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Biomedical subjects

S L Lightman

Publications and source records attributed to S L Lightman.

At least 91 records · Page 5Linked to original sources
PubMed1998

Hypertonic saline test for the investigation of posterior pituitary function.

The hypertonic saline test is a useful technique for distinguishing partial diabetes insipidus from psychogenic polydipsia, and for the diagnosis of complex disorders of osmoreceptor and posterior pituitary function. However, there is little information concerning its use in childhood. The experience of using this test in five children (11 months to 18 years) who presented diagnostic problems is reported. In two patients, in whom water deprivation tests were equivocal or impractical, an inappropriately low antidiuretic hormone (ADH) concentration (< 1 pmol/l) was demonstrated in the presence of an adequate osmotic stimulus (plasma osmolality > 295 mosmol/kg). In two children--one presenting with adipsic hypernatraemia and the other with hyponatraemia complicating desmopressin treatment of partial diabetes insipidus--defects of osmoreceptor function were identified. Confirming a diagnosis of idiopathic syndrome of inappropriate ADH secretion (SIADH) was possible in a patient with no other evidence of pituitary dysfunction. The hypertonic saline test was well tolerated, easy to perform, and diagnostic in all cases.

Adolescent↗
PubMed1998

The pulsatile characteristics of hypothalamo-pituitary-adrenal activity in female Lewis and Fischer 344 rats and its relationship to differential stress responses.

The dynamic patterns of basal and stimulated hypothalamo-pituitary-adrenal (HPA) activity of freely moving female Lewis and Fischer 344 rats were compared using an automated blood-sampling system. Both strains showed pulsatile corticosterone release throughout the 24 h cycle. Lewis rats showed clear circadian variation in both pulse frequency (8.4 +/- 0.4 pulses between 1700-2300 h vs. 5.3 +/- 0.8 pulses between 0500-1100 h; P < 0.05) and height (198 +/- 27 ng/ml between 1700-2300 h vs. 107 +/- 14 ng/ml between 0500-1100 h; P < 0.05). Fischer rats exhibited pulses of similar frequency and height to those in Lewis rats during the evening, but showed no circadian variation, resulting in higher mean daily corticosterone concentrations. Although both strains showed behavioral and HPA responses to white noise stress (10 min; 114 dB), Fischer rats showed much greater increases in total activity, grooming, and rearings, and two important differences in the corticosterone responses were observed. First, in Lewis rats a clear relationship existed between basal and stimulated HPA activities, in that a significant response was seen only when the stress coincided with the rising (secretory active) phase of a basal pulse. Noise stress coinciding with a falling (nonsecretory) phase elicited no significant response. In contrast, Fischer rats showed similar responses regardless of the underlying pulse phase. Second, after the peak response at 20 min (Lewis, 237 +/- 67 ng/ml; Fischer, 390 +/- 57 ng/ml), corticosterone levels fell rapidly in Lewis rats, but remained maximally elevated for 20 min in Fischer rats, resulting in a significantly greater integrated response. The corticosterone response to i.v. CRF was unaffected by pulse phase in both strains, suggesting that a suprapituitary mechanism mediates the phase-dependent response to stress in the Lewis strain. CRF-induced corticosterone levels rose more rapidly in Fischer rats, peaking at 10 min (473 +/- 95 ng/ml) compared with 30 min (390 +/- 75 ng/ml) in Lewis rats, suggesting greater pituitary sensitivity in this strain. Thus, differences in both central and pituitary control of the HPA axis contribute to the strain difference in stress responsiveness between female Lewis and Fischer rats.

Animals↗
PubMed1998

Ultradian rhythm of basal corticosterone release in the female rat: dynamic interaction with the response to acute stress.

