摘要:

AbstractAlthough until relatively recently assumed to be devoid of innervation, there is now ample proof that the adrenal cortex receives specific neurones of several types. A general interpretation of their roles in the regulation of adrenocortical function has not been forthcoming, probably because of the variety of the different experimental approaches which have been used, and the heterogeneous observations which have been made. We here summarize the evidence which is available, and offer the view that neural inputs may provide fine tuning of the responses to systemic factors such as ACTH, through direct actions on specific adrenocortical cells. However, neural regulation also provides an integrative function, through actions on the flow of blood through the gland, which itself exerts a powerful influence on adrenocortical function.

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00578.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractPrairie voles (Microtus ochrogaster) are monogamous mammals that form male‐female pair bonds. Partner preference formation, one component of the pair bond in prairie voles, occurs following male‐female cohabitation and is facilitated by mating. The peptide hormone oxytocin is released during physical contact and particularly following vaginal stimulation. Oxytocin has been implicated in mother‐infant bond formation. The present study tested the hypothesis that oxytocin participates in the partner preference component of pair bond formation in adult prairie voles. Ovariectomized female prairie voles were implanted with osmotic mini‐pumps releasing oxytocin (1–100 ng/h) or artificial cerebrospinal fluid (CSF). Pumps were implanted intracerebroventricularly or subcutaneously and females then were housed for 6 h with a male partner, followed by a preference test in which females could elect to spend time with either the partner or an unfamiliar male. Females in groups that received centrally‐administered oxytocin (10 or 100 ng/h), but not CSF, exhibited a significant preference for the partner present during infusion. The induction of a partner preference after oxytocin administration appeared specific for central oxytocin pathways as peripheral oxytocin administration was ineffective. Moreover, central administration of a selective oxytocin receptor antagonist inhibited the behavioral effect of exogenous oxytocin. These results suggest that oxytocin may be one factor contributing to the development of partner preferences in this monoga

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00579.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractLong term changes in the secretion of prolactin were monitored in groups of hypothalamo‐pituitary disconnected rams (HPD rams, n = 8) and control rams (HPD sham‐operated and unoperated, n = 8) while exposed to an artificial lighting regimen of alternating 16‐weekly periods of long days (16L : 8D) and short days (8L : 16D) for 72 weeks, and during a treatment with subcutaneous constant‐release implants of melatonin under long days. The HPD rams showed all the clinical characteristics of complete pituitary disconnection (diabetes insipidus, gonadal regression and slight obesity), and were unresponsive to a range of provocation tests (exposure to a barking sheep dog, cannulation of the jugular vein, injection of serotonin and NMDA) which caused acute changes in the blood plasma concentrations of prolactin in the controls. Nevertheless, there was a clearly defined cycle in the blood concentrations of prolactin in the HPD rams related to the imposed lighting regimen with values 10‐fold higher under long days compared to short days (HPD mean ± SEM: 90.1 ± 24.7vs9.4 ± 2.0 μl, long vs short day respectively, P<0.001). The temporal pattern was very similar to that observed in the controls, although the concentrations of prolactin were higher in the HPD rams and more variable (control mean ± SEM: 55.6 ± 3.6 vs 3.0±0.5 μl, long vs short day, P<0.001). There was a corresponding cycle in the growth and moulting of the wool in the HPD rams consistent with a biological response to the photoperiodically‐induced changes in the secretion of prolactin. The diurnal rhythm in the blood concentrations of prolactin was absent in the HPD rams, but there was a normal rhythm in the secretion of melatonin. The treatment of the animals with constant‐release implants of melatonin under long days caused a marked decrease in the blood concentrations of prolactin in both the HPD and control rams. The overall conclusion is that the endogenously generated daily melatonin signal which encodes daylength acts directly in the pituitary gland to mediate the effects of photo‐period on the secretion of prolactin. The photo‐period transduction pathway thus b

