Predominant release of vasopressin vs. corticotropin-releasing factor from the isolated median eminence after adrenalectomy

In an in vitro system, we have demonstrated concomitant release of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) from the median eminence (ME) of normal and adrenalectomized rats. The ME were incubated in a Krebs-Ringer bicarbonate medium, CRF and AVP released into the medium were measured by radioimmunoassay. The release of both neuropeptides was stimulated by increasing concentrations of potassium (28-56 mM) in the incubation medium, or by addition of veratridine (5-20 microM). In both cases the release process was dependent on the presence of calcium in the incubation medium. Interestingly, potassium-induced release was found to be relatively insensitive to calcium channel antagonists that are potent inhibitors in smooth and cardiac muscle. The sodium channel antagonist, tetrodotoxin (1 microM), completely blocked the effect of veratridine, while no change was seen in the response to potassium. Adrenalectomy increased the ratio of AVP:CRF release from 2:1 in ME removed from sham-operated rats to 8:1 in ME from the adrenalectomized group. We suggest that this ratio of AVP:CRF release may also pertain in vivo, and that AVP could be the predominant corticotropic stimulus in adrenalectomized rats.     

Corticotrophin-releasing factor and arginine vasopressin fibre projections to the median eminence of fetal sheep

Using specific antibodies to corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) we have immunocytochemically located cells and fibres containing these peptides in sheep fetuses. CRF neurones were first detected, in low frequency, in the paraventricular nuclei of fetuses of 90 days of gestation (term is 142-152 days), although no connections to the median eminence (ME) were apparent until 105 days of gestation. AVP neurones were found from 42 days of gestation, the earliest stage examined, and at this age, fibres and terminals were present mainly in the external lamina of the ME. At subsequent ages there appeared to be a redistribution of AVP fibres such that by 132 days of gestation AVP projections were more or less equally distributed between the lamina of the ME, whereas in the adult AVP fibres are directed mainly to the internal lamina. The early appearance of AVP relative to CRF is consistent with the proposal that AVP may be a significant factor controlling adrenocorticotrophin release in the ovine fetus prior to 105 days of gestation.     

Effects of bilateral adrenalectomy on immunoreactive corticotropin-releasing factor in the rat median eminence and intermediate-posterior pituitary

Immunoreactive ACTH (I-ACTH) concentrations in the anterior pituitary (AP), intermediate-posterior pituitary (IP) and plasma, and immunoreactive corticotropin-releasing factor (I-CRF) concentrations in the median eminence (ME) and IP, were determined in adrenalectomized rats from 3 h till 14 days after surgery. Plasma I-ACTH concentrations showed the typical triphasic response over time. AP I-ACTH concentrations decreased immediately after surgery, then increased to high concentrations 3 days after surgery. I-ACTH concentrations in IP did not change through these periods. I-CRF concentrations in ME and IP decreased immediately after surgery, then gradually increased to high concentrations (ME) or to control levels (IP) 14 days after surgery. These results raise the possibility that the I-CRF in IP is of hypothalamic origin.     

Involvement of vasopressin in corticotropin-releasing effect of hypothalamic median eminence extract

Incubation of anterior pituitary (AP) fragments of rats was used to determine the specific role played by vasopressin (VP) in the overall effect of crude hypothalamic median eminence (HME) extract on ACTH release. Using the property of an AVP antiserum (AS) to completely abolish the CRF-like effect of hypothalamic VP without apparently affecting the effect of CRF, we show that under specific incubation conditions, the effect of the two secretagogues are additive at the pituitary level. ACTH secretion of pituitaries was enhanced when incubation was carried out in the presence of VP together with a maximum effective dose of VP-free HME extract (from Brattleboro rats). These observations favor the hypothesis that VP and CRF have different receptor sites in the anterior pituitary.     

Repeated stress-induced activation of corticotropin-releasing factor neurons enhances vasopressin stores and colocalization with corticotropin-releasing factor in the median eminence of rats.