The present study investigated the dynamic regulation of the hypothalamo-pituitary-adrenal axis and its significance to acute stress responsiveness in the female rat. An automated, frequent blood-sampling technique allowed the circadian rhythm of corticosterone to be resolved into a series of pulses. These were equally distributed (mean interval, 50.9 +/- 3.7 min) throughout the 24-h cycle, but their magnitude varied significantly, being higher between 1800-2200 h (137 +/- 9 ng/ml) than between 0600-1000 h (75 +/- 17 ng/ml). This pattern of release indicates continuous, but variable, activity of the axis throughout the day. The pulsatile ultradian rhythm suggested alternate periods of secretion and inhibition, which were found to have a profound effect on the corticosterone responses to acute stress. Noise stress (10 min, 114 decibels) evoked a transient increase in corticosterone, which reached a maximum (377 +/- 87 ng/ml) 20 min after onset. However, within this group (n = 26) the response varied depending on the underlying basal activity. When stress coincided with a rising (secretory) phase of a pulse, corticosterone concentrations rose to 602 +/- 150% of mean basal concentrations (P < 0.001). In contrast, when stress coincided with a falling (nonsecretory) phase of a pulse, a significantly smaller response, no greater than a basal pulse, was evoked. Thus, the alternate periods of secretion and inhibition generating basal hypothalamo-pituitary-adrenal activity are an important determinant of responses to acute stress.

Activity Cycles↗
PubMed1998

Serotonin depletion does not alter lipopolysaccharide-induced activation of the rat paraventricular nucleus.

We have investigated the effects of serotonin depletion on immune-mediated activation of the hypothalamo-pituitary-adrenal (HPA) axis. Corticotrophin-releasing factor (CRF) mRNA, c-fos mRNA and Fos peptide responses in the paraventricular nucleus (PVN) together with circulating levels of corticosterone were assessed in response to i.p. injections of three doses of lipopolysaccharide (LPS) both in control animals and animals pretreated with p-chlorophenylalanine (PCPA). Conscious animals received either an i.p. injection of 0.5 ml saline or 200 mg/kg PCPA in 0.5 ml saline on 2 consecutive days. This treatment resulted in a 93% depletion of serotonin on the fourth day. On day 4, animals received i.p. injections of LPS (2.5 mg/0.5 ml saline, 250 micrograms/0.5 ml or 50 micrograms/0.5 ml; E. coli 055:B5), or saline injections as controls. Pretreatment with PCPA had no effect on the basal levels of corticosterone, or on the elevated levels induced by the three doses, of LPS. Fos peptide and c-fos mRNA were undetectable in control animals, and Fos-like immunoreactivity increased in a dose-dependent manner following i.p. LPS in both control and PCPA-pretreated animals. C-fos mRNA expression induced by LPS was unaffected by serotonin depletion. Following the lowest dose of LPS, CRF mRNA did not change above control levels, however, the medium and high doses of LPS produced a significant (P < 0.05) increase in CRF mRNA levels in both depleted and intact animals. To confirm the temporal effects of serotonin depletion on activation of the HPA axis we collected plasma at 30 min, 1, 2, 3, 4, 5, and 6 h after LPS in both intact and serotonin-depleted animals. No significant differences in plasma corticosterone levels were found at any of the time points between intact and depleted animals. It appears that, at least under these experimental conditions, serotonergic inputs do not seem to play a major role in mediating the effects of LPS on changes in mRNA levels in the PVN or on the subsequent activation of the HPA axis.

Animals↗
PubMed1998

Adhesion molecules and relationship to leukocyte levels in allergic eye disease.