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00580.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractTo study mechanisms underlying the modulation of luteinizing hormone‐releasing hormone receptor (LHRH‐R) during lactation and the estrous cycle, we used a reverse transcriptase‐polymerase chain reaction (RT‐PCR) procedure to generate a probe for rat LHRH‐R messenger RNA (mRNA). Using primers based on the mouse sequence, we amplified an approximately 300 bp fragment from rat pituitary complementary DNA. This PCR product was shown to be part of LHRH‐R cDNA by direct sequencing and by comparing to the rat LHRH‐R cDNA reported recently. Then, this PCR fragment was used as a probe for northern blotting analysis.The level of LHRH‐R mRNA in the pituitary was significantly decreased during lactation, by approximately 80%, compared to that of ovariectomized and intact (diestrous and metestrous cycling) rats while no statistical difference in glyceraldehyde‐3‐phosphate‐dehydrogenase (GAPDH) mRNA level was observed between groups. During the estrous cycle, the level of LHRH‐R mRNA in the pituitary was about two‐fold higher on diestrous day 2 and the morning of proestrus than that on diestrous day 1 and quickly returned toward control level by noon of proestrus. In addition, we found that GAPDH mRNA levels from a so‐called housekeeping gene often thought to be unchanged under different conditions, were significantly higher on proestrus while levels of 18S rRNA were not significantly changed.The large decrease in LHRH‐R mRNA during lactation could account for the changes in LHR

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00581.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIn the pregnant rat the osmotic drive to oxytocin neurones is reduced and oxytocin secretion itself is inhibited by endogenous opioids. Coupling of the anterior peri‐third ventricular input pathway, involved in osmoregulation, to magnocellular oxytocin neurones was studied in urethane‐anaesthetized virgin and 21 day pregnant rats using electrical stimulation of the region anterior and ventral to the third cerebral ventricle (AV3V region) to drive the oxytocin neurones, and giving naloxone to prevent the action of any endogenous opioids on the system. Trains ofstimuli (0.5 mA, 1 ms pulses, 10 s on 10 s off, at either 10 Hz or 25 Hz for 10 or 2 min respectively) were given at 20 or 30 min intervals via an electrode stereotaxically‐implanted in the AV3V region, and femoral arterial blood plasma samples collected immediately before and after each stimulation were radioimmunoassayed for oxytocin concentration. The first (control) AV3V stimulation increased plasma oxytocin concentration reproducibly and similarly in virgin and 21‐day pregnant rats. Naloxone administered 10 min before the second stimulus increased basal plasma oxytocin concentration in virgin and pregnant rats and increased the oxytocin secretory response to 25 Hz AV3V stimulation in virgin but not pregnant rats, and the response was significantly greater in virgin rats. Naloxone reveals oxytocin secretion unrestrained by endogenous opioids, therefore it appears that there is an opioid‐independent reduction in the excitatory coupling of the AV3V input to oxytocin neurones which may explain the reduced osmoresponsiveness of oxytocin neurones at the end of pregnancy. In other experiments, morphine (μ‐opioid agonist; at 1&5 mg/kg 5 min before the second and third stimulation periods respectively) or U50,488 (κ‐opioid agonist; 0.5 and 2.5 mg/kg respectively) was given to test the opioid sensitivity of the oxytocin neurone response to stimulation of the AV3V input. Morphine did not significantly affect the oxytocin secretory response to 25 Hz AV3V stimulation in either virgin or pregnant rats but there was a significant dose related inhibition of the oxytocin secretory response to 10 Hz stimulation in both groups. U50,488 also inhibited the oxytocin secretory response to 25 Hz AV3V stimulation in a dose‐related manner in both virgin and pregnant rats. The inhibitory effects of morphine and U50,488 were not different between virgin and pregnant rats; this indicates that central opioid interactions with the AV3V input to oxytocin neurones are not changed in pregnancy. The initial similar oxytocin secretory response to AV3V stimulation in pregnant and virgin rats seems to be a product of a reduced effectiveness of the excitatory AV3V input to oxytocin neurones in late pregnancy and the previously established reduced posterior pituitary sensitivity to inhibitory e

