaned at postnatal day 31. The offspring were sacrificed at 31 or 120 days of age, blood samples collected and their brains frozen. In the 31-day-old rats, serum thyroxine, serum triiodothyronine, total body weight and whole brain weight all indicated that the PTU-treated rats were hypothyroid. Hippocampal kainic acid binding was analyzed in sections of dorsal and ventral hippocampal formation by in vitro 3H-vinylidene kainic acid (VKA) autoradiography. Compared to the untreated controls, specific 3H-VKA binding was reduced by 43% in the ventral hippocampal formation stratum lucidum of 31-day-old FΓU-treated rats. Specific 3H-VKA binding was not different in the dorsal hippocampal formation. Saturation of 3H-VKA binding studies indicated that the decrease – induced by PTU treatment – in ventral hippocampal 3H-VKA binding was due to a reduction in the total number of 3H-VKA binding sites. At 120 days of age, 3 months after the cessation of the PTU treatment, serum thyroid hormone levels were not different than those of controls, indicating a recovery of thyroid hormone function after the perinatal PTU treatment. However, specific 3H-VKA binding remained significantly reduced in the ventral hippocampal formation of 120-day-old rats. This observation indicated that the decrease in 3H-VKA binding at 31 days of age was not simply due to a delay in the development of this system and that perinatal hypothyroidism can cause long-lasting alterations in the total number of hippocampal kainic acid binding s

ISSN:0028-3835    

DOI:10.1159/000125313

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effects of central 5-hydroxytryptamine (5-HT) infusions on the cold-stimulated thyrotropin (TSH) levels were studied in male rats. Stainless-steel cannulas were implanted stereotaxically into the anterior or the posterior third ventricle or just lateral to the hypothalamic paraventricular nuclei bilaterally 7 days before experiments. Infusion of 5-HT(4.5 and 9 µg/rat) into the posterior third ventricle attenuated significantly the cold-stimulated TSH levels. Inversely, infusion of 5-HT (9 µg/rat) into the anterior third ventricle augmented significantly the TSH cold response. Bilateral 5-HT infusions into the vicinity of the hypothalamic paraventricular nuclei did not affect the TSH cold response. Serum prolactin levels increased significantly after 5-HTadministration into the anterior and the posterior third ventricle, but no consistent effect on growth hormone (GH) levels could be detected. Infusion of 5-HT into the anterior and the posterior third ventricle decreased body temperature irrespective of the observed hormonal response to 5-HT. The results are in favor of a dual and possibly site-dependent role for 5-HTin the regulation of the cold-stimulated TSH secretion in the rat. The opposite effects of 5-HT on the TSH cold response may result from the predominant inhibition of either the thyrotropin-releasing hormone or the somatostatin-secreting cell group

ISSN:0028-3835    

DOI:10.1159/000125314

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

In humans, corticoids suppress growth and growth hormone (GH) secretion elicited by a variety of stimuli, while in the rat they potentiate both in vivo and in vitro GH release. To further study this problem, growth-hormone-releasing hormone (GHRH) tests were performed in 6 nonobese Cushing’s syndrome patients and 6 controls. The normal GHRH-induced GH secretion was completely abolished in the Cushing’s syndrome group. To study the action of shorter corticoid exposures, 34 volunteers were subjected to four tests each: placebo treatment (control); dexamethasone (Dex) administration 4 mg i.v., 3 h before; Dex 8 mg p.o., 12 h before, and Dex 22 mg p.o. over the 2 days before the pituitary challenge that was always administered at 0 min (12.00 h). In the first test (n = 9), GHRH (1 µg/kg i.v.) induced a GH peak of 14.5 ± 3.8 ng/ml (control) that was potentiated by Dex 4 mg i.v. administered 3 h before (26.4 ± 6.8 ng/ml). On the contrary, longer Dex treatments suppress GHRH-induced GH values (6.0 ± 1.1 ng/ml after Dex 8 mg and 1.8 ± 0.3 ng/ml after Dex 22 mg). Clonidine administration 300 µg p.o. (n = 7) increased GH secretion with an area under the secretory curve (AUC) of 1,274 ± 236 that was potentiated by Dex 4 mg i.v. given 3 h before clonidine (2,380 ± 489) and reduced by Dex 8 mg, the reduction being significant only after 22 mg Dex(595 ± 47). When arginine 30 g was used as pituitary challenge (n = 6), the GH peak (19.1 ± 4.8 ng/ml) and the AUC (1,318 ± 322) were not significanty altered by Dex 4 mg nor by Dex 8 mg, but clearly reduced after pretreatment with Dex 22 mg (11.1 ± 4.6 ng/ml peak; 635 ± 189 AUC). The action of Dex was rather selective for GH secretion, because it did not alter (n = 6) prolactin, luteinizing hormone and follicle-stimulating hormone stimulated by a combined administration of luteinizing-hormone-releasing hormone and thyrotropin-releasing hormone. In this group, thyrotropin was only altered after the higher (22 mg) Dex treatment. These results showed a dual action of Dex on GH release in man. Short-term treatment potentiated basal and GHRH-stimulated GH secretion. The stimulatory action of corticoids becomes an inhibitory one when longer treatments are employed, suggesting, though not proving, to be mediated by somatostatin release from