PURPOSE: To evaluate the conjunctival expression of leukocyte cell adhesion molecules (CAMs) and their relationship to leukocyte patterns on the microvasculature in the different clinical subtypes of allergic eye disease. METHODS: Immunohistochemical analysis, using appropriate monoclonal antibodies, was applied to glycolmethacrylate-embedded biopsies of bulbar and tarsal conjunctival tissue. The proportion of total blood vessels expressing a particular CAM was derived and related to individual cell types identified by cell-specific markers, such as mast cells, eosinophils, neutrophils, T cells, and macrophages. Statistical analysis was used to correlate adhesion molecule expression and, ultimately, cell type. RESULTS: There was a basal expression of intercellular adhesion molecule-1 (ICAM-1) (21% bulbar, 18% tarsal), E-selectin (15% bulbar, 21% tarsal), and vascular cell adhesion molecule-1 (VCAM-1) (13% bulbar and tarsal) in normal controls. In seasonal and perennial (bulbar and tarsal conjunctival) allergic tissue, ICAM-1 and E-selectin were expressed in 40% to 78% of vessels; in chronic disease, they were expressed in 45% to 80% of vessels; and in vernal giant papillae, they were expressed in as many as 90% of vessels. There was also increased expression of endothelial VCAM-1 in all forms of allergic eye disease; the greatest values were found in vernal giant papillae (64%). Biopsies taken in winter from seasonal sufferers demonstrated a marked reduction in levels of all three CAMs compared with those taken in the pollen season. This is almost consistent with values found in normal conjunctiva. Positive correlations were found between the levels of ICAM-1 and E-selectin expression and the degree of granulocyte and lymphocyte infiltration, although VCAM-1 expression correlated most closely with eosinophil numbers. CONCLUSIONS: Increased levels of cell adhesion molecules on the microvasculature and the factors that regulate them are likely to be responsible for the infiltration of cells bearing their ligands and may perpetuate inflammation in the chronic forms of allergic eye disease.

Adult↗
PubMed1997

Region-specific immediate-early gene expression following the administration of corticotropin-releasing hormone in virgin and lactating rats.

Central administration of corticotropin-releasing hormone (CRH) induces immediate-early gene (IEG) expression (c-fos and NGFI-B) in forebrain structures in a pattern similar to that observed following restraint stress. Lactating rats display modified neuroendocrine and behavioural responses to stress which have been hypothesized to be at least partially mediated through changes within the circuitry converging on the PVN, including CRH activated pathways. Quantitative measures of regional expression of c-fos and NGFI-B mRNA representative of two classical intracellular pathways, were used to define modification of the circuitry involved in the altered response to central CRH in the lactating female. Compared to saline controls, virgin female rats injected with 5 micrograms CRH i.c.v. displayed significantly increased immediate-early gene expression in the hypothalamic paraventricular nucleus (PVN), arcuate nucleus, lateral septum, bed nucleus of the stria terminalis, central, medial and cortical nuclei of the amygdala, and all subfields of the hippocampal formation. In lactating rats treated with CRH there was a significant increase in c-fos gene expression in the CeA and in the hippocampal subfields CA1, CA4 and dentate gyrus but not in the other areas examined. The i.c.v. administration of CRH significantly increased NGFI-B expression in the PVN, arcuate nucleus, medial amygdala and all hippocampal subfields of virgin rats. Lactating rats treated with CRH failed to show a significant increase in NGFI-B expression in the PVN, median eminence, arcuate nucleus, medial amygdala, CA2 and CA3 subfields of the hippocampus. These results further suggest that changes in specific neural circuits might at least partially underlie the modified responses to CRH and perhaps to stress in the lactating female.

Amygdala↗
PubMed1997

A nonviral vector system for efficient gene transfer to corneal endothelial cells via membrane integrins.

BACKGROUND: Genetic manipulation of allografts to suppress their ability to induce rejection is a promising approach for controlling rejection responses. A key to this approach is the development of appropriate DNA vectors. We are developing nonviral DNA vector systems based on synthetic peptides containing an integrin-binding segment for cellular targeting and a polylysine segment for DNA binding. METHODS: Two such peptides have been tested for their ability to deliver the beta-galactosidase reporter gene to the corneal endothelial cells of the rabbit, pig, and man. One peptide was derived from a phage display library, the other from the integrin-binding moiety of the toxin from the American pit viper, Crotalus molossus molossus. Corneas were cultured overnight and then exposed to the DNA/peptide vector under a variety of conditions involving different DNA concentrations, chloroquine concentrations, times of exposure, presence of serum, and presence of polyanion buffers. Expression of the beta-galactosidase gene was determined after 3 additional days in culture. Effects of the treatment on the viability of the endothelium were examined by confocal microscopy. RESULTS: We report that approximately 30% of corneal endothelial cells can be transfected with our optimal protocol using the molossin-based vector. Transfection is dependent on the presence of chloroquine and is inhibited by polyanion buffers such as HEPES. Viability of the corneal endothelium was excellent, except if corneas were incubated at high concentrations of chloroquine (0.5 mM) for prolonged periods (24 hr). CONCLUSIONS: Synthetic peptides containing both an integrin targeting and a DNA-binding moiety are promising as simple and highly versatile DNA vectors for use in corneal transplantation.