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00582.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe excitatory amino acid glutamate and especially its NMDA subtype receptor are important components of the neural system that regulates sexual maturation. It is known that multiple daily injections of immature rats and monkeys with NMDA will induce precocious puberty. We have previously reported that a single daily injection of NMDA administered from 27 days of age to the day of vaginal opening (VO) is sufficient to synchronize and slightly accelerate (1–2 days) first ovulation in female rats. We have now optimized this treatment schedule and show that a higher dose of NMDA (20 mg/kg), or the racemic mixture N‐methyl‐D,L‐aspartate (NMA; 30 mg/kg), initiated earlier in development (24 days to VO) significantly advances first ovulation (4 days). Rats induced to ovulate prematurely had normal estrous cycles. We also report that the same degree of precocity can be obtained when injections are discontinued well before first ovulation occurs. For example, NMA administered from day 21 to 25 or from day 24 to 28 accelerates sexual maturation to the same degree as if injections were continued until VO was observed. It is clear that the hypothalamic‐pituitary‐ovarian (H‐P‐0) axis is stimulated by daily NMDA treatment as shown by the dose‐related luteinizing hormone (LH) release and by an estrogen‐dependent rise in uterine weight. However, stimulation of the P‐O axis with daily injections of GnRH (5 ng/100 g), which elicits an LH response slightly greater than NMDA (20 mg/kg), does not advance puberty. This suggests that NMDA induces some change in hypothalamic control which is not directly related to LH secretion. Interestingly, there also seems to be a critical period of NMDA effectiveness because daily injections of NMA (30 mg/kg) from day 16 to 20 do not induce precocious puberty. Since the ovaries respond with increased estrogen production (increased uterine weight) to gonadotrophin stimulation at this early age (16 days) we conclude that the hypothalamus may be relatively unresponsive to stimulation with NMDA.Paradoxically the hypothalamus is also hyporesponsive to NMDA in the period preceding spontaneous first ovulation. We now show that an LH dose‐response curve for NMDA at age 28 days demonstrates that in NMDA‐treated rats the LH response to NMDA is less than in the control group. Further, the hyporesponsiveness is not due to pituitary desensitization since an LH dose‐response curve for GnRH at age 28 days is identical in the NMDA‐treated and control groups.In conclusion we have determined that precocious ovulation can be induced by single, daily injections of NMDA beginning no earlier than postnatal day 21. In the peripubertal period the LH response to NMDA is severely attenuated in both treated and control rats. The evidence therefore suggests that contrary to the prevailing view, the H‐P‐O axis becomes less sensitive with the approach of puberty even though NM

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00583.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractChronic glucocorticoid excess or deficiency is associated with hippocampal dysfunction and neuronal death. 11β‐hydroxysteroid dehydro‐genase (11β‐OHSD), which catalyses the reversible conversion of corticosterone to inactive 11 ‐dehydrocorticosterone, regulates glucocorticoid access to receptors in the kidney and liverin vivo. The enzyme is also present in the hippocampus where it might modulate glucocorticoid action. We examined the effects of corticosteroid manipulations on hippocampal and peripheral 11β‐OHSD. In the hippocampus, chronic adrenalectomy (10 days) had no effect on 11β‐OHSD activity, compared to sham‐operated controls. Treatment of adrenalectomized animals with dexamethasone (200 μg/kg.day−1), but not aldosterone (20 μg/kg.day−1), for 10 days significantly increased hippocampal 11β‐OHSD activity compared with sham or adrenalectomized rats (22% and 23% rise respectively, P<0.05). These effects reflect changes in transcription of the liver‐type 11β‐OHSD gene, with dexamethasone significantly increasing 11β‐OHSD mRNA expression in the hippocampus compared with sham or adrenalectomized animals (32% and 70% higher respectively, P<0.05). In the liver, adrenalectomy significantly reduced 11β‐OHSD activity (16% lower), which was restored to sham levels by dexamethasone, but not aldosterone. Similar trends were seen in 11β‐OHSD mRNA expression, although these did not reach significance. None of the manipulations altered 11β‐OHSD activity or mRNA expression in the kidney. The hippocampal effects of dexamethasone were similar to those of chronic stress (arthritis) which increased 11β‐OHSD activity (20% rise, P<0.05), although this was not reflected at the level of mRNA. Thus, hippocampal (and hepatic, but not renal) 11β‐OHSD appears to be regulated by chronic glucocorticoid manipulations and stress. Hippocampal 11β‐OHSD may thus ensure optimal long‐term corti

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00584.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractChronic hyponatremia is known to cause inhibition of pituitary vasopressin (AVP) and oxytocin (OT) secretion in response to most physiological stimuli, as well as a marked inhibition of synthesis of these peptides. Because many studies have implicated neurohypophyseal peptides in the regulation of pituitary prolactin (PRL) secretion, we investigated the effects of chronic hyponatremia on basal and stimulus‐induced PRL secretion in rats. Hyponatremia was induced by subcutaneous infusion of 1‐deamino‐[8‐D‐arginine]‐vasopressin (dDAVP) (5ng/h) to rats fed a nutritionally balanced liquid diet, and plasma [Na+]was maintained ≤115 mmol/l for 10–12 days. After this period, hyponatremic rats and normonatremic controls fed the same diet without dDAVP were subjected to one of the following stimuli known to stimulate PRL release in rats: 3 min exposure to ether, hemorrhage (20 ml/kg), intravenous injection of 5‐hydroxytryptophane (5‐HTP, 10 mg/kg), or intravenous injection of estradiol (5 μg/kg). A baseline blood sample was collected before each stimulus, and 3–6 additional blood samples were collected at selected intervals after the stimulus. Baseline levels of plasma PRL were not different between normonatremic and hyponatremic rats. However, PRL responses induced by ether or estradiol, but not those induced by hemorrhage or 5‐HTP, were very significantly blunted in the chronically hyponatremic rats. Plasma AVP and OT responses were measured as an index of magnocellular secretion, but did not correlate with the PRL responses for any of the stimuli tested. Our results therefore demonstrate that ether‐ and estradiol‐induced PRL release can be osmotically inhibited, but the mechanisms underlying this inhibition appear to be relatively independent of effects on magnocellular AVP and OT secretion. This allows the possibility that either some parvocellular systems regulating PRL secretion are osmosensitive, or alternatively that other substances released from the neural lobe may selectively modulate pituitary PRL release in response t

