摘要:

If a primary physiologic action of TRH is to regulate the set-point for negative feedback, a sudden drop in plasma thyroid hormone concentration should stimulate the same rate of in vivo increase in TSH secretion from normal and TRH-deprived thyrotrophs. To test this hypothesis, 3 experiments were performed in which young adult female rats were divided into 3 groups of 6-10 rats each: intact controls, hypothalamic paraventricular nuclei ablation (PVN) and sham-ablated (Sham). Sham and PVN rats were thyroparathyroidectomized 2-4 weeks after brain lesions and serial blood samples taken in all groups at frequent intervals from 0 to 58 days post-thyroidectomy. Plasma TSH was significantly higher than in intact controls by 3 days post-thyroidectomy in both the Sham and PVN groups (p < 0.05). At 14 days PVN plasma TSH was 4 × higher and at 30 days 8 × higher than in intact controls and remained consistently at 50% of that of the Sham group. There was no statistical difference between PVN and Sham in the rate of increase in TSH. Plasma T4 was 40% lower in PVN than in Sham at the time of thyroidectomy and became undetectable in both by day 3. The prompt parallel rate of rise of plasma TSH in Sham and PVN groups following thyroidectomy indicates that a primary physiologic action of TRH in the thyrotroph is to control the set-point for thyroid hormone negative feedback on TSH secretion. However, this does not appear to be the sole mechanism by which TRH influences TSH secretion since even by 2 months post-thyroidectomy, when plasma TSH concentration had plateaued, plasma TSH was 50% lower in PVN than in Sham rat

ISSN:0028-3835    

DOI:10.1159/000126408

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We have used in situ hybridization histochemistry to determine the effect of hippocampal-hypothalamic disconnection on hypothalamic thyrotrophin-releasing hormone (TRH) and anterior pituitary thyrotrophin β subunit (TSHβ) transcripts in adult male CFY rats. Electrothermal lesions of the fornix pathway significantly increased TRH and TSH transcripts and increased circulating levels of triiodothyronine (T3). Fornix transection did not, however, prevent feedback regulation of TRH and TSH transcripts during exogenous T3-induced hyperthyroidism or propylthiouracil-induced hypothyroidism. Hippocampal inputs to the hypothalamus contribute to setting the basal activity of the thyroid axis, but do not mediate the feedback effects of T3

ISSN:0028-3835    

DOI:10.1159/000126409

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The neurotransmitter neuropeptide Y (NPY) is abundant in the hypothalamus where its actions include the potent stimulation of food intake. The peripheral metabolic and hormonal signals involved in its regulation are not clear. The aim of this study was to investigate possible actions of corticosteroids and insulin on hypothalamic NPY synthesis and content in vivo. We measured NPY content in individual hypothalamic nuclei, and hypothalamic NPY mRNA by Northern blotting in whole hypothalamus in rats treated with dexamethasone (0.4 mg/kg/day) and dexamethasone plus insulin (60 U/kg/day), compared to controls. The effect of stopping dexamethasone treatment was also studied. Dexamethasone treatment produced significant increases in NPY in the paraventricular (11.0 ± 1.3 vs. 7.1 ± 0.4 fmol/µg protein, p < 0.05) and arcuate (6.2 ± 0.3 vs. 3.8 ± 0.2 fmol/µg protein, p < 0.001)nuclei of the hypothalamus, paralleled by a 38% increase in total hypothalamic NPY mRNA (p < 0.05). These changes were not seen in the group treated with dexamethasone plus insulin. In the group in whom dexamethasone was stopped, NPY mRNA was unchanged compared to controls, but peptide content remained increased in the arcuate but not the paraventricular nucleus (arcuate 7.7 ± 0.7 vs. 5.5 ± 0.7, PVN 4.9 ± 1.0 vs. 4.7 ± 0.9 fmol/µg protein). Thus hypothalamic NPY and its mRNA were increased by cortico-steroid administration, and this effect was prevented by systemic insulin treatment. This dual regulatory system for hypothalamic NPY may be important in the control of food intake by corticosteroids a

