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F J Tilders

Publications and source records attributed to F J Tilders.

At least 109 records · Page 6Linked to original sources
PubMed1987

Sympathoadrenal activity facilitates beta-endorphin and alpha-MSH secretion but does not potentiate ACTH secretion during immobilization stress.

The potential involvement of the sympathoadrenal system in stress-induced secretion of peptides from the intermediate lobe of the pituitary gland and the activation of the pituitary-adrenal axis was studied. Male Wistar rats were subjected to control procedures, to sympathectomy by chronic administration (8 weeks) of guanethidine and/or to medullectomy by adrenal enucleation 9 weeks prior to exposure to forced immobilization stress for various periods of time. In intact or sham-operated rats, immobilization caused a prompt increase of circulating norepinephrine, epinephrine (EPI), corticosterone and of immunoreactive adrenocorticotropic hormone (ACTHi), alpha-melanocyte-stimulating hormone (alpha-MSHi) and beta-endorphin (beta-ENDi). Peak levels of pituitary hormones were found after 10 min of stress exposure, but fell to less than 30% of these levels after 2.5 h of immobilization. Adrenal medullectomy, which abolished the stress-induced release of EPI, reduced the acute increase of plasma alpha-MSHi and beta-ENDi, but did not influence the acute increase of plasma ACTHi during immobilization stress. Also in medullectomized plus sympathectomized rats, the initial stress response of circulating ACTHi was not different from that of controls. Adrenal medullectomy with or without additional sympathectomy caused a marked increase in plasma ACTHi concentrations after prolonged stress exposure. We conclude that: catecholamines originating from the adrenalmedulla facilitate the stress-induced secretion of intermediate lobe peptides (alpha-MSHi, beta-ENDi); catecholamines from the sympathoadrenomedullary system do not contribute to the acute release of ACTH during immobilization stress; the sympathoadrenomedullary system is involved in the secondary reduction of circulating ACTHi levels seen during prolonged stress.

Adrenal Medulla↗
PubMed1987

Direct measurement of human plasma corticotropin-releasing hormone by "two-site" immunoradiometric assay.

A "two-site" immunoradiometric assay (IRMA) which allows the direct estimation of human CRH (hCRH) in plasma is described. Using this IRMA, basal levels of CRH in normal subjects ranged from 2-28 pg/mL [mean, 15 +/- 7 (+/- SD) pg/mL; n = 58]. Values in men and women were similar. Plasma CRH values within this range were also found in patients with Cushing's syndrome, Addison's disease, and Nelson's syndrome, with no correlation between plasma CRH and ACTH levels in these patients. Elevated plasma CRH levels were found in pregnant women near term [1462 +/- 752 (+/- SD) pg/mL; n = 55], and the dilution curve of this CRH-like immunoreactivity paralleled the IRMA standard curve. After its immunoadsorption from maternal plasma, this CRH-like material eluted on reverse phase high performance liquid chromatography with a retention time identical to that of synthetic CRH and had equipotent bioactivity with the synthetic peptide in the perfused anterior pituitary cell bioassay. Circulating CRH was not detected in Wistar rats, even after adrenalectomy and subsequent ether stress. Synthetic hCRH was degraded by fresh human plasma relatively slowly; 65% of added CRH remained after 1 h of incubation at 37 C. Degradation was inhibited by heat treatment (54 C; 1 h), cold treatment (4 C; 4 h), or freezing and thawing. Loss of synthetic rat CRH occurred more rapidly when fresh rat plasma was used; only 20% of added CRH remained under the same conditions. The inability to measure CRH in peripheral rat plasma may be due to the presence of active CRH-degrading enzymes which fragment the CRH molecule into forms not recognized by the CRH IRMA.

Addison Disease↗
PubMed1986

Corticotropin-releasing factor immunostaining in the rat spinal cord and medulla oblongata: an unexpected form of cross-reactivity with substance P.