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00585.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe relationship between vasopressin (VP) receptor levels in the anterior pituitary and VP‐stimulated ACTH release in vitro was studied in rats subjected to various chronic stress paradigms. The stress models used were water deprivation for 60 h and administration of 2% NaCI in the drinking water (both of which are associated with decreased pituitary ACTH responsiveness), and repeated i.p.hypertonic saline injections or repeated daily immobilization for 14 days (associated with increased ACTH responsiveness to novel stimuli). VP receptors were measured by binding of [3H]arginine‐VP to anterior pituitary membrane‐rich fractions, and ACTH responses to VP in collagenase dispersed anterior pituitary cells. In control rats, binding of [3H]AVP was saturable and high affinity, with a Kd of 0.45 ± 0.05 nM and a Bmaxof 138.8 ± 8.1 fmol/mg. In pituitary membranes from stressed rats, binding affinity was unchanged, but Bmaxchanged according to the type of stress. While VP binding was markedly reduced after water deprivation and 2% saline (25% and 49%, respectively), it was significantly increased after repeated i.p. hypertonic saline injections and repeated immobilization (126% and 154% of controls, respectively). The changes in VP binding were associated to parallel changes in maximum VP‐stimulated ACTH production in vitro, with a 34% decrease in water deprived rats and a 25% increase in hypertonic saline injected rats. The potentiating effect of VP on corticotropin releasing hormone‐stimulated ACTH was also reduced in cells from water‐restricted rats, and increased in cells from rats given repeated injections of hypertonic saline. The data show a direct relationship between changes in corticotroph responsiveness and changes in pituitary VP receptors during chronic stress, suggesting that pituitary VP receptor regulation is involved in the adaptation of the HPA axis during c

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00586.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractPerforated patch recording was used to examine the effect of the synthetic steroid dexamethasone on the whole cell potassium (K+) current, in the mouse corticotroph tumour cell line AtT20/D16‐16. In 15 out of 52 control cells (29%) there was a rapidly‐activating, rapidly‐ inactivating K+current of the A type, the amplitude of which was strongly dependent on the holding potential in use prior to its activation by depolarising voltage pulses, and which was blocked by 1 mM 4‐aminopyridine (4‐AP, n = 5). The effect of dexamethasone (100nM, 2h, 37°C) was that the A current increased in prevelance (24 out of 31 cells, 77%), lost its dependence on holding potential (over the range studied), and as a result became significantly larger than in controls, for certain voltage steps (peak A current density was 18.5 +2.4 pA/pF (n = 12) for control cells and 26.3 ± 3.9 pA/pF (n = 18) for dexamethasone treated cells, for a step to +30mV from ‐60mV, values are mean ± SEM). All cells exhibited a slowly‐activating, sustained K+current, which was unaffected by changes in the holding potential, unaffected by 4‐AP and consisted of at least 3 components: one blocked by 30 mM tetraethylammonium(TEA) or 100 nM charybdotoxin (CTX); a second blocked by 100 nM apamin; and a third not blocked by TEA, CTX, apamin, clofilium (100 nM) or niflumic acid (0.1 mM). Dexamethasone produced no change in the slowly‐activating, sustained current nor in any of its individual components. The effect of dexamethasone on the A current was completely blocked by 0.1 mM puromycin, a protein synthesis blocker, while puromycin alone did not affect the size or frequency of the A current, nor alter the slowly‐activating, sustained current. Secretion studies using 4‐AP confirmed that the A current has a role in stimulated adrenocorticotrophic hormone (ACTH) secretion. In summary, AtT20 cells contain at least four types of K+current: an A current and 3 currents contributing to the slowly‐activating current. Selective enhancement of the A current by dexamethasone, shown here to require synthesis of new protein, is one of the mechanisms whereby glucocorticoids exert inhibitory

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1994.tb00587.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY