No differences in mucosal adaptive growth one week after intestinal resection in rats given enteral glutamine supplementation or deprived of glutamine

OBJECTIVE: To evaluate the effects of intraluminal glutamine on the adaptation of intestinal mucosa after resection compared with transsection and un-operated on control animals. DESIGN: Open, controlled, experimental study. SETTING: University hospital, Sweden. SUBJECTS: 123 Sprague-Dawley rats. INTERVENTION: Daily isonitrogenous oral diet was given either free of glutamine or supplemented with 4% glutamine for 2 or 7 days to rats subjected to intestinal resection, transection or no operation. MAIN OUTCOME MEASURES: Body weight and protein content, DNA content, and thymidine incorporation in jejunal and ileal mucosa. RESULTS: Resection resulted in a significant growth stimulation evaluated by weight/body weight, protein, and DNA content (p < 0.05-0.001). Glutamine supplementation did not significantly influence this growth response. Thymidine incorporation in jejunum was stimulated by glutamine on day 3 (p < 0.05-0.001). CONCLUSION: The glutamine fortified diet had no growth stimulating effects compared with a glutamine free diet one week after 60% intestinal resection. An early increase in thymidine incorporation indicated that glutamine had a transient proliferative effect.     

Different responses of apolipoprotein A-I, A-IV, and B gene expression during intestinal adaptation to a massive small bowel resection in rats

Gene expression of apolipoproteins (apo) A-I, A-IV, and B, the predominant protein components of chylomicrons, was investigated in the residual ileum after a massive small bowel resection in rats. A Northern blot analysis showed that the apo A-IV mRNA level, but not the apo A-I and B mRNA levels, in the ileum was significantly higher in the resected rats than in the sham-operated rats 24 h and 2 wk post-surgery. RT-PCR coupled with a primer extension assay revealed that the apo B-48 mRNA/apo B-100 mRNA ratio, i.e., apo B mRNA editing, in the ileum was unchanged by the resection. It is thus concluded that, among the major intestinal apolipoproteins, apo A-IV is the only one whose gene expression is influenced by loss of the proximal intestine.     

Comparative effect of growth hormone and plerocercoid growth factor in the intestinal resection in rat

OBJECTIVE: After massive bowel resection, absorption depends on how fast the mucosal adaptation takes place. This work aims at assessing the trophic effect of growth hormone (GH) and its analogue, the plerocercoid growth factor (PGF), on the intestinal mucosa after 90% small bowel resection. EXPERIMENTAL DESIGN: 24 male Wistar rats were divided into four groups of 6: Control (laparotomy), 90% small bowel resection (RID), resection and treatment with GH during 14 days (RID + GH) and resection and PGF treatment (RID + PGF). Intestinal mucosal adaptation was assessed by measuring mucosal weight and height, and evaluating the regenerative activity by measuring proliferation cell nuclear antigen (PCNA) labelling index. RESULTS: Bowel resection itself caused a significant increment of jejunal and ileal mucosal height in comparison with the control group. GH and PGF did not change this increase. Jejunal and ileal proliferation indexes were significantly higher than those in controls and they were significantly higher in both RID + GH and RID + PGF groups. CONCLUSIONS: GH and PGF cause a proliferative effect on the intestinal mucosa, even in hyperproliferative states such as the small bowel resection. This finding might have a clinic application.     

Dietary supplementation of nucleotides and arginine promotes healing of small bowel ulcers in experimental ulcerative ileitis

We previously showed that intravenous total parenteral nutrition supplemented with nucleosides and nucleotides (NS/NT) promoted ulcer healing in rats with indomethacin-induced ileitis. The present study evaluated whether dietary NT supplementation would similarly affect ulcer healing in this model. Female Lewis rats were randomized into either control or experimental groups receiving yeast RNA containing NT or arginine, glutamine, fish oil, guar gum, or a combination of yeast RNA+arginine diets. Ileitis was induced by two doses of indomethacin (7.5 mg/kg) administered subcutaneously 24 hr apart. Ulcer number and length were determined at 4, 8, and 14 days after induction of ileitis. Ileal villous and crypt length, crypt-villous ratio, and bromodeoxyuridine (BrdU) labeling were studied in the control and yeast RNA-supplemented diet groups. Ileal ulceration was present in all groups at 4 and 8 days and was almost healed by 14 days. Rats receiving yeast RNA, arginine, and yeast RNA + arginine diets showed a significant decrease in ulcer number (56%, 28%, and 34%, respectively) and length (67%, 41%, and 48%, respectively) compared to controls at 8 but not at 4 days. Glutamine, fish oil, and guar gum had no effect on ulcer healing at 4, 8, or 14 days. Among the histological parameters, a significant decrease in crypt length in the yeast RNA-supplemented group at 8 days suggested an acceleration of the healing process and restoration to a near-normal crypt-villous architecture. We conclude that the yeast RNA, arginine, and yeast RNA + arginine diets accelerated ulcer healing, as indicated by decreased ulcer number and length. We postulate that the underlying mechanism(s) contributing to ulcer healing may be related, in part, to increased cell proliferation.     