By use of two antisera (alpha-CRFA, alpha-CRFB) raised against conjugates of o-CRF and bovine thyroglobulin, cryostat sections of formaldehyde-fixed gelatin models containing o-CRF can be stained. The staining intensity was quantitated by use of an automated microfluorimeter and was shown to be dependent on the concentration of o-CRF (1-300 microM) added to the gel. Determination of the CRF staining intensity after incorporation of o-CRF-related peptides and fragments indicated that both antisera reacted with the C-terminal region of o-CRF. They showed poor cross reactivity with r-CRF fixed in the gel. In the same models, r-CRF could be immunostained efficiently by use of an antiserum (alpha-CRFC) raised to a conjugate of r-CRF and thyroglobulin. This antiserum reacted with the N-terminal and midportion parts but not with the C-terminal fragment of o-CRF fixed in the gels. By use of both o-CRF antisera nerve fibers can be stained in the rat hypothalamus (median eminence) and in the medulla oblongata (spinal trigeminal tract and nucleus) and spinal cord (dorsal horn). Immunoinhibition experiments showed that o-CRF caused a concentration-dependent quenching (0.001-1 microM) of the immunostaining of o-CRF-containing models, rat median eminence and medulla oblongata preparations. alpha-CRFC also stained CRF immunoreactive (CRFi) fibers in the rat hypothalamus with an equal distribution to that found with the o-CRF antisera. However, no immunostaining was found in the spinal trigeminal nucleus and tract and in the dorsal horn, indicating that these fibers store different CRF-related products from those found in the hypothalamus. The CRFi in the medulla oblongata and spinal cord induced by alpha-CRFA was completely abolished 1 week after treatment of adult rats with capsaicin, a substance known to deplete Substance P (SP) from those areas. Gels incorporated with SP showed a concentration-dependent increase (range 10-1000 microM) in immunostaining with both o-CRF sera but not with the r-CRF antiserum. In addition, incubation of o-CRF sera with SP caused a concentration-dependent quenching (range 10-100 microM) of immunostaining in SP-containing models. SP at a concentration of 100 microM was also effective in quenching the CRFi in the dorsal horn and spinal trigeminal area. Quenching was also obtained with the C-terminal part of o-CRF (range 0.002-0.1 microM), which indicates that both CRF antisera contain an immunoglobulin which recognizes determinants on CRF as well as on SP.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1986

Colocalization of peptide histidine isoleucine amine and corticotropin-releasing factor immunoreactivity in neurons of the rat hypothalamus: a surprising artefact.

Indirect immunocytochemistry of corticotropin-releasing factor (CRF) and peptide histidine isoleucine amide (PHI) was performed by the use of antibodies raised to CRF and PHI. The staining intensity was quantitated by using an automated microfluorimeter. CRF and PHI immunoreactive fibres showed a similar pattern of distribution in the zona externa of the median eminence of the rat hypothalamus. Administration of colchicine (50 micrograms i.c.v.) resulted in the appearance of PHI and CRF immunoreactive cell bodies in the parvocellular part of the paraventricular nucleus. The PHI immunoreactive cell bodies were of low intensity and less abundant than those stained with the CRF antisera. Microfluorimetric measurements of the immunostaining in the median eminence showed parallel changes of PHI and CRF immunostaining after adrenalectomy, administration of reserpine and/or pargyline. In order to evaluate whether these data demonstrate that PHI and CRF are colocalized in hypothalamic neurons, we studied the specificity of PHI immunostaining by the use of a nonbiological gelatin model. Although CRF and PHI do not show structural homologies, the PHI antisera caused staining of PHI containing gels (range: 0.001-1 microM) but also of rat CRF (rCRF)-containing gels (range: 10-300 microM). In addition, preincubation of one of the PHI antisera with PHI or rCRF both caused a concentration-dependent quenching of the immunostaining in PHI- and CRF-containing gels and in preparations of the median eminence. Again, higher concentrations of rCRF (100 microM) than PHI (0.1 microM) were needed to show immunoinhibition, suggesting that the PHI antiserum has much lower avidity for native and fixed rCRF than for native and fixed PHI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Dopamine inhibits the release of immunoreactive beta-endorphin from rat hypothalamus in vitro.

