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R C Gaillard

Publications and source records attributed to R C Gaillard.

At least 55 records · Page 3Linked to original sources
PubMed1999

Food-dependent Cushing's syndrome: possible involvement of leptin in cortisol hypersecretion.

Stimulation ofcortisol secretion by food intake has been implicated in the pathogenesis of some cases of ACTH-independent Cushing's syndrome, via an aberrant response of the adrenal glands to gastric inhibitory polypeptide (GIP). We report here a novel case of food-dependent Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia. In this patient we were able to confirm a paradoxical stimulation of cortisol secretion by GIP in vivo as well as in vitro on dispersed tumor adrenal cells obtained at surgery. In addition to GIP, in vitro stimulation of these cultured tumor adrenal cells with leptin, the secreted product of the adipocyte, induced cortisol secretion. By comparison, no such stimulation was observed in vitro in adrenal cells obtained from another patient with bilateral macronodular adrenal hyperplasia and Cushing's syndrome that did not depend on food intake, in tumor cells obtained from a solitary cortisol-secreting adrenal adenoma, and in normal human adrenocortical cells. These results demonstrate that as in previously described cases of food-dependent Cushing's syndrome, GIP stimulated cortisol secretion from the adrenals of the patient reported here. Therefore, they indicate that such a paradoxical response probably represents the hallmark of this rare condition. In addition, they suggest that leptin, which normally inhibits stimulated cortisol secretion in humans, participated in cortisol hypersecretion in this case. Further studies in other cases of food-dependent Cushing's syndrome, however, will be necessary to better ascertain the pathophysiological significance of this finding.

Adrenal Glands↗
PubMed1998

The hypothalamo-pituitary-adrenal axis of athymic Swiss nude mice. The implications of T lymphocytes in the ACTH release from immune cells.

Because of the well-known role of the thymus in the regulation of immune function, we investigated whether the lack of thymus may affect hypothalamo-pituitary-adrenal (HPA) axis activity. Eight-week-old female Swiss nude (athymic) and BALB/c (normal) mice were used to study (a) the "in vivo" response of the HPA axis to various stresses and stimuli acting at either hypothalamic, pituitary, or adrenal levels and (b) the "in vitro" response of pituitary and adrenal cells to CRH and ACTH stimulation, respectively. The results indicate that (1) basal plasma ACTH levels were significantly (p < 0.05) higher in Swiss nude than in BALB/c mice, whereas basal corticosterone (B) levels were similar in both strains of mice; (2) the stress-induced release of ACTH and B in plasma was significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, regardless of the stimulus applied; (3) the "in vitro" pituitary response to CRH and the adrenal response to ACTH were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice; and (4) whereas hypothalamic CRH and pituitary ACTH contents were similar in both strains, adrenal B content was significantly (p < 0.05) lower in athymic mice. Immune reconstitution of the athymic nude mice by injecting splenocytes obtained from syngeneic heterozygous (i.e., immunologically fully competent) donors produced a significant increase in the B adrenal content of the nude mice. Among the splenocytes, CD4+ T-lymphocytes play a particularly important role in the release of ACTH from cells of the immune system. In conclusion, our results indicate that athymic nude mice have a blunted HPA axis response to various stresses and stimuli; this defect seems to reside at both the pituitary and adrenal levels. Immune reconstitution of the nude mice leads to a normalization of the adrenal B content.

Adrenal Glands↗
PubMed1998

Sex- and stress-steroids interactions and the immune system: evidence for a neuroendocrine-immunological sexual dimorphism.