ISSN:0028-3835    

DOI:10.1159/000125315

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

There is increasing evidence that the neuroendocrine system is responsive to hormonal signals generated by the immune systems. In particular, interleukin-1 and thymosin have been shown to stimulate the pituitary-adrenal axis in young animals. We report here that homeostatic thymus hormone (HTH), a well-characterized thymic preparation, increases plasma levels of corticosterone but not prolactin (PRL) in a dose- and age-dependent manner in male Sprague-Dawley rats. Young (3 months) and old (26 months) conscious, free-moving animals carrying an indwelling atrial cannula received the substances to be tested via the cannulas. Plasma samples were taken every 30 min for 5 h and hormones were measured by radioimmunoassay. HTH doses of 1 and 8 mg/kg body weight injected into young rats elicited a 7.8- and 12.8-fold increase in plasma corticosterone, respectively, as compared to saline-injected controls. The HTH-induced peak corticosterone levels were reached within 1.5 and 2.5 h after HTH injection. Plasma PRL was not affected by HTH in either age group. A single dose of 8 mg HTH/kg body weight induced a smaller corticosterone response in old than in young rats, although the time course of the response was similar in both age groups. The present results further suggest the existence of a lymphoid-neuroendocrine axis in young animals. The data also suggest that a disruption in immune-endocrine integration occurs during aging in rats.

ISSN:0028-3835    

DOI:10.1159/000125316

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

To assess more closely the physiological mechanism(s) by which ethanol (ETOH) delays the onset of female puberty, we have evaluated its effects on body weight, the vaginal opening (VO)-first diestrus (D1) interval and the serum concentrations of growth hormone (GH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) throughout the peripubertal period in the rat. Using a specific intragastric feeding regimen, 29-day-old rats began receiving either a liquid diet containing ETOH or an isocaloric control liquid diet. Additional controls consisted of animals maintained on laboratory chow and water provided ad libitum. Animals were either killed between 32 and 37 days of age, categorized with regard to their phase of puberty and their serum hormones measured; or, in some animals, the ETOH liquid diet was administered through day 41 and at that time replaced by the control liquid diet in order to determine if recovery would occur. Our results indicate that ETOH-treated animals showed significantly lower body weights and a significantly longer mean VO-D1 interval than the control animals. Also, serum GH and LH levels were significantly lower in the ETOH-treated animals; however, FSH levels were not affected. Administration of the ETOH liquid diet through day 41 produced varying detrimental effects on the onset of puberty and subsequent removal of ETOH from the diet resulted in rapid growth of the animals, followed by the onset of puberty. These results demonstrate: (a) that ETOH administration during the peripubertal period delays the onset of female puberty in the rat; (b) that this effect is associated with deficiencies in both GH and LH secretion, and (c) that, although delayed, growth and sexual maturity can occur after removal from the drug from the diet.

ISSN:0028-3835    

DOI:10.1159/000125317

出版商:S. Karger AG    

年代:1990

数据来源: Karger