Mediobasal hypothalamus tissue (MBH) from adult male rats was incubated in Krebs-Ringer bicarbonate medium (KRB). KRB was changed at 15 min intervals and the concentration of immunoreactive beta-endorphin (beta-ENDi) in the medium was measured by radioimmunoassay. Incubation of MBH tissue in normal KRB resulted in a constant release rate of beta-ENDi of approximately 1% of the tissue content per h. KRB containing 45 mM K+ causes a two fold increase in the release rate of beta-ENDi which was Ca2+ dependent. Dopamine (0.01-1.0 microM) inhibits both the spontaneous and the K+-stimulated release of beta-ENDi in a dose related manner. The dopamine receptor blocking agent haloperidol prevents this inhibitory effect of dopamine. The selective D-1 receptor agonist SKF 38393 does not affect the release rate of beta-ENDi; whereas the selective D-2 receptor agonist LY 141865 inhibits both the spontaneous and K+-stimulated release of beta-ENDi. The effects of LY 141865 can be blocked by (-)-sulpiride, a selective D-2 receptor antagonist. Norepinephrine only weakly inhibits the K+-stimulated release of beta-ENDi, an effect that can be blocked by haloperidol but not by the alpha-adrenoceptor blocker phentolamine. At concentrations tested (0.01-1.0 microM), isoproterenol, 5-hydroxytryptamine, carbachol and 8-Br-cAMP (1.0 microM) do not affect beta-ENDi release. It is concluded that dopamine can inhibit the release of beta-ENDi from hypothalamic neurons via a D-2 receptor mechanism.

Animals↗
PubMed1985

Stress-induced secretion of adrenocorticotropin in rats is inhibited by administration of antisera to ovine corticotropin-releasing factor and vasopressin.

Intact handled rats were pretreated with the immunoglobulin G fractions from normal rabbit serum or antisera to ovine corticotropin-releasing factor (CRF) and/or vasopressin and subjected to restraint or formalin stress. The formalin-induced rise in plasma ACTH was reduced to 28% in rats pretreated with anti-CRF, to 53% in those pretreated with antivasopressin, and to 16% in rats given both antibodies. Pretreatment of animals with anti-CRF, antivasopressin, or a combination of both antibodies also attenuated the ACTH response to restraint stress to 13%, 37%, and 12%, respectively, of those in normal rabbit serum-treated rats. Antiserum pretreatment did not reduce the restraint- or formalin-induced rise in plasma PRL in the same animals, however. We conclude, therefore, that both vasopressin and an ovine CRF-like peptide are physiologically relevant peptides involved in stress-induced ACTH release.

Adrenocorticotropic Hormone↗
PubMed1985

Role of epinephrine and vasopressin in the control of the pituitary-adrenal response to stress.

In addition to corticotropin-releasing factor (CRF) and structurally related peptides, arginine vasopressin (AVP), oxytocin, angiotensin II, vasoactive intestinal polypeptide, peptide histidine isoleucinamide, epinephrine (E), and norepinephrine induce secretion of adrenocorticotropin (ACTH) from corticotropic cells in vitro. The apparent affinity and intrinsic ACTH-releasing activity of these substances are lower than those of CRF. These substances can also act synergistically with CRF. In this paper the role of catecholamines and AVP in the control of ACTH release is discussed. Infusion i.v. of E increases plasma ACTH and corticosterone to levels that are normally found during stress. E-induced stimulation of pituitary-adrenal activity is mediated by beta adrenoceptors and involves release of CRF, because it can be prevented by beta-adrenoceptor blockers and by destruction of CRF neurons (hypothalamic lesions), blockade of CRF release (chlorpromazine, morphine, and Nembutal), or administration of CRF antiserum. Although stress can cause a vast increase in plasma E, circulating E is not essential for the acute stress-induced release of ACTH because blockade of beta (or alpha) adrenoceptors, administration of chlorisondamine, or extirpation of the adrenal medulla and sympathectomy do not prevent the pituitary-adrenal response to stress. In contrast, circulating E plays a major role in the release of intermediate-lobe peptides during emotional stress. Studies of the role of AVP in pituitary-adrenal control by the use of pressor receptor (V1) antagonists are not valuable because of the ineffectiveness of such antagonists in blocking AVP-induced release of ACTH from corticotropic cells in vitro. Treatment of rats with an antiserum to AVP reduces the ACTH response to stress. We conclude that AVP has an important role in stress-induced activation of the pituitary-adrenal system, possibly by potentiating the effects of CRF.

Adrenocorticotropic Hormone↗
PubMed1984

Quantitative immunocytochemistry of corticotropin-releasing factor (CRF). Studies on nonbiological models and on hypothalamic tissues of rats after hypophysectomy, adrenalectomy and dexamethasone treatment.