It is well established that sexual dimorphism exits within the immune system. Females have higher levels of immunoglobulins, greater antibody response to antigens, and higher incidence of autoimmune diseases, such as systemic lupus erythematosus, Grave's disease, and Hashimoto thyroiditis than males. Spontaneous autoimmune syndromes in mice are more prevalent and of greater severity in females compared with males, and the course of the disease can be modulated by changes in levels of gonadal steroids. A sexual dimorphism is also present in the pituitary-adrenal function: females have higher corticosterone levels and higher corticosteroidogenesis. In the context of the immune-neuroendocrine interactions, we investigated the effects of gonadectomy and sex hormone therapy on endotoxin-stimulated hypothalamo-pituitary-adrenal axis. Whereas endotoxin-induced corticosterone release is invariable throughout the different stages of the oestrus cycle, gonadectomy in both male and female mice leads to enhanced adrenal and immune responses to endotoxin. Interestingly, these enhanced adrenal and immune responses can be completely reversed by testosterone treatment regardless of the sex of the mice. Studies performed over development confirm the role of endogenous testosterone in modulating the endotoxin-induced corticosterone secretion. Indeed, corticosterone response to endotoxin is maximal before puberty when endogenous testosterone levels are low and declines in postpubertal and adult mice. In conclusion, all these data support a sex steroid hormone basis for a neuroendocrine-immunologic sexual dimorphism.

Animals↗
PubMed1998

Stimulation by leptin of 3H GDP binding to brown adipose tissue of fasted but not fed rats.

OBJECTIVES: To assess the effects of intracerebroventricular (i.c.v.) leptin administration on rats fed ad libitum or fasted on 3H GDP binding to brown adipose tissue (BAT). SUBJECTS: Groups of 5-6 ten-week-old male Wistar rats. EXPERIMENTAL DESIGN: An i.c.v. cannula was inserted and unilateral denervation of interscapular brown adipose tissue (BAT) was performed 5 d before each study. Thereafter, leptin was infused i.c.v. during 72 h while rats were fed ad libitum or fasted. Vehicle-infused, pair-fed or fasted rats were used as controls. MEASUREMENTS: 3H GDP binding to innervated and denervated BAT mitochondria. RESULTS: 3H GDP binding to innervated or denervated BAT of rats fed ab libitum compared to vehicle-infused, pair-fed rats was not increased by i.c.v. leptin. 3H GDP binding was lower in fasted than in fed rats, and the difference was larger in innervated than denervated BAT. I.c.v. leptin increased 3H GDP binding by 30% in innervated, and by 51% in denervated BAT (P < 0.05) in fasted rats. CONCLUSIONS: I.c.v. leptin does not increase 3H GDP binding to BAT of rats fed ad libitum compared to pair-fed (food-restricted) rats. In contrast, i.c.v. leptin produces a mild stimulation of 3H GDP binding to BAT of fasted rats. This effect is not mediated by the sympathetic nervous system, because it is observed in both innervated and denervated BAT. These results are compatible with the concept that, in fasting rats, the decrease in leptin secretion contributes to the reduction in 3H GDP binding to BAT mitochondria.

Adipose Tissue, Brown↗
PubMed1998

Leptin inhibits directly glucocorticoid secretion by normal human and rat adrenal gland.

Different interactions have been described between glucocorticoids and the product of the ob gene leptin. Leptin can inhibit the activation of the hypothalamo-pituitary-adrenal axis by stressful stimuli, whereas adrenal glucocorticoids stimulate leptin production by the adipocyte. The present study was designed to investigate the potential direct effects of leptin to modulate glucocorticoid production by the adrenal. Human adrenal glands from kidney transplant donors were dissociated, and isolated primary cells were studied in vitro. These cells were preincubated with recombinant leptin (10(-10)-10(-7) M) for 6 or 24 h, and basal or ACTH-stimulated cortisol secretion was subsequently measured. Basal cortisol secretion was unaffected by leptin, but a significant and dose-dependent inhibition of ACTH-stimulated cortisol secretion was observed [down by 29 +/- 0.1% of controls with the highest leptin dose, P < 0.01 vs. CT (unrelated positive control)]. This effect of leptin was also observed in rat primary adrenocortical cells, where leptin inhibited stimulated corticosterone secretion in a dose-dependent manner (down by 46 +/- 0.1% of controls with the highest leptin dose, P < 0.001 vs. CT). These effects of leptin in adrenal cells are likely mediated by the long isoform of the leptin receptor (OB-R), because its transcript was found to be expressed in the adrenal tissue and leptin had no inhibitory effect in adrenal glands obtained from db/db mice. Therefore, leptin inhibits directly stimulated cortisol secretion from human and rat adrenal glands, and this may represent an important mechanism to modulate glucocorticoid levels in various metabolic states.

Adrenal Glands↗
PubMed1998

A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: determination of different sites of action.

