Biomedical subjects

M E Bell

Publications and source records attributed to M E Bell.

At least 19 recordsLinked to original sources

PubMed2003

Chronic stress and obesity: a new view of "comfort food".

The effects of adrenal corticosteroids on subsequent adrenocorticotropin secretion are complex. Acutely (within hours), glucocorticoids (GCs) directly inhibit further activity in the hypothalamo-pituitary-adrenal axis, but the chronic actions (across days) of these steroids on brain are directly excitatory. Chronically high concentrations of GCs act in three ways that are functionally congruent. (i) GCs increase the expression of corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala, a critical node in the emotional brain. CRF enables recruitment of a chronic stress-response network. (ii) GCs increase the salience of pleasurable or compulsive activities (ingesting sucrose, fat, and drugs, or wheel-running). This motivates ingestion of "comfort food." (iii) GCs act systemically to increase abdominal fat depots. This allows an increased signal of abdominal energy stores to inhibit catecholamines in the brainstem and CRF expression in hypothalamic neurons regulating adrenocorticotropin. Chronic stress, together with high GC concentrations, usually decreases body weight gain in rats; by contrast, in stressed or depressed humans chronic stress induces either increased comfort food intake and body weight gain or decreased intake and body weight loss. Comfort food ingestion that produces abdominal obesity, decreases CRF mRNA in the hypothalamus of rats. Depressed people who overeat have decreased cerebrospinal CRF, catecholamine concentrations, and hypothalamo-pituitary-adrenal activity. We propose that people eat comfort food in an attempt to reduce the activity in the chronic stress-response network with its attendant anxiety. These mechanisms, determined in rats, may explain some of the epidemic of obesity occurring in our society.

Adrenal Glands↗

PubMed2003

A spoonful of sugar: feedback signals of energy stores and corticosterone regulate responses to chronic stress.

To begin to understand the effects of chronic stress on food intake and energy stores, the effects of increased activity in the hypothalamo-pituitary-adrenal (HPA) axis and glucocorticoids (GCs) on the body and brain must first be understood. We propose two major systems that are both GC sensitive: a metabolic feedback that is inhibitory and a direct central GC drive. Under basal conditions, the metabolic feedback signal to brain is dominant, although infusion of GC into a lateral brain ventricle blocks the effects of the metabolic feedback. Chronic stress activates GC secretion and brain nuclear GC receptor occupancy, markedly changing the normal relationships between these two major corticosteroid-activated systems. The stressor-induced switch in the relative strengths of these signals determines subsequent brain regulation of stress responses (behavioral, neuroendocrine and autonomic outflows). The metabolic feedback effects of GCs are mimicked by voluntary sucrose ingestion in adrenalectomized rats, and experiments suggest that the metabolic feedback also inhibits the stressor-induced direct GC drive on brain. We speculate that the interaction between peripheral and central GC-sensitive signaling systems may be coupled through the inhibitory actions of endogenous opiatergic inputs on corticotropin-releasing factor (CRF) neurons.

Adrenalectomy↗

PubMed2002

Sucrose intake and corticosterone interact with cold to modulate ingestive behaviour, energy balance, autonomic outflow and neuroendocrine responses during chronic stress.

In adrenalectomized (ADX) rats, either corticosterone replacement or increased sucrose intake will restore body weight gain, uncoupling protein-1, fat depot mass, food intake and corticotropin-releasing factor mRNA expression to normal. Here, we tested the potential interactions between sucrose intake and circulating corticosterone on behavioural, metabolic, autonomic and neuroendocrine responses to the stress of cold. Rats were left intact, sham-ADX, or ADX and replaced with pellets that provided normal, basal (30%B) or high stress (100%B) constant circulating concentrations of corticosterone +/- sucrose. More calories were consumed in cold than at room temperature (RT), provided that corticosterone concentrations were elevated above mean daily basal values in cold. Neither increased sucrose nor increased chow ingestion occurred in cold if the rats were ADX and replaced with 30%B. However, sucrose drinking in this group markedly ameliorated other responses to cold. By contrast, ADX30%B rats not drinking sucrose fared poorly, and none of the metabolic or endocrine variables were similar to those in sham-ADX controls. ADX100%B group in cold, resembled intact rats without sucrose; however, this group was metabolically abnormal at RT. We conclude that drinking sucrose lowers stress-induced corticosterone secretion while reducing many responses to cold; elevated corticosterone concentrations in the stress-response range are essential for the normal integrated cold-induced responses to occur.