Supplemental dietary arginine accelerates intestinal mucosal regeneration and enhances bacterial clearance following radiation enteritis in rats

Medetomidine was administered to sheep and horses at a dose rate of 5 microg kg(-1) (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha1 adrenoceptor antagonist; 100 microg kg(-1), i.v.) had no effect on the cardiovascular response to medetomidine (5 microg kg(-1), i.v.), but inhibited the cardiovascular response of methoxamine (an alpha1 adrenoceptor agonist; 75 microg kg(-1), i.v.). L-659,066 (an alpha2 adrenoceptor antagonist which does not cross the blood brain barrier; 264 microg kg(-1), i.v.) attenuated the medetomidine induced bradycardia, but had no effect on the cardiovascular response to methoxamine. L659,066 also reduced the medetomidine induced hypertension in sheep, but had less effect on the horse. It is concluded that both alpha1 and alpha2 adrenoceptors are important in the control of cardiovascular function in horses and sheep. Medetomidine appears to act on alpha2 adrenoceptors alone in the sheep. The cardiovascular effects of medetomidine in the horse are complex and may be influenced by central alpha2 adrenoceptor regulation or effects on other receptor subtypes as well as direct stimulation of peripheral alpha2 adrenoceptors.     

Effect of ageing on pancreatic hyperplasia after 90% proximal small bowel resection

PURPOSE: A longitudinal study to ascertain the attitudes toward, and habits of, substance use among a single class of medical students. METHOD: A single class from a northeastern medical school was surveyed in both its first year (February 1991, 176 students) and its third year (May 1993, 170 students). The students were asked to report how frequently during the prior year they had used drugs or alcohol, and whether their use of each substance had increased, decreased, or remained the same since entering medical school; to identify any family members with histories of alcohol or drug problems; and to report any incidence during the prior year of ten behaviors associated with substance dependence. The students were also asked to indicate their agreement or disagreement with 11 attitudinal statements. Additional attitudinal items asked the students to identify three major deterrents to the abuse of drugs and alcohol, and what they had done if they had become aware of a classmate with a drug or alcohol problem. Chi-square analysis and two-tailed t-tests were used to compare data from the two surveys. RESULTS: The response rates in the first and second surveys were 96.9% and 81.8%, respectively. Use of licit and illicit substances was comparable to that of chronological peers and prior national studies of medical trainees. Most of the students admitted to using alcohol at least once in the prior year (91.8% and 95%, respectively). In both years marijuana was the illicit drug used most often. Although there was a slight increase over time in the use of benzodiazepines (2.4% to 5.8%) and a decrease in the use of marijuana (29.4% to 21.7%), these changes were not significant. Few of the students in their third year reported using any substance other than alcohol more than once a month. In general, a greater percentage of the students reported a decrease rather than an increase in the use of a substance since entering medical school; the primary exception was for wine. As they progressed in their training, the students became less concerned about the effect of substance use on their performance and more likely to be embarrassed about admitting to an addiction. Although in each year a few of the students appeared to be at risk for substance dependence (8.9% and 3.5%, respectively), no student came to the attention of the administration because of problems related to substance use. While most of the students were unaware of any classmate who had a problem, half of those who were aware had done nothing, and the balance had rarely sought assistance from the faculty or administration. CONCLUSION: Although there was no evidence that substance use was a major problem, a few of the students appeared to be at risk for drug or alcohol dependence. Appropriate intervention, support, and referral systems should be identified for the few who may be at risk, and increased educational efforts are needed to help all students address this issue with their peers and, ultimately, with their patients.     