Animals↗
PubMed1997

The hypothalamic-pituitary-adrenal axis in autoimmunity.

We have characterized the activation of the HPA axis in the chronic inflammatory stress model of adjuvant-induced arthritis. Alteration in the hypothalamic control mechanism, where CRF is no longer the major corticotrophin-releasing factor, has been noted in a number of other immune-mediated disease models, including experimental allergic encephalomyelitis, eosinophilia myalgia syndrome, systemic lupus erythematosus, and leishmaniasis. These changes occur in both the mouse and the rat, suggesting this may be a common mechanism to chronic immune activation. We have good evidence to suggest that AVP takes over as the major stimulator of the axis. The arthritic rat is unable to mount a response to acute stressors, such as restraint or ip hypertonic saline. However, these animals are able to mount a response to an acute immune challenge. These data provide further evidence for a differential activation of the HPA by acute stress or acute immune stimulation. This presumably reflects an adaptive response to the development of chronic inflammation. We have demonstrated that central neurotransmitter systems are able to influence the severity of peripheral inflammation. In particular we have shown that depletion of serotonin at the time of the development of the inflammatory episode reduces the severity of the inflammation. These findings suggest the possibility of novel therapeutic strategies targeting neurotransmitter systems to alleviate inflammation.

Animals↗
PubMed1997

Characterisation of the normal conjunctival leukocyte population.

Lymphoid cells are present in normal mucosal tissue as scattered cells or organised into MALT. Knowledge of the non-pathological conjunctival lymphoid tissue is a vital basis for the further study of ocular surface inflammatory disorders. Therefore, we used immunohistochemistry to examine the leukocyte population of tarsal and bulbar conjunctiva from normal patients with no ocular or systemic inflammatory disease. CD3+ T cells were the most frequently occurring, and macrophages the second most frequently occurring, conjunctival cell type and were seen in the epithelium and substantia propria. There were greater numbers of leukocytes in the bulbar than in the tarsal area and this reached statistical significance for CD3+ T cells and CD57+ NK cells. In both bulbar and tarsal conjunctiva, B cells and neutrophils were seen in the epithelium and substantia propria, but plasma cells, NK cells and mast cells were present only in the substantia propria. No eosinophils were seen. CD8+ cells outnumbered CD4+ cells in the epithelium (CD4:CD8 0.3) but this was reversed in the substantia propria (CD4:CD8.1.3 tarsal, 2.0 bulbar). Most epithelial T cells and half the stromal T cells were CD45Ro+. IL-2R (CD25) staining was infrequent in the tarsal but not the bulbar area. The greater number and activation of T cells in the bulbar region may relate to greater antigen exposure. HLA-DR+ cells were mainly macrophages, but also included dendritic cells in the epithelium and a few epithelial cells. The conjunctival lymphocytes do have certain features of MALT cells, apart from mucosal recirculation, homing and promotion of sIgA production. Conjunctival IEL, like gut IEL, are predominantly CD8+, are found in the basal epithelium, are HML-1+, and have very high expression of CD45Ro. Substantia propria lymphocytes have more equal CD4 and CD8 numbers and frequently express CD45Ro. We found only one example of organised conjunctival lymphoid tissue in our study and suggest that the presence of CALT in humans is not universal.

Adolescent↗
PubMed1997

T-cell cytokines in chronic allergic eye disease.