Adipose Tissue↗

PubMed2001

Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis?

Both CRF and norepinephrine (NE) inhibit food intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH. Here, we show that ADX (but not sham-ADX) rats prefer to consume significantly more sucrose than saccharin. Voluntary ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to normal. Our results suggest that the brains of ADX rats, cued by sucrose energy (but not by nonnutritive saccharin) maintain normal activity in systems that regulate neuroendocrine (hypothalamic-pituitary-adrenal), behavioral (feeding), and metabolic functions (fat deposition). We conclude that because sucrose ingestion, like glucocorticoid replacement, normalizes energetic and neuromodulatory effects of ADX, many of the actions of the steroids on the central nervous system under basal conditions may be indirect and mediated by signals that result from the metabolic effects of adrenal steroids.

Administration, Oral↗

PubMed2000

Disruption of arcuate/paraventricular nucleus connections changes body energy balance and response to acute stress.

The mediobasal hypothalamus regulates functions necessary for survival, including body energy balance and adaptation to stress. The purpose of this experiment was to determine the contribution of the arcuate nucleus (ARC) in controlling these two functions by the paraventricular nucleus (PVN). Circular, horizontal cuts (1.0 mm radius) were placed immediately above the anterior ARC to sever afferents to the PVN. In shams the knife was lowered to the same coordinates but was not rotated. Food intake and body weight were monitored twice daily, at the beginning and end of the light cycle, for 1 week. On the final day the animals were restrained for 30 min. Lesioned animals had increased food intake in light and dark periods, higher weight gain per day, and more body fat as compared with shams. There was no difference in caloric efficiency. Unlike shams, lesioned rats had no predictable relationship between plasma insulin and leptin. Plasma ACTH was increased at 0 min in lesioned rats but was decreased 15 and 30 min after restraint as compared with shams. There was no difference in plasma corticosterone. Immunostaining revealed that alpha-melanocortin (alphaMSH) and neuropeptide Y (NPY) accumulated below the cuts, and both were decreased in PVN. Food intake and body weight were correlated negatively to alphaMSH, but not NPY in PVN. There was no difference in proopiomelanocortin (POMC) mRNA, but NPY mRNA was reduced in the ARC of lesioned animals. We conclude that ARC controls body energy balance in unstressed rats, possibly by alphaMSH input to PVN, and that ARC also is necessary for PVN regulation of ACTH.

Adrenocorticotropic Hormone↗

PubMed2000

Bottomed out: metabolic significance of the circadian trough in glucocorticoid concentrations.

Mild chronic stressors characteristically increase circadian trough corticosteroid concentrations in rats and man. The elevation in trough concentrations is often accompanied by a reduction in peak concentrations and no change in the daily mean values. Here we point out that elevation of trough glucocorticoids, probably through daily increases of glucocorticoid receptor occupancy, has major metabolic effects that bias organisms toward storage of calories as fat. Thus, chronic mild stress, by overriding the normal mineralocorticoid receptor-mediated corticosteroid feedback regulation of trough CRF and ACTH secretion, facilitates development of the metabolic syndrome.

Adrenal Cortex Hormones↗

PubMed2000

Corticosterone facilitates saccharin intake in adrenalectomized rats: does corticosterone increase stimulus salience?

Unlike normal rats, adrenalectomized rats do not voluntarily drink sweet saccharin solutions. To test whether this is a function of corticosterone in the circulation, and if corticosterone also increases the impetus for drinking saccharin after a period of withdrawal, we performed the following experiments. Young male rats were sham adrenalectomized (sham) or adrenalectomized (ADX); the ADX rats were provided with subcutaneous pellets containing (percent replacement of corticosterone, %B) 0%B, 15%B, 30%B or 100%B. Sham and ADX rats were immediately provided with saline (0.5%) and saccharin (2 mM) bottles in their home cages. Saccharin was allowed for 4 days on, 3 days off, 4 days on, 3 days off and a final day on, over the 15 days experiment. The dose of corticosterone determined both how much saccharin was voluntarily drunk by the ADX rats and the degree of overshoot after days off. Corticosterone also determined energy balance of the groups of ADX rats. The 30%B pellets restored food intake, body weight gain, insulin and caloric efficiency to the normal levels observed in sham rats. White fat depot weights and uncoupling protein concentration in brown adipose tissue were restored to sham levels by 100%B, suggesting that these variables which depend on activity in the sympathetic nervous system require considerable glucocorticoid receptor occupancy. We conclude that corticosterone increases the willingness to ingest sweetened water in a unimodal, dose-related manner, while moderate doses of corticosterone restore energy balance.