Indirect immunofluorescence cytochemistry of ovine corticotropin releasing factor (oCRF) was performed by use of an antiserum raised against a conjugate of oCRF and bovine thyroglobulin. The staining intensity was quantitated by use of an automated microfluorimeter. In cryostat sections of formaldehyde fixed oCRF containing gelatine models, the staining intensity was dependent on the concentration of oCRF (1-100 microM) added to the gel. Immunoinhibition experiments showed that oCRF induced identical concentration-dependent (0.001-1 microM) quenching of the immunostaining of oCRF containing models and rat median eminence (ME) preparations. Comparison of immunoinhibition of oCRF and ME extracts indicates that approximately 1.5 ng of CRF immunoreactivity (CRFi) is present in the ME of intact adult male Wistar rats. In the hypothalamus of rats, the majority of CRFi nerve fibers are localized in the external zone of the median eminence, whereas a large population of CRFi cell bodies is present in the paraventricular nucleus. Manipulations of the pituitary-adrenal system result in changes in the distribution of CRFi in these neurons. One week after extirpation of the adrenals or of the pituitary gland, the CRFi in the ME was reduced to 32 +/- 3% and 48 +/- 6% respectively. This decrease in CRFi in the median eminence can be largely prevented by treatment of rats with dexamethasone in doses that effectively reduce plasma ACTH and corticosterone levels. In contrast to intact rats, CRFi cell bodies can be visualized in the paraventricular nucleus of non-colchicine-treated rats after adrenalectomy or hypophysectomy. These data support the view that the hypothalamic CRFi neurons play a central role in the control of pituitary-adrenal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1984

The beta-adrenoceptor-blocking drug propranolol prevents secretion of immunoreactive beta-endorphin and alpha-melanocyte-stimulating hormone in response to certain stress stimuli.

Handled female Wistar rats were exposed to one of the following stress stimuli: restraint, electric foot shocks, passive avoidance situation, ether, or nembutal anesthesia followed by ip formalin or laparotomy. Trunk blood was collected 2-4 min after initiation of the stress stimulus for the determination of immunoreactive beta-endorphin (beta-ENDi), ACTH (ACTHi), and alpha-MSH (alpha-MSHi). All stressors evoked a rapid increase of circulating beta-ENDi to 0.75-2.10 ng/ml. All except passive avoidance situation also induced a rapid increase of plasma ACTHi to 0.45-0.70 ng/ml, whereas plasma alpha-MSHi increased after ether and restraint to 0.18-0.40 ng/ml but was not affected by formalin stress. To study the involvement of a beta-adrenoceptor mechanism in stress-induced peptide secretion, rats were treated with D-propranolol or L-propranolol 40 min before stress exposure. Propranolol did not prevent the increase of plasma ACTHi to any of the stressors studied. L-Propranolol but not its inactive D-isomer reduced (restraint, passive avoidance) or abolished (electric foot shocks) the increase in plasma beta-ENDi but did not affect the beta-ENDi response to other stressors (ether, formalin, laparotomy). Similarly, L-propranolol attenuated the alpha-MSHi response to restraint but not to ether stress. To discriminate between corticotroph or melanotroph origin of beta-ENDi released during stress, rats were treated with dexamethasone or were subjected to neurointermediate lobectomy (4 weeks). Neurointermediate lobectomy did not affect basal or stress-induced plasma ACTHi but resulted in undetectable alpha-MSHi levels. It largely prevented the beta-ENDi response to restraint stress (propranolol sensitive) but had little effect on the beta-ENDi response to formalin stress (propranolol insensitive). Conversely, dexamethasone prevented stress-induced ACTHi response without affecting plasma alpha-MSHi. The beta-ENDi response to restraint stress (propranolol sensitive) was not changed but the response to formalin stress (propranolol insensitive) was largely prevented by dexamethasone. These results show that the intermediate lobe is the main source of beta-ENDi secreted during exposure to stressors with a high emotional impact. Since intermediate lobe peptide secretion induced by such stimuli can be prevented by beta-adrenoceptor blockade, we speculate that stress-induced discharge of catecholamines, possibly from the adrenal medulla, is the trigger signal for peptide secretion from the melanotrophs during this type of stress.

Adrenocorticotropic Hormone↗
PubMed1983

Mapping of CRF-immunoreactive nerve fibers in the medulla oblongata and spinal cord of the rat.