BACKGROUND: The pathophysiology of chronic allergic eye disease cannot be explained by type I hypersensitivity alone, and T cell-mediated inflammation has been strongly implicated as a possible additional mechanism. Previous studies suggested that T(H2)-like T cells play an important role in one form of chronic allergic eye disease. OBJECTIVES: This study examined the cytokine profile of T cells in different clinical groups of subjects with chronic allergic eye disease (i.e., vernal keratoconjunctivitis [VKC], atopic keratoconjunctivitis [AKC], and giant papillary conjunctivitis [GPC]) and normal control subjects. METHODS: In situ hybridization was used to identify cytokine messenger RNA (mRNA), and two-color immunohistochemical analysis was used to demonstrate cytokine immunoreactivity localizing to T cells in the conjunctiva. RESULTS: Allergic tissue expressed increased levels of mRNA for IL-3, IL-4, and IL-5 when compared with normal tissue. There was significantly greater IL-2 mRNA expression in subjects with AKC than in those with VKC (p = 0.004) and those with GPC (p = 0.02). Immunoreactivity for T-cell IL-5 was present more frequently in subjects with VKC (p = 0.004), GPC (p = 0.02), and AKC (p = 0.04) than in normal control subjects. However, T-cell IFN-gamma protein expression was greater in subjects with AKC than in subjects with VKC (p = 0.01), GPC (p = 0.01), and control subjects (p = 0.005). CONCLUSIONS: These results show a T(H2)-like T-cell cytokine array in subjects with VKC and GPC but a shift in cytokine profile toward a T(H1)-like pattern, potentially because of differences in chronicity of the disorders, in subjects with AKC. These important functional T-cell variations in chronic allergic eye conditions are likely to be important in understanding differences in clinical characteristics and therapeutic responses.

Adolescent↗
PubMed1997

An antisense oligodeoxynucleotide complementary to corticotropin-releasing hormone mRNA inhibits rat splenocyte proliferation in vitro.

Expression of neuropeptides in immune tissues has been implicated in the paracrine control of immune functions. The effects of the endogenous splenic neuropeptide corticotropin-releasing hormone (CRH) on immune cell proliferation were investigated by incubating splenocytes from adult male Wistar rats in vitro with a specific antisense oligodeoxynucleotide probe complementary to CRH mRNA. Incubation of cells with 1 microgram/ml phosphodiester antisense probe for 24 h prior to stimulation with concanavalin A (Con A) resulted in a 30-65% decrease in 3H-thymidine uptake compared to controls. In spleen cells incubated with a random base sequence (nonsense) probe the uptake of 3H-thymidine was not different to that in control cells. Incubation of cells with either antisense or nonsense phosphorothioate-protected probes resulted in variable uptake of 3H-thymidine, demonstrating that these probes, unlike the phosphodiester probes, have non-specific effects on cells. Addition of synthetic CRH to the cells incubated with the antisense phosphodiester probe partially restored the proliferative response of splenocytes to Con A. Immunoreactive (ir) CRH measured by radioimmunoassay in splenocytes incubated with the antisense probe was significantly less than ir-CRH in splenocytes incubated with the nonsense probe or without probe, indicating that the expression of splenic CRH mRNA was specifically impaired. This attenuation of the cell proliferative response following reduced expression of splenic ir-CRH provides functional evidence for the involvement of endogenously synthesised immune ir-CRH in splenocyte activation.

Animals↗
PubMed1997

Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.

The ability of adenovirus (Ad) to transfect most cell types efficiently has already resulted in human gene therapy trials involving the systemic administration of adenoviral constructs. However, because of the complexity of brain function and the difficulty in noninvasively monitoring alterations in neuronal gene expression, the potential of Ad gene therapy strategies for treating disorders of the CNS has been difficult to assess. In the present study, we have used an Ad encoding the arginine vasopressin cDNA (AdAVP) in an AVP-deficient animal model of diabetes insipidus (the Brattleboro rat), which allowed us to monitor chronically the success of the gene therapy treatment by noninvasive assays. Injection of AdAVP into the supraoptic nuclei (SON) of the hypothalamus resulted in expression of AVP in magnocellular neurons. This was accompanied by reduced daily water intake and urine volume, as well as increased urine osmolality lasting 4 months. These data show that a single gene defect leading to a neurological disorder can be corrected with an adenovirus-based strategy. This study highlights the potential of using Ad gene therapy for the long-term treatment of disorders of the CNS.

Adenoviridae↗
PubMed1997

Intracellular calcium ion responses to somatostatin in cells from human somatotroph adenomas.

OBJECTIVE: Various GH secretory responses to long-acting somatostatin (SRIH) analogues have been observed during the treatment of acromegalic patients. The effects of SRIH on intracellular Ca2+ homeostasis in human somatotroph adenoma cells has not been examined in detail, and the underlying mechanisms therefore remain to be determined. Using isolated cells from human somatotroph adenomas, we have investigated the SRIH-induced intracellular Ca2+ responses at a single-cell level with computerized real time intracellular calcium ion (Ca2+i) imaging. PATIENTS: Adenoma specimens were obtained from 4 male and 11 female acromagalic patients (mean age 56, range 26-72 years) undergoing transsphenoidal hypophysectomy. METHODS: The identity of the biopsy material obtained was confirmed by Immunocytochemistry for hGH and in situ hybridization histochemistry using a 35S end-labelled hGH oligodeoxynucleotide probe and probes complementary to proopiomelanocortin and prolactin. Genomic DNA coding for somatostatin receptor (SSTR2) from each adenoma was PCR amplified and sequenced. Cells cultured from these adenoma were subject to computerized real time intracellular Ca2+i imaging at a single cell level. RESULTS: In cells from 11 of the 15 adenomas, SRIH produced a reversible, dose-independent reduction in [Ca2+]i from the mean of 167 +/- 11 to 43 +/- 3 nM within 51 +/- 1.8 s, and blocked the growth hormone releasing hormone (GRH)-induced increase in [Ca2+]i as expected. In the same adenomas, withdrawal of SRIH after a 30 second exposure produced a small but significant increase in resting [Ca2+]i. Pretreatment with pertussis toxin abolished the SRIH-Induced inhibition of [Ca2+]i and prevented the SRIH-induced inhibition of the effect of GRH on [Ca2+]i. One of the remaining 4 adenomas was completely unresponsive to SRIH despite responding vigorously to other ligands and Immunostaining strongly for GH. Surprisingly, cells from 3 adenomas showed a paradoxical increase in [Ca2+]i in response to SRIH in some or, in one case, all of the cells examined. In all adenomas the sequence of SSTR2 corresponded to wild-type. CONCLUSIONS: In the majority of cells derived from human somatotrophic adenomas, SRIH caused a reduction in baseline [Ca2+]i and inhibition of GRH-induced [Ca2+]i increase, as observed in somatotrophs of other species. In addition, SRIH was found either to induce a paradoxical increase in [Ca2+]i or to have no effect on [Ca2+]i in a small proportion of somatotroph adenomas examined. This finding corroborates the clinical observation that the response to SRIH analogues varies markedly between somatotroph adenoma patients. There was no evidence of SSTR2 mutations in any of the adenomas examined.

Acromegaly↗
PubMed1997

Endogenous neurotensin regulates hypothalamic-pituitary-adrenal axis activity and peptidergic neurons in the rat hypothalamic paraventricular nucleus.

Adrenocorticotropin (ACTH) secretion depends primarily on hypophysiotrophic factors released from neurons of the paraventricular nucleus of the hypothalamus. However, the neurochemical factors controlling these neurons, in particular neuropeptides, have had little investigation. In this study, we have investigated the role of neurotensin in the regulation of the different components of the hypothalamo-pituitary-adrenal (HPA) axis under basal and stress conditions in rats. For this purpose, animals were implanted with bilateral cannulae filled with crystals of the neurotensin antagonist, SR 48692, and which were located above the paraventricular nucleus. Five days after surgery, the effects of SR 48692 implants were studied on basal and stress-induced secretion of ACTH and corticosterone. Such treatment did not modify plasma levels of ACTH and corticosterone in basal conditions but reduced ACTH but not corticosterone levels after tail cut procedure. After an exposure to a novel environment for 30 min, both ACTH and corticosterone plasma levels were reduced in the SR 48692-treated group. In situ hybridization studies revealed that chronic administration of SR 48692 induced a significant reduction of CRF mRNA levels in the parvocellular division of the paraventricular nucleus of the hypothalamus. In addition, a 2-fold increase in basal levels of plasma vasopressin associated with an increase in vasopressin mRNA levels in the magnocellular neurons of the paraventricular nucleus was also detected. Finally, the basal plasma levels of oxytocin were not affected by the same treatment. Taken together, these findings strongly suggest that endogenous neurotensin in the paraventricular nucleus plays a tonic stimulatory role on HPA axis activity and an inhibitory effect on vasopressin secretion.

Adrenal Glands↗
PubMed1997

Endocrine and behavioural responses to noise stress: comparison of virgin and lactating female rats during non-disrupted maternal activity.

The behavioural and endocrine responses to a 10 min white noise stress have been characterized in female virgin and undisturbed lactating Sprague-Dawley rats. Animals were continuously video-taped and frequent blood samples were collected using an automated sampling system. Noise stress caused hypothalamo-pituitary-adrenal (HPA) activation, as indicated by a rapid increase in plasma corticosterone and ACTH in the virgins: corticosterone concentrations peaked 20 min after initiation of the stress before declining rapidly back to basal concentrations. In contrast, noise stress had no significant effect on either plasma corticosterone or ACTH concentrations in the lactating animals. However, 72 h after weaning the corticosterone response of the ex-lactating rats was of comparable magnitude, but longer duration to that seen in the virgins. Plasma prolactin concentrations were significantly higher in the lactating animals and declined in response to the noise whereas, a transient but reproducible increase was seen in the virgin group. In situ hybridization revealed a significantly lower basal expression of CRF mRNA in the paraventricular nucleus of lactating rats as compared to the virgins, but noise stress had no further effect. Virgin animals showed behavioural responses to the stress, including an increase in the total activity, exploratory behaviours (rearing) and displacement behaviours (grooming). Lactating animals also showed behavioural responses to the noise, but their activities were principally directed towards the pups. These data show that although lactating rats showed normal behavioural reactivity to a psychological stress they showed no statistically significant activation of the HPA axis, suggesting a dissociation of behavioural and neuroendocrine responses to this mild stress.

Adrenocorticotropic Hormone↗
PubMed1997

Rapid changes of heteronuclear RNA for arginine vasopressin but not for corticotropin releasing hormone in response to acute corticosterone administration.

Corticotropin-releasing hormone and arginine vasopressin gene transcription were studied in the parvocellular cells of the hypothalamic paraventricular nucleus in response to both adrenalectomy and the injection of corticosterone. Following 6 days ADX, there was an increase in AVP mRNA, AVP hnRNA and CRH mRNA but not CRH hnRNA. After injection of corticosterone in ADX rats there was an extremely rapid reduction in AVP hnRNA which fell markedly within 15 min. AVP mRNA, however, remained raised throughout the 4 h. CRH hnRNA fell at 2 and 4 h, while CRH mRNA was only significantly reduced at the 4 h time point. Data demonstrate markedly different kinetics for the glucocorticoid regulation of the AVP and CRH genes in the hypothalamus.

Adrenalectomy↗
PubMed1997

The neuroendocrine axis in patients with multiple sclerosis.

We investigated the basal and dynamic regulation of the hypothalamo-pituitary-adrenal (HPA), hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-gonadal axes and prolactin secretion in 52 patients with clinically definite multiple sclerosis. These patients also had gadolinium enhanced brain MRI scans and were divided into relapsing-remitting, secondary progressive and primary progressive subgroups. These subgroups were compared with healthy controls and a group of patients with other neurological diseases. The cortisol diurnal rhythm was preserved in all groups of patients. The time-integrated cortisol response to human corticotropin-releasing hormone (CRH) stimulation was lower in the patients with secondary progressive multiple sclerosis, compared with patients with primary progressive multiple sclerosis and healthy subjects. The time-integrated beta-endorphin response to CRH was greater in the patients with relapsing-remitting multiple sclerosis compared with the others. Feedback regulation assessed by dexamethasone suppression was normal. Serum testosterone was low in 24% of male multiple sclerosis patients and oestradiol was low in 25% of pre-menopausal female multiple sclerosis patients, whereas prolactin and the HPT function were normal. Correlations with C-reactive protein (CRP) and MRI suggest that activation of the HPA axis in multiple sclerosis patients is secondary to an active inflammatory stimulus.

Adult↗