Adrenalectomy↗

PubMed2000

Voluntary sucrose ingestion, like corticosterone replacement, prevents the metabolic deficits of adrenalectomy.

We tested whether corticosterone replacement causes increased sucrose drinking in adrenalectomized (ADX) rats compared to sham-ADX (sham) rats. ADX rats given high doses of corticosterone drank as much sucrose as sham rats, whereas at three lower doses of corticosterone, drinking was similar between groups and was only approximately 40% of that ingested by shams. Compared to sham rats, ADX rats drinking saline, or saline and saccharin, gain weight more slowly, contain less white adipose tissue, and have higher sympathetic outflow as assessed by uncoupling protein content in brown adipose tissue. Allowing sucrose as well as saline to drink restored all of these variables to normal in ADX rats with no- or low-corticosterone. All endpoints from sucrose-drinking ADX rats with no-or low-corticosterone were indistinguishable from those in water-drinking shams. By contrast, sucrose-drinking ADX rats that were given high doses of corticosterone exhibited the usual catabolic effects of corticosterone on body weight gain and, unlike sucrose-drinking shams, were obese. We conclude that (i) high corticosterone stimulates the potability of sucrose and inhibits sympathetic stimulation of uncoupling protein; (ii) sucrose, without corticosterone, normalizes metabolic deficits in ADX rats probably through actions mediated both peripherally and by the central nervous system; and (iii) ADX rats have a distinct sucrose appetite.

Adipose Tissue↗

PubMed1999

Corticotropin-releasing factor receptor expression in the pituitary of fetal sheep after lesion of the hypothalamic paraventricular nucleus.

Both the capacity of CRF to release ACTH and the number of binding sites for CRF in the anterior pituitary decline during the final weeks of gestation in fetal sheep. The present study examined regulation of pituitary CRF receptor expression by the hypothalamic paraventricular nucleus (PVN) during late gestation in fetal sheep. Bilateral radiofrequency lesions of the PVN (PVN-Lx; n = 4) or sham lesions (SHAM; n = 5) were performed in fetal sheep at 118-122 days of gestational age (dGA). Pituitary glands from PVN-Lx and SHAM fetuses were collected at 139-142 dGA (term, approximately 148 dGA). Dual-label in situ hybridization was performed using a digoxigenin-labeled ovine POMC complementary RNA, together with a 35S-labeled ovine CRF type I (CRF1) receptor complementary RNA, to localize and quantify CRF1 receptor mRNA in POMC-hybridizing cells. Binding of [125I]-ovine CRF was also examined in the fetal pituitary of both PVN-Lx and SHAM fetuses using in situ autoradiography. The hybridization signal for the CRF1 receptor mRNA was primarily restricted to POMC-expressing cells in the anterior pituitary of both PVN-Lx and SHAM fetuses; no hybridization signal for the CRF1 receptor was observed in the neurointermediate lobe (NIL) in either group. The hybridization signal for CRF1 receptor mRNA in anterior pituitary corticotropes of PVN-Lx fetuses was significantly lower in both the inferior and superior regions of the anterior pituitary, compared with SHAM fetuses (P < 0.05). In the inferior region of the anterior pituitary, the percentage of POMC-hybridizing cells containing CRF1 receptor hybridization signal was significantly greater in PVN-Lx (90+/-7%; mean +/- SEM), compared with SHAM (67+/-6%; P < 0.05) fetuses. No differences in the percentage of POMC cells containing CRF1 receptor hybridization signal were observed in the superior region of the anterior pituitary between PVN-Lx (89+/-8%) and SHAM (87+/-9%). Binding of [125I]-ovine CRF (oCRF) was significantly greater in anterior pituitaries of PVN-Lx (140+/-19 mean arbitrary densitometry U +/- SEM), compared with SHAM (73+/-23; P < 0.05) fetuses. For both PVN-Lx and SHAM fetuses, there were no differences within group in [125I]-oCRF binding between the inferior and superior regions of the anterior pituitary. A weak, but significant (P < 0.05), autoradiographic signal for [125I]-oCRF binding was observed in the NIL of both SHAM and PVN-Lx fetal sheep. The level of [125I]-oCRF binding was significantly lower in the NIL, compared with anterior pituitary, for both SHAM (P < 0.01) and PVN-Lx fetuses. There were no differences in [125I]-oCRF binding in the NIL between SHAM and PVN-Lx fetal sheep. Our findings support a role for the PVN in regulating anterior pituitary CRF1 receptor expression in the late-gestation sheep fetus.