Stress-induced release of corticotropin-releasing factor (CRF) and vasopressin (AVP) was studied in rats by measuring the decline of CRF and AVP stores in the median eminence after blockade of fast axonal transport with colchicine (5 micrograms per rat intracisternally). Quantitative immunocytochemistry was used to detect changes in CRFi and AVPi in the external zone of the median eminence (ZEME) selectively. Immobilization stress induced a fast ACTH response to 1,000-2,000 pg/ml which was associated with a fall in both CRFi and AVPi of 34% during the first 30 min. This is followed by different time courses of further AVPi and CRFi depletion. In addition, we investigated the effect of repeated daily stress exposure on CRFi and AVPi in the ZEM 1 day after stress exposure. Repeated daily immobilization for 9 or 16 subsequent days did not affect the CRFi stores in the ZEME, but increased the AVPi stores to 161 +/- 13% and 218 +/- 11% respectively. Quantitative analysis of electron microphotographs of repeatedly handled rats showed a mean density of CRF positive profiles in the ZEME of 45.5 +/- 2.5 per 500 microns 2 of which 25% also stained for pro-AVP-derived peptides. After 9 subsequent days of immobilization the total density of CRF-positive profiles remained unchanged, but the fraction of CRF swellings that also stained for pro-AVP-derived peptides increased approximately 2-fold. We conclude that (1) the secretion of AVPi and CRFi from the ZEME are independently controlled, indicating differential activation of AVP containing and AVP deficient CRF neurons during acute immobilization, and (2) repeated stress leads to plastic changes in hypothalamic CRF neurons resulting in increased AVP stores and colocalization in CRF nerve terminals.     

In vitro release of vasopressin and oxytocin from rat median eminence tissue

Release of vasopressin (AVP) and oxytocin (OT) from rat median eminence and posterior pituitary tissue was studied in vitro by incubation in Krebs-56 mM KCl buffer. Both total tissue content and releasable pool of each hormone was measured in control rats, adrenalectomized rats and dexamethasone-treated rats. Adrenalectomy resulted in significantly increased release of AVP, but not OT, from median eminence tissue, whereas dexamethasone treatment failed to affect release of either hormone. Neither treatment had any effect on AVP or OT release from posterior pituitary tissue. Similarly, neither treatment caused any significant changes in total median eminence or posterior pituitary AVP and OT contents relative to controls, although dexamethasone-treated rats had a significantly lower posterior pituitary OT content than adrenalectomized rats. KCl-stimulated hormone release from median eminence tissue most likely represents an estimate of AVP and OT in zona externa terminals rather than in zona interna axons, because release was blocked by CoCl2 indicating calcium-dependent exocytosis. Immunohistochemical staining of median eminence tissue correlated well with the results of in vitro hormone release, in that increased AVP staining in the zona externa of adrenalectomized rats was also the only significant change noted using this methodology. Since increased levels of releasable AVP in the median eminence probably reflects similarly increased AVP levels in the hypothalamo-hypophyseal portal vessels of adrenalectomized rats, these results support a potential physiologic role for median eminence AVP, but not OT, in the chronic stimulation of adrenocorticotropin hormone secretion following adrenalectomy.     

Central modulation of immunoreactive arginine vasopressin and oxytocin secretion into the hypophysial-portal circulation by corticotropin-releasing factor

Corticotropin-releasing factor (CRF), a potent ACTH secretagogue, has been found to exhibit many characteristics of central neurotransmitter/neuromodulatory substances. In this capacity, hypothalamic CRF might participate in postulated autoregulatory processes which regulate net secretion of adenohypophysical ACTH. We have examined the actions of centrally injected ovine CRF on the secretion of immunoreactive CRF, arginine vasopressin (AVP) and oxytocin (OT) into the hypophysial-portal circulation of urethane-anesthetized rats. Our observations do not support a short-term autoregulatory role for CRF. However, central administration of CRF was associated with a dose-dependent inhibition of hypophysial-portal concentrations of immunoreactive AVP and OT, suggesting potentially important central interactions among putative ACTH-regulatory factors.     