ISSN:0028-3835    

DOI:10.1159/000126410

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The activity of the GnRH pulse generator in the rhesus monkey is associated with abrupt increases in multiunit electrical activity (MUA) volleys recorded from the mediobasal hypothalamus that precede each pulse of LH in the peripheral circulation. In long-term ovariectomized animals the duration of these MUA volleys is 10–25 min and consists of a brief initial ‘overshoot’ followed by a plateau phase that ends in a rapid decline to baseline activity. In intact monkeys, however, the MUA volley lasts only 1–3 min, a duration equivalent to the overshoot in ovariectomized animals. In addition, the maximal frequency of neuronal activity during each MUA volley is reduced in normal animals when compared to castrates. As shown in earlier studies, estradiol given to ovariectomized monkeys causes a reduction in the duration of MUA volleys to that characteristic of intact animals within 3–5 h. In contrast to this acute effect of estradiol, the increase in MUA volley duration following ovariectomy is a gradual phenomenon, 4–6 weeks being required to achieve the MUA volley duration observed in long-term ovariectomized monkeys. A similar slow time course was observed for the increase in maximal neuronal frequency during each MUA volley. This protracted effect of ovariectomy on MUA volley duration and firing rate may be the consequence of hypothalamic remodelling but this consideration must be tempered by the observation that estradiol reverses these phenomena w

ISSN:0028-3835    

DOI:10.1159/000126411

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

It is almost generally accepted that an acute-phase ACTH response induced by interleukin (IL)-1 is mediated principally by CRH release from the hypothalamus. However, the precise cellular site of action of IL-1 in activating the CRH neuronal system remains to be determined. Two likely candidates comprise the paraventricular nucleus (PVN) where CRH neuronal cell bodies are located, and the median eminence (ME) where their nerve endings are terminated. Therefore, in this study we performed a comparative perfusion of the ME and the PVN with increasing concentrations of recombinant human IL-1β utilizing the push-pull perfusion technique in freely moving rats. We measured the plasma ACTH and ME and PVN levels of CRH, and also of AVP, because AVP, another secretagogue of ACTH, has its cell body in the PVN and axon terminals partly in the ME. In control groups, the ME or the PVN was perfused with artificial cerebrospinal fluid between 12:00 and 15:00 h, and perfusates and blood samples were collected every 20 min. In the other groups, either the ME or the PVN was perfused with three increasing concentrations (0.1, 1.0, and 10 nM) of recombinant human IL-1β dissolved in artificial cerebrospinal fluid only between 13:00 and 14:00 h with all the other procedures run in the same way as in the controls. In the control perfusions, the hypothalamic release of CRH and AVP and the plasma ACTH did not change significantly during the entire period of observation. In the ME perfusion with IL-1β, 1.0 and 10 nM, but not 0.1 nM, of the cytokine significantly and dose-dependently stimulated CRH and AVP secretions in the ME and the plasma ACTH. ACTH responses during the PVN perfusion with IL-1β were similar to those during the ME perfusion, except that at the PVN the lowest concentration (0.1 nM) of the cytokine was already effective in stimulating ACTH secretion. These in vivo data suggest that IL-1β may act on both the ME and the PVN to stimulate CRH and,’ thereby, ACTH secretions. The secretory response of hypothalamic AVP to IL-1β, which was similar to that of CRH, suggests that not only CRH but also AVP may mediate the IL-1β stimulation of ACTH s

ISSN:0028-3835    

DOI:10.1159/000126412

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Severe exercise in young females is a potent cause of menstrual irregularity, although the exact pathogenesis is currently unknown. We performed a cross-sectional endocrine and metabolic analysis of a group of elite athletes and dancers in order to establish which variable, if any, was specifically associated with changes in menstruation. By using a step-wise discriminant analysis, two independent predictors, elevated serum cortisol and insulin-like growth factor binding protein 1 (IGFBP-1) levels, were found to account for the majority (67%) of the variance. IGFBP-1 is a hepatic protein which is acutely and inversely regulated by insulin, and is thought to modulate the peripheral actions of IGF-1. While the change in serum cortisol may reflect activation of central stress pathways, these findings suggest for the first time that there is a second peripheral signal, IGFBP-1, which may relate the availability of metabolic fuels to the control of reproduction.