Animals↗

PubMed1999

Starvation: early signals, sensors, and sequelae.

To identify the sequences of changes in putative signals, reception of these and responses to starvation, we sampled fed and starved rats at 2- to 6-h intervals after removal of food 2 h before dark. Metabolites, hormones, hypothalamic neuropeptide expression, fat depots, and leptin expression were measured. At 2 h, insulin decreased, and FFA and corticosterone (B) increased; by 4 h, leptin and glucose levels decreased. Neuropeptide Y messenger RNA (mRNA) increased 6 h after food removal and thereafter. Adrenal and plasma B did not follow ACTH and were elevated throughout, with a nadir at the dark-light transition. Leptin correlated inversely with adrenal B. Fat stores decreased during the last 12 h. Leptin mRNA in perirenal and sc fat peaked during the dark period, resembling plasma leptin in fed rats. We conclude that 1) within the first 4 h, hormonal and metabolic signals relay starvation-induced information to the hypothalamus; 2) hypothalamic neuropeptide synthesis responds rapidly to the altered metabolic signals; 3) catabolic activity quickly predominates, reinforced by elevated B, not driven by ACTH, but possibly to a minor extent by leptin, and more by adrenal neural activity; and 4) leptin secretion decreases before leptin mRNA or fat depot weight, showing synthesis-independent regulation.

Adipose Tissue↗

PubMed1999

Warning! Nearby construction can profoundly affect your experiments.

This is meant to alert people to potentially major effects of construction projects on research results. Because we study the effects of stress on regulation of ACTH and corticosterone secretion and of serotonin receptors and stress on energy balance, we serve as an early warning system when things go awry. Most of our experiments include taking daily, or twice daily, measurements of rat or mouse weights and food intake as well as stress hormone levels. We are highly sensitized to environmental disruption and we've shown previously the effects of construction on stress hormones (1). However, we did not anticipate the change and disruption in energy balance that may occur in response to environmental perturbation. We provide two examples of these, below.

Animals↗

PubMed1998

Expression of proopiomelanocortin and prohormone convertase-1 and -2 in the late gestation fetal sheep pituitary.

The biological activity of fetal plasma immunoreactive ACTH has been reported to increase during the final weeks of gestation in fetal sheep, indicative of enhanced processing of POMC to ACTH. The present study was aimed at examining the expression and localization of the prohormone convertases, PC1 and PC2, in the pituitary of fetal sheep during the final weeks of gestation. Pituitaries were obtained from fetal sheep during the final 50 days gestation (dGA) at 100-107 dGA (n = 6), 117-121 dGA (n = 6), 126-130 dGA (n = 7), and 144-147 dGA (n = 8; term = approximately 148 dGA). Pituitaries were cryosectioned and subjected to dual labeling in situ hybridization using 35S-labeled PC1 and/or PC2 complementary RNA probes with a digoxigenin-labeled POMC complementary RNA to localize and quantify PC1 and PC2 messenger RNA (mRNA) in POMC-hybridizing cells. Immunocytochemistry was also performed to assess coexpression of PC1 and PC2 with ACTH in the fetal pituitary. PC1 mRNA was heterogeneously distributed in the anterior pituitary (AP) at all gestational ages examined, with hybridization signals observed over POMC-expressing cells (corticotropes) as well as over noncorticotrope phenotypes. The inferior region of the AP contained an approximately 3-fold greater (P < 0.01) percentage of POMC cells containing PC1 transcripts compared with the superior region of the AP. The proportion of POMC cells containing PC1 was significantly higher (P < 0.01) in the 100-107 dGA and 144-147 dGA groups than in the 117-121 dGA and 126-130 dGA groups in both inferior and superior AP. The intensity of the PC1 hybridization signal over POMC-expressing cells was also about 2- to 4-fold greater (P < 0.01) in the inferior compared with the superior region of the fetal AP; the intensity of the PC1 hybridization signal associated with POMC cells remained constant within the AP region and did not change over the gestational ages examined. Hybridization for PC1 was highly variable over regions of AP not hybridizing for POMC, probably due to differences in the level of mRNA for PC1 between phenotypes. Similar to POMC cells, the average hybridization signal for PC1 over non-POMC-hybridizing regions was about 2-fold greater in the inferior vs. superior AP. A weak PC2 hybridization signal was observed over a small number of unidentified phenotypes in the fetal AP at all ages examined; no POMC cells were found to contain PC2 hybridization signal. In the neurointermediate lobe, POMC, PC1, and PC2 were ubiquitously expressed at all ages. Levels of PC1 and PC2 mRNA in the fetal neurointermediate lobe did not change over the period of gestation examined. Immunocytochemical analysis of PC1 and PC2 with ACTH confirmed the pattern of expression and the extent of coexpression observed with in situ hybridization methods. We conclude that both PC1 and PC2 are likely to contribute to POMC processing in the fetal pituitary during the final weeks of gestation.