By use of an antiserum raised against Corticotropin Releasing Factor (CRF 1-41), nerve fibers can be stained in the medulla oblongata and spinal cord of rats. A dense plexus of CRF-immunoreactive (CRFi) nerve fibers is present in the nucleus tractus spinalis nervi trigemini from which fiber bundles enter the tractus spinalis nervi trigemini. Large numbers of CRFi fibers are present in the substantia gelatinosa of the spinal cord, while the tractus solitarius, the nucleus tractus solitarius and the nucleus ambiguus contain a low number of CRFi fibers. In rats treated with colchicine, CRFi cell bodies are found in the hypothalamus and occasionally in the nucleus tractus solitarius and the nucleus olivaris inferior. Posterolateral deafferentation of the hypothalamus did not result in a disappearance of the CRFi fibers in the medulla oblongata and spinal cord 7 days after surgery. These results indicate that CRFi fibers present in the spinal cord and medulla oblongata are part of a novel peptidergic neuronal system, which is different from the hypothalamo-infundibular CRF system.

Animals↗
PubMed1983

Vasopressin is not involved in the catecholamine-induced release of ACTH, alpha-MSH and beta-endorphin from the rat pituitary gland.

The effect of catecholamines on plasma levels of immunoreactive ACTH (ACTHi), alpha-MSH (alpha-MSHi), beta-endorphin (beta-ENDi), arginine-vasopressin (AVPi) and of corticosterone (B) was studied in female rats. Intravenous infusion of the specific beta-adrenoceptor-stimulating agent l-isoproterenol in Wistar rats under pentobarbital anesthesia resulted in a dose-dependent (dose range: 10-100 ng/kg . min) increase in plasma B. At higher concentrations, l-isoproterenol also caused a dose-dependent increase in plasma AVPi (dose range: 100-1,000 ng/kg . min). In addition to isoproterenol, also intravenous infusion of l-epinephrine caused a dose-dependent increase of plasma B (dose range: 100-1,000 ng/kg . min), whereas l-epinephrine was without effect on plasma AVPi, even at the highest dose tested (1,000 ng/kg . min). The effect of l-epinephrine or l-isoproterenol on plasma B was associated with a parallel and dose-related increase in plasma ACTHi, beta-ENDi and alpha-MSHi. The increase of plasma ACTHi, B and beta-ENDi in response to l-isoproterenol (300 ng/kg . min) was identical in Wistar, Long Evans and Brattleboro rats (Long Evans rats with a hereditary lack of vasopressin). Also the responses to l-epinephrine (1,000 ng/kg . min) were identical in Wistar and Brattleboro rats. We conclude that vasopressin does not mediate the catecholamine-induced release of ACTH, beta-endorphin and alpha-MSH.

Adrenocorticotropic Hormone↗
PubMed1982

Immunoreactive beta-endorphin in the hypothalamus of female rats: changes in content and release during prepubertal development.

Female Wistar rats of different ages (1-45 days) were used. Extracts were made of the mediobasal hypothalamus (MBH) and beta-endorphin immunoreactivity (beta-ENDi) was quantitated by radioimmunoassay. Low but significant amounts of beta-ENDi (6.5 ng/MBH) were present on the first postnatal day. Hypothalamic beta-ENDi content did not change during the first week but decreased during the second week to a minimum (4.5 ng/MBH) on day 14. Thereafter, beta-ENDi increased rapidly to 13 ng/MBH on day 28 and remained at this level. Gel filtration showed that beta-ENDi substances with chromatographic characteristics identical to those of beta-END and beta-LPH were present in MBHs of 14-, 20- and 45-day-old rats. A beta-ENDi substance, possibly representing beta-END1-27, was nearly absent on day 14, but represented a major component of the MBH of the 45-day-old rat. In vitro incubation of MBH resulted in spontaneous release of beta-ENDi. Depolarization of neuronal membranes by incubation in medium containing 45 mMK+ stimulated beta-ENDi release. Both the spontaneous and K+-stimulated release of beta-ENDi were low on day 10 but reached postpubertal levels on day 20. These observations lead us to propose that the beta-ENDi-containing neurons in the hypothalamus of developing female rats rapidly mature between 14 and 20 days after birth. This may be causally related to the rapid decrease in circulating FSH levels that occurs during this period.

Aging↗
PubMed1982

Effect of hypothalamus lesions on the presence of CRF-immunoreactive nerve terminals in the median eminence and on the pituitary-adrenal response to stress.