ISSN:0028-3835    

DOI:10.1159/000126413

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The role of GABA neurons in the control of pulsatile release of LHRH was investigated by checking the effect of the GABAa receptor agonist, muscimol, and antagonist, bicuculline, on the electrical activity of the luteinizing hormone-releasing hormone (LHRH) pulse generator in the ovariectomized rat fitted with chronically implanted electrode arrays in the medial basal hypothalamus. In untreated control animals, the hypothalamic multiunit activity (MUA) exhibited, at an average of 20.5-min intervals, characteristic increases (volleys), each of which was associated with the initiation of an LH pulse. A bolus i.v. injection of muscimol (2 mg/kg) significantly increased the interval between MUA volleys and LH pulses without affecting the pulse amplitude. Continuous i.v. infusion of saline increased the interval between MUA volleys to an average of 24.1 min without affecting the LH pulse amplitudes. Bicuculline infusion (10 mg/kg/h) altered neither the interval between MUA volleys nor the pulsatile release of LH. This was further checked in the condition where presynaptic inhibition by opioid peptides on the noradrenergic system was presumably decreased by naloxone. Naloxone infusion (0.5 or 0.7 mg/ kg/h) caused the MUA volleys to occur markedly frequently, an average of 13.8-min intervals. The interval during combined infusion of bicuculline with naloxone was an average of 16.2 min, suggesting that bicuculline could not decrease the interval that was set by naloxone. The results show that, although exogenous GABAa receptor agonist is capable of inhibiting the activity of LHRH pulse generator, the reduction in the endogenous GABAa receptor activity does not cause a significant effect, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. Further, together with the well-known fact that activation of GABAa receptor hyperpolarizes neurons postsynaptically, it is assumed that the GABAergic system, unlike the opioidergic one, is not involved in the presynaptic inhibition of the adrenergic receptor system which is probably implicated in the frequency control of LHRH pulse generator.

ISSN:0028-3835    

DOI:10.1159/000126414

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

LH secretion is under hypothalamic control, mostly through GnRH. Hypothalamic extracts stimulate LH release in vitro, an action usually attributed to the presence of GnRH. However, the presence of other LH-releasing factors cannot be ruled out since there are other neuromediators endowed with the capacity to influence LH release. We analyzed the presence of an LH-releasing activity in bovine median eminence extracts (ME extracts) different from GnRH using cultured rat pituitary cells. Both, GnRH and ME extracts caused a dose-dependent stimulation of LH release. The maximum response obtained with ME extracts (up to 10-fold the respective baseline) was significantly greater than the maximum response obtained with GnRH (up to 5-fold the respective baseline). Monoclonal or polyclonal GnRH antibodies in the solid phase completely eliminated the LH-releasing activity of 10–7 MGnRH; in contrast, they only partially removed the activity present in ME extracts. The GnRH receptor blocker, Nal-Glu, 10–7M, which completely blocked the effect of GnRH could not totally suppress the LH-releasing activity of ME extracts. These findings indicate that ME extracts contain, in addition to GnRH, an LH-releasing activity not attributable to GnRH because it differs in its immunoreactivity and in its ability to stimulate LH release when GnRH receptors are bloc

ISSN:0028-3835    

DOI:10.1159/000126415

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The rat arginine vasopressin (AVP) genomic sequence has been utilized to develop a line of transgenic mice homozygous and heterozygous for the transgene. Expression of the rat AVP gene was demonstrated by Southern blotting and resulted in increased amounts of AVP in hypothalamus and frontotemporal brain cortex. Secretion of AVP from the neurohypophysial system results in an increased concentration of the hormone in the plasma and in an increased excretion in the urine in amounts three to five times those of normal mice. Extraneural ectopic hormone production was found only in the pancreas. Despite chronic hypersecretion of AVP, 24-hour urine volume and osmolality did not show evidence of increased antidiuretic hormone action on the kidney, so that, under basal conditions, the water balance in the animals is unaffected.

ISSN:0028-3835    

DOI:10.1159/000126416

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The release of norepinephrine (NE) and its metabolites in the central nucleus of the amygdala was measured using in vivo microdialysis during immobilization (IMMO) stress in conscious rats. Animals underwent 2-hour periods of IMMO either once or daily for 7 days. Extracellular fluid concentrations of NE, dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were measured before, during, and after IMMO. Microdialysate levels of NE and DHPG attained 2- to 3-fold increments during the 1 h of IMMO and declined thereafter, whereas MHPG and DOPAC levels attained maximal levels of about twice basal concentrations during the 2- or 3-h after initiation of IMMO. After the sixth IMMO basal levels of NE, DHPG, MHPG, and DOPAC were decreased, and NE, DHPG, and DOPAC responses during the seventh IMMO failed to attain levels found during the first IMMO, although the absolute changes during IMMO were similar between animals subjected to IMMO once or seven times. The results indicate that acute IMMO increases synthesis, release, and metabolism of NE in the central nucleus of the amygdala and that repetition of IMMO decreases basal catecholamine synthesis and noradrenergic turnover in this brain region, without inhibiting acute noradrenergic responses.

ISSN:0028-3835    

DOI:10.1159/000126417

出版商:S. Karger AG    

年代:1993

数据来源: Karger