Animals↗

PubMed1997

Fetal sheep pituitary proopiomelanocortin in late gestation: effect of bilateral lesions of the paraventricular nucleus on regional and cellular messenger ribonucleic acid levels.

Previous experiments have clearly indicated that the successful completion of ovine gestation is dependent upon fetal adrenocortical maturation and the associated preterm rise in fetal plasma cortisol. The purposes of this study were to: 1) examine pituitary POMC messenger RNA (mRNA) levels during normal fetal development; and 2) examine the effects of bilateral lesion of the fetal paraventricular nucleus (PVN) on levels and spatial distribution of pituitary POMC mRNA. Pituitary glands were collected from intact fetal sheep of four gestational ages [100-107 days gestational age (dga), n = 8; 117-121 dga, n = 9; 126-130 dga, n = 9; 144-147 dga, n = 8]. Lesions of the PVN (PVN Lx; n = 4) or sham lesions (Sham; n = 5) were performed at 118-122 dga. Pituitary glands from PVN Lx and Sham fetuses were collected at 139-142 dga (term approximately 147 dga). POMC mRNA levels were determined by in situ hybridization. POMC transcript levels were determined by both regional analysis (20x magnification) and analysis of individual corticotropes (400x magnification). There was no difference among gestational age groups in superior anterior pituitary (AP) POMC mRNA levels determined by regional or cellular analysis. POMC mRNA levels were significantly greater in the inferior AP at 144-147 dga, compared with other gestational ages, using regional analysis (P = 0.003) or analysis of individual corticotropes (P < 0.01). POMC mRNA levels in the neurointermediate lobe in 126- to 130-dga fetuses were significantly greater than those in younger fetuses (P = 0.005) but not those in 144- to 147-dga fetuses. There was no difference in POMC mRNA levels in the superior AP between PVN Lx and Sham, using regional analysis or analysis of individual corticotropes. In the inferior AP, there was a significant decrease in POMC mRNA levels in PVN Lx, compared with Sham, using both regional analysis (P < 0.01) and cellular analysis (P < 0.01). There was no difference in POMC mRNA levels in the neurointermediate lobe as the result of bilateral PVN Lx. Our findings support that basal AP POMC mRNA levels are heterogenously distributed in the ovine fetal AP, with POMC mRNA levels in the inferior AP being significantly greater than in superior AP, by 144-147 dga. We further found that the higher POMC mRNA levels in the inferior AP reflect significantly higher corticotrope POMC transcripts and not simply a greater density of corticotropes in this AP region. The increase in POMC mRNA levels at 144-147 dga in the inferior AP seems unrelated to the onset of adrenocortical maturation (at approximately 125-130 dga). Finally, we report that increase in corticotrope POMC transcripts during late gestation in the inferior AP requires an intact PVN.

Animals↗

PubMed1991

Influence of reproductive state on pituitary-adrenal activity in the ewe.