Subcutaneous administration of behaviorally effective doses of arginine vasopressin change brain AVP content only in median eminence

The accumulation of [8-arginine]vasopressin (AVP) in brain areas inside the blood-brain barrier (thalamus-hypothalamus, amygdala with overlying temporal cortex, hippocampus and cerebral cortex) and outside the blood-brain barrier (median eminence of the hypothalamus and area postrema) was measured after subcutaneous injection of the hormone. The plasma concentrations of AVP peaked at 5 min after subcutaneous injection and declined in a biphasic manner over the next 115 min. The concentration of AVP in brain tissue samples peaked at 20 min after the subcutaneous injection of AVP; the decline of AVP in the areas protected by the blood-brain barrier followed the time course seen for plasma. The concentration of AVP in the brain areas not so protected also peaked at 20 min but these declined at rates that differed from other brain areas and plasma. The concentration of AVP in the plasma and in most brain areas depended on the dose administered, while those in the median eminence and in the area postrema did not. Water deprivation for 24 and 48 h significantly elevated both the plasma AVP concentration and the concentration of AVP in the hypothalamus and in the amygdala-temporal cortex samples. The increases in AVP after water deprivation are limited to these two regions and are quantitatively much lower than after peripheral administration. Furthermore, when the brains of anesthetized rats were perfused free of blood, there were no changes in regional brain AVP content after subcutaneous treatment with 5,000 ng/kg of AVP, except for the median eminence. These data suggest that circulating AVP does not enter the parenchyma of brain areas protected by the blood-brain barrier in sufficient quantities to be detected by our assay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulus-induced corticotropin-releasing factor content and adrenocorticotropin release are augmented after unilateral adrenalectomy, independently of circulating corticosteroid levels

There is evidence for a neural link between the adrenal and hypothalamus that may mediate increased corticotropin-releasing factor and ACTH secretion within seconds after bilateral adrenalectomy. These studies on young male rats tested the possibility that functional evidence for adrenal afferent nerves might be revealed by the application of ACTH-releasing stimuli after the acute ACTH and corticosteroid responses to unilateral or sham adrenalectomy had subsided. Resting ACTH and corticosterone levels were not different in the two groups 1, 3, or 7-10 days after adrenal surgery. Despite similar initial conditions, the ACTH response to ether or to laparotomy with intestinal traction (but not to ip saline injections) was greater after unilateral adrenalectomy (P less than 0.01) at times when plasma corticosterone levels were not different. Hypothalamic corticotropin-releasing factor-like activity was higher in unilaterally adrenalectomized than in sham-operated rats 2 min after exposure to ether (P less than 0.05). We conclude that these results may represent a functional demonstration of decreased inhibitory neural feedback from the adrenal to the hypothalamus after unilateral adrenalectomy, and discuss the possibility that the absence of neural feedback may contribute to the well known hyperresponsiveness of bilaterally adrenalectomized rats to ACTH-releasing stimuli.     

Comparative immunoelectron microscopic localization of corticotropin-releasing factor (CRF-41) and oxytocin in the rat median eminence

Comparative ultrastructural localization of corticotropin-releasing factor (CRF) and oxytocin was performed in the rat median eminence of Long Evans and Brattleboro rats. The peroxidase-antiperoxidase technique used on serial ultrathin sections revealed CRF and oxytocin neurosecretory granule colocalization in the same fibers of the internal layer running towards the posterior pituitary. It is probable that both these peptides coexist in the same granules. In the Brattleboro rats, while genetically lacking vasopressin, CRF was nevertheless shown to be present. In these rats, as was demonstrated in the Long Evans rats, CRF distribution paralleled that of oxytocin only in the internal zone of the median eminence.     

Involvement of vasopressin in the down-regulation of pituitary corticotropin-releasing factor receptors after adrenalectomy

The role of vasopressin (VP) in the regulation of pituitary corticotropin-releasing factor (CRF) receptors was studied by examining the effects of adrenalectomy and VP infusion on pituitary CRF receptors in genetically VP-deficient rats (di/di) and Long-Evans control rats. Binding studies with [125I]Tyr-ovine CRF in 30,000 X g anterior pituitary membrane-rich fractions revealed similar characteristics for the CRF receptors in Long-Evans and di/di rats, with Kd values of 2.4 +/- 0.6 and 1.9 +/- 0.2 nM, respectively, and receptor concentrations of 278 +/- 31 and 286 +/- 43 fmol/mg, respectively. Two days after adrenalectomy, the pituitary CRF receptor concentration decreased by 72 +/- 4.2% in Long-Evans rats, but by only 20.3 +/- 5.6% in di/di rats. CRF receptor affinity was unchanged after adrenalectomy (Kd = 1.7 +/- 0.5 nM; n = 8). To determine whether VP deficiency is responsible for the smaller decrease in CRF receptor in di/di rats, the effect of exogenous VP infusion (100 ng/min) by sc osmotic minipumps was studied in adrenalectomized di/di rats. Two days after adrenalectomy, pituitary CRF receptors were reduced by 21 +/- 8% in control di/di rats, whereas a 77.7 +/- 1.8% decrease was observed in VP-infused di/di rats, comparable to the effect of adrenalectomy in Long-Evans rats. VP infusion also caused a significant 35 +/- 2% decrease in CRF receptors in the pituitaries of sham-operated di/di rats, with no change in CRF receptor affinity. In Sprague-Dawley rats, VP or CRF infusion (100 ng/min) decreased pituitary CRF receptors by 14 +/- 1.9% and 46 +/- 3%, respectively. However, the combined infusion of both peptides caused a 65% +/- 4.2 decrease, similar to that observed after adrenalectomy. In vitro incubation of quartered pituitaries with VP or CRF for 4 h reduced CRF receptors by 23.1 +/- 8.2% and 38.2 +/- 3.8%, respectively, while simultaneous preincubation with both peptides was followed by a decrease of 55.3 +/- 5.3%. These findings indicate that increased hypothalamic release of VP contributes to the down-regulation of pituitary CRF receptors after adrenalectomy.     

Central modulation of immunoreactive corticotropin-releasing factor secretion by arginine vasopressin

Arginine vasopressin (AVP) is regarded as facilitatory to adenohypophysial ACTH secretion at the level of the corticotropic cell. A central facilitatory action of AVP on hypothalamic corticotropin-releasing factor (CRF) has also been postulated, although conclusive evidence on this point is lacking. We directly tested this hypothesis and have found that intracerebroventricular administration of AVP attenuates secretion of immunoreactive CRF (irCRF) into the hypophysial portal circulation in urethane-anesthetized rats. This suppression occurred in a dose-dependent fashion. Conversely, immunoneutralization of AVP or treatment with an AVP antagonist increased portal concentrations of irCRF by 53% and 30%, respectively. These unexpected observations provide evidence for a tonic inhibitory role of central AVP in regulation of irCRF and thus ACTH secretion.     

Glucocorticoids regulate ovine hypophysial portal levels of corticotropin-releasing factor and arginine vasopressin in a stress-specific manner

Hypophysial portal circulation levels of immunoreactive (ir) CRF, immunoreactive arginine vasopressin (ir-AVP), and systemic ir-ACTH and cortisol were determined in dexamethasone-infused (20 micrograms/h) ewes, both under basal conditions and in response to audiovisual and hypoglycemic stress. Glucocorticoid infusion lowered mean basal levels of ir-CRF (P less than 0.05), ir-ACTH (P less than 0.05), and cortisol (P less than 0.05), but not of ir-AVP. Audiovisual stress led to coordinate release of ir-AVP and ir-CRF, and although the hypothalamic response to this stress was not altered in dexamethasone (DEX)-infused sheep, the pituitary-adrenal response was blocked, suggesting that glucocorticoids act on the pituitary rather than on higher centers to inhibit this response. In contrast, hypoglycemia led to preferential release of ir-AVP over ir-CRF, and DEX infusion delayed and inhibited both hypothalamic and pituitary responses. Ketamine injection also led to preferential release of ir-AVP, but neither the hypothalamic nor pituitary-adrenal responses were affected by DEX infusion. These results suggest that different stressors evoke different patterns of hypothalamic secretagogue release, and that glucocorticoids act in a site-specific fashion to regulate the hypothalamo-pituitary-adrenal responses to stress.     

Glucocorticoid implants around the hypothalamic paraventricular nucleus prevent the increase of corticotropin-releasing factor and arginine vasopressin immunostaining induced by adrenalectomy

The site of inhibitory action of glucocorticoids on the hypothalamic corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was studied using a combination of glucocorticoid implantation and immunohistochemistry. Adrenalectomy increased the number and the staining intensity of the neurons containing CRF-like immunoreactivity in the anterior and medial parvicellular subdivisions of the paraventricular nucleus (PVN) and induced the appearance of AVP-like immunoreactivity in the same cell population. These effects of adrenalectomy were inhibited only by those dexamethasone implants which were placed close to the PVN. Unilateral implantation of dexamethasone into the PVN inhibited the adrenalectomy-induced changes in CRF and AVP immunostaining only on the implanted side. Dexamethasone implants placed into the hippocampus decreased the effect of adrenalectomy in the PVN while similar implants into the amygdala and cerebral cortex were ineffective. These results suggest that the primary site of glucocorticoid feedback inhibition on the hypothalamic secretagogues of adrenocorticotropin is the PVN.     