Immune neuroendocrine interactions are vital for the individual's survival in certain physiopathological conditions, such as sepsis and tissular injury. It is known that several animal venoms, such as those from different snakes, are potent neurotoxic compounds and that their main component is a specific phospholipase A type 2 (PLA2). It has been described recently that the venom from Crotalus durissus terrificus [snake venom (SV), in the present study] possesses some cytotoxic effect in different in vitro and in vivo animal models. In the present study, we investigated whether SV and its main component, PLA2 (obtained from the same source), are able to stimulate both immune and neuroendocrine functions in mice, thus characterizing this type of neurotoxic shock. For this purpose, several in vivo and in vitro designs were used to further determine the sites of action of SV-PLA2 on the hypothalamo-pituitary-adrenal (HPA) axis function and on the release of the pathognomonic cytokine, tumor necrosis factor alpha (TNF alpha), of different types of inflammatory stress. Our results indicate that SV (25 microg/animal) and PLA2 (5 microg/animal), from the same origin, stimulate the HPA and immune axes when administered (i.p.) to adult mice; both preparations were able to enhance plasma glucose, ACTH, corticosterone (B), and TNF alpha plasma levels in a time-related fashion. SV was found to activate CRH- and arginine vasopressin-ergic functions in vivo and, in vitro, SV and PLA2 induced a concentration-related (0.05-10 microg/ml) effect on the release of both neuropeptides. SV also was effective in changing anterior pituitary ACTH and adrenal B contents, also in a time-dependent fashion. Direct effects of SV and PLA2 on anterior pituitary ACTH secretion also were found to function in a concentration-related fashion (0.001-1 microg/ml), and the direct corticotropin-releasing activity of PLA2 was additive to those of CRH and arginine vasopressin; the corticotropin-releasing activity of both SV and PLA2 were partially reversed by the specific PLA2 inhibitor, manoalide. On the other hand, neither preparation was able to directly modify spontaneous and ACTH-stimulated adrenal B output. The stimulatory effect of SV and PLA2 on in vivo TNF alpha release was confirmed by in vitro experiments on peripheral mononuclear cells; in fact, both PLA2 (0.001-1 microg/ml) and SV (0.1-10 microg/ml), as well as concavalin A (1-100 microg/ml), were able to stimulate TNF alpha output in the incubation medium. Our results clearly indicate that PLA2-dependent mechanisms are responsible for several symptoms of inflammatory stress induced during neurotoxemia. In fact, we found that this particular PLA2-related SV is able to stimulate both HPA axis and immune functions during the acute phase response of the inflammatory processes.

Adrenal Glands↗
PubMed1998

A regulatory loop between the hypothalamo-pituitary-adrenal (HPA) axis and circulating leptin: a physiological role of ACTH.

The product of the ob/ob gene, leptin, is known to be able to exert a modulator, role on HPA axis function. The aim of the present study was to determine whether endogenous ACTH and glucocorticoids exert any regulatory effect on leptin secretion. For this purpose bilaterally adrenalectomized (ADX) or sham operated (Sham) adult male rats were implanted with an indwelling i.v. catheter. A subgroup of ADX animals received, at the same time of surgery, a s.c. corticosterone (B) pellet (75 mg) (ADX+B). All animals were subjected to experimental designs 7 days after surgery. Our results indicate, as expected, that 7-day ADX animals have several fold increased basal ACTH plasma levels and non detectable circulating B, whereas ADX+B rats showed basal plasma ACTH levels in the range of Sham values and plasma B concentrations of about 5 microg/dl. Interestingly, basal plasma leptin levels were significantly (P < 0.05) decreased by 7 days post ADX, and B replacement therapy (ADX+B) restored circulating leptin to Sham levels. Acute dexamethasone (Dxmn, 30 microg/kg body weight, i.v.) treatment induced a very rapid decrease in plasma ACTH concentrations in both Sham and ADX rats, as well as a decrease in plasma B levels in Sham rats. Interestingly, Dxm test had no effect on plasma leptin levels in Sham animals; however, in ADX rats, the synthetic glucocorticoid increased plasma leptin concentrations, restoring the levels observed in Sham rats. This effect occurred at the same time when plasma ACTH levels were decreasing toward basal Sham values. These results clearly indicate that, beside the known effects of leptin on HPA axis function, circulating ACTH and glucocorticoid are able to modulate leptin secretion in plasma. The lack of circulating glucocorticoid and/or increased plasma ACTH concentrations, are responsible for decreasing leptin output, whereas decreased plasma ACTH concentrations allow an increase of leptin secretion in blood. Our data strongly support the existence of a closed, bi-directional, circuit between HPA axis function and adipose tissue metabolism. They further indicate the physiological relevance of different types of stress associated with many phenotypes of obesity.

Adrenalectomy↗
PubMed1998

Transcriptional activation of the macrophage migration-inhibitory factor gene by the corticotropin-releasing factor is mediated by the cyclic adenosine 3',5'- monophosphate responsive element-binding protein CREB in pituitary cells.

Macrophage migration-inhibitory factor (MIF) has recently been identified as a pituitary hormone that functions as a counterregulatory modulator of glucocorticoid action within the immune system. In the anterior pituitary gland, MIF is expressed in TSH- and ACTH-producing cells, and its secretion is induced by CRF. To investigate MIF function and regulation within pituitary cells, we initiated the characterization of the MIF 5'-regulatory region of the gene. The -1033 to +63 bp of the murine MIF promoter was cloned 5' to a luciferase reporter gene and transiently transfected into freshly isolated rat anterior pituitary cells. This construct drove high basal transcriptional activity that was further enhanced after stimulation with CRF or with an activator of adenylate cyclase. These transcriptional effects were associated with a concomitant rise in ACTH secretion in the transfected cells and by an increase in MIF gene expression as assessed by Northern blot analysis. A cAMP-responsive element (CRE) was identified within the MIF promoter region which, once mutated, abolished the cAMP responsiveness of the gene. Using this newly identified CRE, DNA-binding activity was detected by gel retardation assay in nuclear extracts prepared from isolated anterior pituitary cells and AtT-20 corticotrope tumor cells. Supershift experiments using antibodies against the CRE-binding protein CREB, together with competition assays and the use of recombinant CREB, allowed the detection of CREB-binding activity with the identified MIF CRE. These data demonstrate that CREB is the mediator of the CRF-induced MIF gene transcription in pituitary cells through an identified CRE in the proximal region of the MIF promoter.

Animals↗
PubMed1998

Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats.

We have previously shown that hexarelin, a novel GH-releasing peptide (GHRP), is able to elicit GH release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the effects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats. In the first experiment, adult male Sprague-Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 micrograms/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the mean +/- S.E.M. For both the peak and AUC results there was a significant (P < 0.05) difference in the GH response noted between the first (peak 301 +/- 37 ng/ml; AUC 5585 +/- 700 ng/ml per 30 min) and second (peak 149 +/- 47 ng/ml; AUC 3056 +/- 908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214 +/- 49 ng/ml; AUC 3862 +/- 844 ng/ml per 30 min). In a second series of experiments, adult male Sprague-Dawley rats received continuous infusions (100 micrograms/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not differ between any of the treatment groups, nor did any of the parameters of pulsatile hormone release analyzed. No significant differences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941 +/- 70 ng/ml) nor the 30 h (954 +/- 70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935 +/- 65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289 +/- 42 ng/ml; P < 0.05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of pulsatile GH release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

Analysis of Variance↗
PubMed1998

Cytokines in the neuroendocrine system.

Cytokines are important partners in the bidirectional network interrelating the immune and the neuroendocrine systems. These substances and their specific receptors, initially thought to be exclusively present in the immune system, have recently been shown to be also expressed in the neuroendocrine system. Cytokines can modulate the responses of all endocrine axes by acting at both the central and the peripheral levels. To explain how systemic cytokines may gain access to the brain, several mechanisms have been proposed, including an active transport through the blood-brain barrier, a passage at the circumventricular organ level, as well as a neuronal pathway through the vagal nerve. The immune-neuroendocrine interactions are involved in numerous physiological and pathophysiological conditions and seem to play an important role to maintain homeostasis.

Animals↗
PubMed1997

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia.

Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4-6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system.

Adipose Tissue↗
PubMed1997

Effect of chronic intracerebroventricular infusion of insulin on brown adipose tissue activity in fed and fasted rats.