Plasma corticosteroid concentrations are altered in pregnancy, during the reproductive cycle and by ovariectomy in many species. This study was designed to examine basal ACTH and cortisol in ewes of four different reproductive statuses: ovariectomized, nonpregnant cycling, nonpregnant noncycling, and pregnant. Blood samples were drawn every 4 hr for 48 hr from ewes during quiet, undisturbed conditions and analyzed for plasma ACTH, cortisol and progesterone concentrations. There were no significant changes in ACTH, cortisol or progesterone over time. Mean progesterone concentrations were significantly greater in the pregnant ewes than in all other ewes, and were greater in cycling ewes than noncycling or ovariectomized ewes. Mean ACTH was significantly greater in pregnant ewes than noncycling ewes, and mean cortisol was significantly greater in cycling ewes than in nonpregnant cycling or noncycling ewes. Ovariectomized ewes also had significantly greater mean cortisol concentrations than cycling ewes. The results demonstrate that there is an increase in basal ACTH and cortisol in ovine pregnancy.

Adrenocorticotropic Hormone↗

PubMed1991

Do plasma ACTH and cortisol concentrations in the late-gestation fetal sheep vary diurnally?

This study tested the hypothesis that fetal plasma ACTH and cortisol concentrations vary diurnally, and the mean concentration and the amplitude of the rhythm vary as a function of fetal gestational age. Nine chronically-catheterized fetal sheep were studied between 120 and 142 days' gestation. All of the fetuses were born spontaneously and alive. The pregnant ewes were maintained in a room with a regular light cycle (on at 07.30, off at 17.30). Food and water were available ad libitum. Blood samples were drawn at 4-h intervals throughout a 24-h period. There were no significant daily variations in fetal plasma ACTH, cortisol, or progesterone concentrations, except in the last 3 days of fetal life. In these fetuses ACTH and cortisol concentrations were increased in the afternoon and evening. We conclude that there is no diurnal rhythm in ovine fetal hypothalamo-pituitary-adrenal axis activity, and that the increased plasma concentrations of ACTH and cortisol in the afternoon and evening hours of the last few days of fetal life might be a response to increased uterine contraction activity.

Adrenocorticotropic Hormone↗

PubMed1990

Procaine isothiocyanate: an irreversible inhibitor of the specific binding of [3H]batrachotoxinin-A benzoate to sodium channels.

[3H]Batrachotoxinin-A benzoate ([3H]BTX-B) binds with high affinity to sites on voltage sensitive sodium channels in synaptoneurosomes from guinea pig cerebral cortex. Local anesthetics competitively antagonize the binding of [3H]BTX-B. An irreversible local anesthetic, procaine isothiocyanate (PRIT) and a tritiated derivative [( 3H]PRIT) have been prepared. PRIT inhibits the binding of [3H]BTX-B in a noncompetitive, irreversible manner (apparent Ki = 13 microM) whereas the parent compound, procaine, inhibits in a competitive, reversible manner (Ki = 40 microM). The dissociation rate of [3H]BTX-B from sites on the sodium channel is greatly accelerated in a concentration dependent manner in the presence of PRIT. A 50% increase in the dissociation rate of [3H]BTX-B is achieved in the presence of 0.98 microM PRIT. [3H]PRIT binds irreversibly to three proteins in synaptoneurosomes with apparent molecular weights of 20, 42, and 68 kDa. Protection studies with procaine and other local anesthetics suggest that only the 68 kDa species was related to local anesthetic binding.

Anesthetics, Local↗

PubMed1989

Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep.

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1988

Evidence for rapid inhibition of ACTH by corticosteroids in dogs.

These experiments were designed to determine whether stimulated adrenocorticotropic hormone (ACTH) secretion in dogs can be rapidly inhibited by increases in plasma corticosteroid concentrations. Five dogs were injected with a 2:1 mixture of cortisol to corticosterone (corticosteroids; total doses of 22.5, 45, or 90 micrograms/kg) or vehicle simultaneously with the injection of insulin (0.5 U/kg). These dogs were also injected with corticosteroids (45 micrograms/kg) with ovine corticotropin-releasing factor (oCRF-41; 1 micrograms/kg) or with the same dose of corticosteroids alone. Plasma ACTH and corticosteroid concentrations were measured for 90 min after the injections. The inhibition of ACTH secretion was significant 10 min after injection of oCRF-41 and 40 min after injection of insulin. The first significant increase in ACTH during insulin-induced hypoglycemia does not occur until 30 min, however. Therefore, after both of these stimuli to ACTH, the ACTH response is inhibited within approximately 10 min of its onset. The results suggest that canine ACTH responses to stimuli can be rapidly inhibited and that one site of this inhibition is the pituitary.

Adrenocorticotropic Hormone↗