Influence of the central nucleus of the amygdala on the content of corticotropin-releasing factor in the median eminence

The central nucleus of the amygdala possesses numerous neurons containing corticotropin-releasing factor (CRF). This study demonstrates a striking decrease of the CRF-like immunoreactivity in the median eminence at both 1 and 2 weeks after bilateral lesions of the amygdaloid central nucleus. Lesion of the amygdaloid central nucleus did not alter the neurophysin-like immunoreactivity in the internal zone of the median eminence, indicating the integrity of the efferent neurophysin-containing fibers of the supraoptic and paraventricular hypothalamic nuclei. However, there was a concomitant decrease of neurophysin and CRF-like immunoreactivity in the external zone of the median eminence. These results substantiate the hypothesis that the amygdaloid central nucleus can influence the content of CRF-like material in the median eminence via a multisynaptic pathway involving the synthesis of CRF at the level of the paraventricular nucleus of the hypothalamus. The exact mechanism by which lesion of the amygdaloid central nucleus influences the CRF content in the median eminence remains to be determined.     

Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo

A possible interaction between synthetic ovine corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was tested in anesthetized and in freely moving rats. In animals whose endogenous CRF release was blocked by chlorpromazine-morphine-nembutal, AVP elicited a significantly lower maximum ACTH response than did CRF, whereas the concomitant injection of both peptides resulted in a marked potentiation of CRF-induced ACTH secretion. In freely moving rats, AVP was more potent than CRF (on an equimolar basis) in elevating plasma ACTH levels. Since immunoneutralization of endogenous CRF by the administration of anti-CRF serum significantly reduced ACTH release due to injected AVP in these animals, we suggest that at least part of the AVP-induced ACTH secretion observed in nonanesthetized rats may be due to a potentiation of endogenous CRF by exogenously administered AVP. These data support previous reports of an in vitro synergism between CRF and vasopressin, and emphasize the complex role played by the interaction of these two peptides on ACTH release in vivo.     

The concentration of arginine vasopressin in pituitary stalk plasma of the rat after adrenalectomy or morphine

We have investigated the role of adrenal steroids and the opiates in regulating arginine vasopressin (AVP) secretion into the pituitary stalk blood of the rat. The portal plasma concentration of AVP in urethane-anesthetized male rats was 532 +/- 68 pg/ml (mean +/- SEM), while the peripheral plasma AVP concentration in intact urethane-anesthetized rats was 20.7 +/- 5.7 pg/ml. Column chromatography on Sephadex G-25 of an extract of a pool of portal plasma revealed that the material being assayed comigrated with synthetic AVP. Bilateral adrenalectomy (ADX) 5 days before the collection of portal blood elevated portal plasma AVP concentrations approximately 6-fold (655 +/- 124 pg/ml in controls vs. 4090 +/- 504 pg/ml in adrenalectomized animals). Dexamethasone administration (15 micrograms/kg X day) for 5 days prevented the ADX-induced increase in portal plasma AVP concentrations without significantly changing portal plasma AVP concentrations in intact rats. Portal plasma concentrations of beta-endorphin were not changed by ADX or dexamethasone treatment. The iv infusion of morphine sulfate (3 mg/kg) dramatically decreased the concentration of AVP in the portal plasma of the rat (501 +/- 101 pg/ml before morphine vs. 185 +/- 50 pg/ml after morphine). The inhibitory effect of morphine was reversed by naltrexone (1.0 mg/kg), whereas naltrexone alone did not alter AVP secretion. Morphine administration also decreased systemic plasma AVP concentrations in urethane-anesthetized rats (27.1 +/- 6.6 pg/ml in controls vs. 3.3 +/- 1.3 pg/ml in morphine-treated rats). Naltrexone treatment reversed this effect. These results suggest that AVP secretion into pituitary stalk blood is under the inhibitory influence of the adrenal steroids, and the increased concentration of AVP found in portal blood may be partially responsible for the elevated levels of ACTH after ADX. Furthermore, morphine-induced activation of the pituitary-adrenal axis is apparently independent of hypothalamic AVP secretion.     