Pituitary growth hormone release and gene expression in cafeteria-diet-induced obese rats

PURPOSE: To determine prospectively the feasibility and accuracy of combined gadolinium-enhanced magnetic resonance (MR) angiography, MR urography, and MR nephrography in the presurgical evaluation of potential renal transplant donors. MATERIALS AND METHODS: Twenty-two potential donors for renal transplantation were evaluated with 1.5-T MR imaging. MR angiograms were evaluated for the number of renal arteries, presence of early arterial branches, and renal artery stenoses. The renal collecting system and ureters were evaluated on the MR urograms. Renal parenchyma was assessed on the MR nephrogram. Prospective interpretation of MR images was compared with that of conventional angiograms and excretory urograms and with surgical findings. RESULTS: Gadolinium-enhanced MR angiography enabled correct identification of the arterial supply to all 44 native kidneys (44 single or dominant renal arteries and nine accessory renal arteries), four of five early arterial branches arising in the proximal 2 cm of the renal artery, a mild truncal stenosis in one renal artery, and two anomalies of the draining renal veins. The MR urogram accurately depicted a duplicated collecting system and mild unilateral pelvicalicectasis. The MR nephrogram showed renal size and a solitary cyst in one kidney, confirmed with sonography. CONCLUSION: Combined gadolinium-enhanced MR angiography, MR urography, and MR nephrography can accurately depict the arterial supply, collecting system, and renal parenchyma of donor kidneys.     

Enteric hyperoxaluria: dependence on small intestinal resection, colectomy, and steatorrhoea in chronic inflammatory bowel disease

The importance of intestinal resection, exclusion of the colon, and steatorrhoea for secondary hyperoxaluria was studied in 81 patients with Crohn's disease and 12 patients with ileostomy after colectomy for ulcerative colitis during a metabolic regime including a fixed oral supply of fat, calcium, and oxalate. Hyperoxaluria (greater than 48 mg (greater than 0.5 mmol) per 24 h) was present in 21 patients with Crohn's disease. All but one half or more of the colon preserved. Renal oxalate excretion was related to the amount of ileum resected. 14C-oxalate absorption was significantly higher in patients with ileal resection and the whole colon preserved than in patients with ileal resection plus hemicolectomy, despite the fact that the latter group had the most extensive ileal resections. Faecal fat and oxalate excretion agreed well in patients without ileostomy (r = 0.76, p less than 0.001), and renal oxalate excretion was significantly higher in patients with steatorrhea and the colon preserved than in patients without steatorrhoea. In all 93 patients 14C-oxalate absorption and renal oxalate excretion was positively correlated with a coefficient of correlation of 0.76 (p less than 0.001). No correlation was present between 47Ca- and 14C-oxalate absorption. The study confirm that a preserved colon is necessary for secondary hyperoxaluria and stresses the importance of ileal resection and steatorrhoea.     

The galanin antagonist, M-15, inhibits growth hormone release in rats

The neuropeptide, galanin, has been implicated in the regulation of rat growth hormone (rGH) release. In the present study, adult male rats were implanted dually with cannulae to the lateral cerebral ventricle and the right atrium. After surgical recovery, rats were infused with M-15, a specific galanin antagonist, into the lateral ventricle. During the course of this brain infusion, rats were subjected to serial blood sampling with red cell and artificial plasma replacement under stress-free conditions. Plasma was saved for rGH assay. Treatment with M-15 reduced rGH pulse amplitude and pulse frequency when compared to vehicle-infused controls. These data suggest that brain galanin participates in the ongoing stimulation of pulsatile rGH release in the adult male rat.     

Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice

In previous studies, we demonstrated that in ANG II-treated rats, prevention of cardiac hypertrophy (CH) by enalapril was blunted by bradykinin (BK) blockade by Hoe140. The putative role of BK was assessed by chronic exogenous BK infusion and in 46 male Sprague-Dawley rats infused with ANG II. ANG II (200 ng/kg/min) alone and associated with BK at low (BKlow, 15 ng/kg/day), mid (BKmid, 100 ng/kg/day) and high doses (BKhigh, 100 ng/kg/min) were delivered by Alzet osmotic pumps for 10 days and compared to control animals (Veh). Values of systolic arterial pressure (SAP, mmHg) in conscious rats and heart weight (HW, mg/g bw) at the end of the study are reported below. Results were submitted to ANOVA and are expressed as mean +/- SEM.     

Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs

OBJECTIVE: A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH-secreting and non-functioning pituitary adenomas. SUBJECTS AND METHODS: Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non-functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty-five patients were treated for 1 month with octreotide (300 micrograms daily). The therapeutic response was assessed on GH and IGF-I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied. RESULTS: From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide-induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non-functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non-functioning pituitary adenomas with expression of sst2 only. CONCLUSION: In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.     