By use of an antiserum raised against conjugated ovine corticotropin releasing factor (CRF1-41), nerve fibres can be stained immunocytochemically in the external zone of the median eminence of rats. The presence of CRF-immunoreactive (CRFi) nerve fibres and the plasma corticosterone response to ether stress were studied in rats 6-7 days after making various types of lesions in the hypothalamus. Complete anterolateral deafferentation of the mediobasal hypothalamus caused complete disappearance of CRFi fibres from the median eminence and blocked the corticosterone response to stress. Incomplete anterolateral hypothalamic deafferentation did not prevent the stress-induced increase of corticosterone and in these rats, part of the CRFi nerve fibres remained intact. A horizontal cut placed ventral to the paraventricular nuclei, completely prevented the corticosterone response in those rats that showed a complete disappearance of CRFi nerve fibres from the median eminence. Some rats however, still exhibited CRFi nerve fibres and these animals responded to stress with increased corticosterone levels. A similar horizontal cut made just dorsal to the paraventricular nuclei affected neither the corticosterone response to stress nor the appearance of CRFi nerve fibres in the median eminence. We conclude that the presence of CRFi nerve fibres in the median eminence is a prerequisite for rats to show a pituitary-adrenal response to ether stress and therefore represents the first functional evidence for the role of these hypothalamic CRFi-neurons.

Adrenal Glands↗
PubMed1982

In vitro release of LHRH from the hypothalamus of female rats during prepubertal development.

In this study changes in serum FSH concentration, hypothalamic LHRH content and in vitro release of LHRH from hypothalami of female Wistar rats during prepubertal development are described. The concentration of FSH in serum was determined by radioimmunoassay. Extremely high levels (1.800 ng/ml) were found between 12 and 16 days of age. Thereafter, FSH levels rapidly fell to low levels (135 ng/ml) on day 32. LHRH was measured by radioimmunoassay in extracts of mediobasal hypothalami (MBH) and showed a gradual increase during the first 10 days of life. Between 10 and 16 days of age, hypothalamic LHRH content did not change. After day 16, LHRH content sharply increased to a maximum found on day 32. The release of LHRH from MBH of developing rats was studied during in vitro incubation in Krebs-Ringer bicarbonate buffer. LHRH in the medium was measured by radioimmunoassay. The spontaneous release rate of LHRH was maximal from MBH of 12-day-old rats and minimal from those of 32 days. Depolarization of neural membranes, by medium containing 45 mM K+ induced a stimulation of LHRH release. This K+ -induced release of LHRH was also most prominent on day 12. These observations are consistent with the hypothesis that the high circulating FSH levels found in female rats between 12 and 16 days of age are at least in part caused by a high secretion rate of LHRH during this period.

Animals↗
PubMed1982

Adrenergic mechanisms involved in the control of pituitary-adrenal activity in the rat: a beta-adrenergic stimulatory mechanism.

Epinephrine or isoproterenol was infused into a lateral tail vein of female Wistar rats under Nembutal anesthesia. After 20 min of diffusion, trunk blood was collected for the determination of plasma corticosterone (B) and ACTH immunoreactivity (ACTHi). Infusion of l-epinephrine resulted in a dose-related increase in plasma ACTHi and B. Maximal levels were similar to those observed during ether stress. The pituitary-adrenal system appeared more sensitive than the cardiovascular system to epinephrine, since the ED50 values of epinephrine for its effects on ACTHi and heart rate were 165 and 840 ng/kg . min, respectively. The effect of epinephrine on pituitary-adrenal activity could be mimicked by the beta-adrenergic agonist l-isoproterenol and could be blocked by the beta-adrenergic antagonist l-propranolol, whereas d-propranolol was ineffective. The response of the pituitary-adrenal system to epinephrine was not caused by effects on peripheral parameters such as the distribution or clearance of ACTH or B but was mediated by an increase in ACTH release. The pituitary-adrenal response to epinephrine and isoproterenol was not related to changes in heart rate, blood pressure, or vasopressin secretion. Infusion of epinephrine at a dose that induced a maximal increase in plasma ACTHi and B (1000 ng/kg . min) resulted in a circulating epinephrine concentration of 11 pmol/ml, which is within the physiological range. From these data we conclude that 1) circulating epinephrine can stimulate pituitary-adrenocortical activity, 2) this action is mediated by a beta-adrenergic receptor mechanism, and 3) such a mechanism may be involved in the response of the pituitary-adrenal axis during certain forms of stress.

Adrenal Cortex↗