OBJECTIVES: Carbohydrate feeding stimulates, and fasting decreases the sympathetic nervous system activity and brown adipose tissue (BAT) thermogenesis. This study was performed to assess the hypothesis that these effects were secondary to changes in insulin concentrations in the central nervous system. METHODS: BAT sympathetic activity was assessed by comparing 3H-GDP binding to isolated mitochondria of innervated and denervated interscapular BAT of three groups of 10 week old male Wistar rats: food-restricted, 48 h fasted or ad libitum fed. During the three days preceding this measurement, animals received a continuous intracerebroventricular (ivc) infusion of insulin (0.48 U/d) or vehicle. RESULTS: In food-restricted rats, 3H-GDP binding to mitochondria of innervated BAT was 41% higher than that to denervated BAT. Icv insulin did not stimulate 3H-GDP binding in innervated BAT. In 48 h fasted rats, 3H-GDP binding to mitochondria of innervated BAT was reduced by 30-50%, while the activity of denervated BAT was minimally affected. Icv insulin did not prevent this fasting-induced drop in BAT. In rats fed ad libitum, icv insulin decreased food intake by 17% (P < 0.05) and increased 3H-GDP binding to innervated BAT by 27% (P < 0.05). CONCLUSION: Intracerebroventricular insulin stimulates BAT activity in rats fed ad libitum but not in food-restricted or fasted rats. This demonstrates that the decrease in BAT activity observed during fasting is unlikely to be due to a decrease in insulin concentration in the nervous system.

Adipose Tissue, Brown↗
PubMed1997

Increased vasopressinergic activity as a possible compensatory mechanism for a normal hypothalamic-pituitary-adrenal axis response to stress in BALB/c nude mice.

A bidirectional relationship between the immune and neuroendocrine systems is now widely accepted. Since it is well known that the thymus plays an important role in the regulation of the immune function, we decided to explore whether a lack of the thymic function may influence hypothalamic-pituitary-adrenal (HPA) axis activity. Eight-week-old female mice of both strains, nude and control BALB/c, were used to study: (a) the in vivo response of the HPA axis to several stress stimuli acting at either the hypothalamic (insulin administration and ether vapor inhalation), pituitary (CRH and vasopressin injections) or adrenal (ACTH treatment) level and (b) the in vitro response of hypothalamic fragments to high KCl (48 mM) stimulation. The results indicate that: (1) basal plasma ACTH and vasopressin levels were significantly (p < 0.05) higher in nude than in control BALB/c mice, whereas basal plasma corticosterone concentrations were similar in both strains of mice; (2) although no significant strain-related difference in the stress-induced ACTH secretion in plasma was found, hypothalamic stimuli were able to induce a significantly (p < 0.05) higher secretion of glucocorticoid in plasma in nude than in control BALB/c mice; (3) the pattern of in vitro hypothalamic CRH release was similar in both strains of animals; however, basal AVP output and that stimulated by 48 mM KCl were significantly (p < 0.05) higher in nude than in control hypothalamic fragments, and (4) whereas hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid contents were similar in both strains, hypothalamic AVP content was significantly (p < 0.05) higher in athymic than in control mice. In summary, our results indicate that nude mice have an increased vasopressinergic function which could contribute to a normal HPA axis activity; thus, adult athymic mice of BALB/c origin could compensate, due to their increased vasopressinergic function, for a robust glucocorticoid release to protect themselves immediately after aggression. It remains to be determined whether this enhanced vasopressinergic function is a result of an early adrenal insufficiency due to congenital deficiency of thymic factors known to stimulate HPA axis function.

Adrenocorticotropic Hormone↗
PubMed1995

Sex and strain variability in the rat hypothalamo-pituitary-adrenal (HPA) axis function.