Effect of dexamethasone on immunoreactive corticotropin-releasing factor in the rat median eminence and intermediate-posterior pituitary

Immunoreactive ACTH (I-ACTH) concentrations in the anterior pituitary, intermediate-posterior pituitary (IP), and plasma and immunoreactive corticotropin-releasing factor (I-CRF) concentrations in the median eminence and IP were determined in rats receiving dexamethasone for various periods from 16 h to 10 days. Plasma I-ACTH concentrations were decreased 16 h after a single injection of dexamethasone. Anterior pituitary I-ACTH concentrations did not decrease until 4 days after the start of dexamethasone medication. IP I-ACTH concentrations did not change throughout these periods. I-CRF concentrations in median eminence and IP rapidly decreased after dexamethasone administration. These results raise the possibility that the source of I-CRF in the IP is hypothalamic.     

Comparison of adrenocorticotropin control in Brattleboro, Long-Evans, and Wistar rats. Measurement of corticotropin-releasing factor, arginine vasopressin, and oxytocin in hypophysial portal blood

The purpose of this study was to compare the control of adrenocorticotropin (ACTH) and corticosterone secretion in homozygous Brattleboro rats with their syngeneic controls, Long-Evans rats, and with rats of the Wistar strain. Plasma concentrations of ACTH and corticosterone were measured by radioimmunoassay in trunk blood, and corticotropin-releasing factor 41 (CRF-41), arginine vasopressin (AVP), and oxytocin were assayed in hypophysial portal vessel blood. Portal plasma was extracted with methanol for CRF-41 determination, and four different antisera and several different high-performance liquid chromatography (HPLC) systems were used to investigate AVP release. The peripheral plasma concentrations of ACTH and corticosterone were significantly higher in Long-Evans and homozygous Brattleboro than in Wistar rats. This difference was due, at least in part, to an approximately twofold greater release of CRF-41 into hypophysial portal blood of the Long-Evans and Brattleboro compared with Wistar rats. There was no significant difference between the strains in the output of oxytocin into portal blood. While no AVP could be detected in the neural lobe of homozygous Brattleboro rats, a small amount of AVP-like immunoreactivity was detected in unextracted hypophysial portal blood from homozygous Brattleboro rats. However, this AVP-like immunoreactivity was clearly distinct from authentic AVP in several HPLC systems, had no antidiuretic activity, and on gel filtration had a relative molecular mass greater than 5 kD. In contrast, the AVP-like immunoreactivity in hypophysial portal blood from Long-Evans rats co-eluted with authentic AVP in all HPLC systems tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of corticotropin release during hypothermia: the role of corticotropin-releasing factor, vasopressin, and oxytocin

To investigate the mechanism by which ACTH secretion is inhibited during hypothermia, hypophysial portal blood was collected from euthermic and hypothermic rats, and the concentrations of corticotropin-releasing factor (CRF), vasopressin (AVP), and oxytocin (OT) were measured by RIA. Whereas CRF levels in portal plasma were not different in the two groups, AVP and OT levels were significantly lower in hypothermic rats. The concentration of AVP and OT in peripheral plasma was also significantly lower in hypothermic rats compared with euthermic controls. The pituitary responsiveness to CRF during hypothermia was tested in vivo and in vitro. In pentobarbital-anesthetized male rats injected iv with 0.1 or 1.0 nmol CRF, the ACTH response was significantly smaller in hypothermic compared with euthermic animals. However, hemipituitaries superfused at 31 C released the same amount of ACTH in response to 1 nM CRF as hemipituitaries superfused at 37 C (31 C, 541 +/- 90 pg; 37 C, 563 +/- 29 pg) despite reduced baseline secretion (31 C, 77 +/- 10 pg/10 min; 37 C, 114 +/- 14 pg/10 min; P less than 0.05). The data suggest that the inhibition of ACTH secretion during hypothermia is mediated by decreased hypothalamic secretion of AVP and OT which in turn decreases the pituitary responsiveness to CRF.