In the present investigation, we examined the influence of both genetic background and sex factors in the rat hypothalamo-pituitary-adrenal (HPA) axis function under both basal and post adrenalectomy (ADX) conditions. For these purposes adult female and male rats, from Sprague-Dawley (S-D), Fischer (F344/N), Lewis (LEW/N) and Buffalo (BUF) strains, were decapitated in basal condition or several (2, 7 and 14) days after ADX. Plasma stress hormones levels and adrenal corticosterone (B) concentration as well as peptide (ACTH, CRH and vasopressin, AVP) content in different tissues (anterior pituitary, AP; medial basal hypothalamus, MBH), were then evaluated by specific assays. Our results indicate that: a) despite no sex- and strain-related differences in AP ACTH and MBH ACTH secretagogues in basal condition, there exits a clear sexual dimorphism in plasma ACTH levels as well as in both plasma and adrenal B concentrations, with values significantly higher in females than in males, regardless the strain; b) ADX abolished plasma B levels and increased AP ACTH output in a time-dependent fashion up to the 14th day post surgery; c) AP ACTH content decreased 2 days after ADX, except in BUF female rats, thereafter tending to either recover or increase sham values by two weeks post ADX; d) ADX decreased MBH CRH at all periods studied, except in BUF female animals on day 14; e) ADX clearly diminished MBH AVP only in S-D rats, and f) a sexual dimorphism was also found in AP ACTH in 7-day-ADX S-D rats and in 14-day-ADX S-D and F344/N animals; also, a dimorphic pattern in MBH CRH was found in 7-day-ADX S-D as well as in 14-day-ADX F344/N and LEW/N rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Impaired hypothalamo-pituitary-adrenal axis function in Swiss nude athymic mice.

Various evidence suggests a bidirectional circuit between the immune and neuroendocrine systems. Because of the well-known role of the thymus in the regulation of the immune function, we designed this study to determine whether the lack of thymus may affect hypothalamo-pituitary-adrenal (HPA) axis activity by using both in vivo and in vitro paradigms in Swiss nude (athymic) and BALB/c (normal) mice. Eight-week-old female mice of both strains were used to study: (a) the in vivo response of the HPA axis to various stress stimuli acting at either hypothalamic (ether vapor inhalation, insulin administration), pituitary (CRH injection) or adrenal (ACTH treatment) level and (b) the in vitro response of pituitary and adrenal cells to CRH and ACTH stimulation, respectively. The results indicate that: (1) basal plasma ACTH levels were significantly (p < 0.05) higher in Swiss nude than in BALB/c mice, whereas basal plasma corticosterone (B) concentrations were similar in both strains of mice; (2) the stress-induced release of ACTH and B in plasma were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, regardless of the stimulus applied; (3) the in vitro pituitary response to CRH and the adrenal response to ACTH were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, whereas (4) hypothalamic CRH and pituitary ACTH contents were similar in both strains, adrenal B concentration was significantly (p < 0.05) lower in athymic mice; in addition, the nude mice adrenal glands were larger than those of BALB/c animals, due to marked hypertrophy of the zona fasciculata.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Repeated endotoxin treatment decreases immune and hypothalamo-pituitary-adrenal axis responses: effects of orchidectomy and testosterone therapy.

It is known that in vivo administration of bacterial endotoxin activates immune cells to release cytokines, these substances in turn enhancing hypothalamo-pituitary-adrenal (HPA) axis function; additional evidence supports the existence of an immune-neuroendocrine sexual dimorphism. In the present study, we investigated: (1) the in vivo response of both the HPA and the immune systems to single and repeated endotoxin administrations in mice, and (2) whether testosterone possesses a modulatory effect on neuroendocrine-immune function under endotoxemia. For these purposes, adult male BALB/c mice were orchidectomized (Odx) or sham-operated and injected s.c., on alternate days, with either corn oil alone (Odx and Sham) or containing 20 micrograms of testosterone (Odx+T) until animals were killed. One week after surgery, different groups of mice were treated i.p. with bacterial lipopolysaccharide (LPS; 25 micrograms per mouse) in a single (day 1, D1) or repeated (at 24-hour intervals for 5 consecutive days) form. Animals were decapitated (on D1, D3 and D5 of the treatment) 2 h after the last injection of either vehicle alone or containing LPS (the two groups were run in parellel). Trunk blood was collected and the whole medial basal hypothalamus (wMBH), the anterior pituitary (AP) and adrenal glands were dissected. Plasma tumor necrosis factor-alpha (TNF alpha), ACTH and corticosterone (B) concentrations as well as wMBH CRH, AP ACTH and adrenal B contents were determined by specific assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