The effect of malnutrition during the early period of postnatal ontogenesis on the amylolytic and invertase activity of the small intestinal mucous membrane of growing rats

Acute experiments demonstrated that undernourishment caused during the first half of the lactation period of development (8 days of life) by keeping 16 young ones per each lactating female-rat or by 16-hour long weaning of rattlings from their mothers results in a drastic reduction of both specific amylolytic and invertase activity in different sections of the small intestine and in that of the latter's weight. This phenomenon becomes apparent not only at the time of undernourishment, but also during a fairly long period following putting the animals on an ordinary dietary regimen.     

Overnight urinary growth hormone in normally growing prepubertal children: effect of urine volume. The one-year growth study

Wear of the polyethylene tibial components is a potential cause of failure in total knee arthroplasty. In addition to pitting, burnishing, and scratching, subtle striations on the bearing portion of the tibial surface have been observed in components retrieved relatively early after implantation. The striated pattern most typically occurred in areas centrally located within the articulating surface. The striations were anteroposterior directed and were identified as local cold flow at the surface. There was a strong correlation between the medial and lateral striated areas, suggesting that these patterns are related to cyclic rolling of the knee. The general characteristics and alignment of the striations could be attributed to the compressive and tractive forces occurring during femoral rollback. For the clinician, these results suggest that kinematics, as well as contact stress, should be considered when evaluating wear of polyethylene components.     

Preventive administration of ornithine alpha-ketoglutarate improves intestinal mucosal repair after transient ischemia in rats

Introduction; Healthcare professionals need to continually update their knowledge to provide care based on scientific evidence. In some cases it can be difficult to gain access to the different sources of medical information. In an attempt to overcome these problems, a toll-free telephone medical information service (Doctorline) was established. OBJECTIVE: To describe the development, aims, organization, and activities of this private service. METHODS: Doctorline is an independent, unbiased, toll-free medical information service that provides information on clinical, pharmacologic, and toxicologic issues; bibliographic searches; full-text articles; public and private clinics; details of forthcoming congresses; and legislative documentation. The service is available Monday through Friday, 1000 to 2000. Staff members are physicians trained in communication techniques, literature evaluation methodologies, and computerized database use. The main on-line facilities are MEDLINE, Micromedex-CCIS, and the Italian Formulary on CD-ROM. Books, bulletins, national and international drug formularies, and property files (i.e., directory of Italian public and private clinics) are also available. RESULTS: In 5 years, Doctorline has received 65 258 calls. Nearly 34% of the calls were made by general practitioners, followed by cardiologists (22%), orthopedists (15%), pharmacists (14%), gastroenterologists (13%), and urologists (10%). From 1991 to 1996, nearly 20% of the calls concerned pharmacologic issues, 43% nonpharmacologic issues, while the rest of the calls were for nonclinical requests. Approximately 21% of all questions received an answer during the same phone call (on-line answers); for the other answers (off-line answers) the mean +/- SD waiting time was 7.8 +/- 10.4 days. Although the nature of the questions has been recorded since 1991, data about the exact number of physicians who used the service are available only from 1994. Data from 1994 indicate that of the 52,181 physicians who could access the service, only 8817 (16.9%) called at least once, with a mean number of calls per physician of 3.9 (range 3.0-5.6). CONCLUSIONS: The future of Doctorline will depend on the quality and validity of the information provided (i.e., based exclusively on scientific evidence, independent of the source of funds), the promotion of the aims, organization, and clinical utility of the service (especially among physicians who made little or no use of the service), and differentiation of the service activities in relation to the physician's specific needs.     

Growth hormone and insulinlike growth factor 1 promote intestinal uptake and hepatic release of glutamine in sepsis

The aim of the present study was to establish whether the steroids, progesterone, androstenedione, testosterone and oestradiol, were present in the mesonephric-gonadal complex of female and male sheep fetuses around sexual differentiation (that is, from day 28 to day 45 of gestation, with sexual differentiation occurring at approximately day 32). A second aim was to test whether the mesonephric-gonadal complex, mesonephros (days 35-45 only) and gonad (days 35-45 only) were capable of steroid synthesis in vitro. The steroid contents in the mesonephric-gonadal complex were not detectable before sexual differentiation. However, from day 35 of gestation onwards, the mesonephric-ovarian complex contained mainly oestradiol and the mesonephric-testicular complex contained mainly testosterone: from day 35 until day 45 the increase in content of these two steroids exceeded the increase in the mass of tissue by more than fivefold. From day 40 to day 45 of gestation, the contents of the other steroids in the pathways to oestradiol increased progressively in both sexes but more in parallel with the increase in tissue mass. In contrast to the steroid contents in the tissue at recovery, the mesonephric-gonadal tissue from both sexes in tissue culture was able to synthesize most steroids before and after sexual differentiation and also to metabolise supplementary androstenedione to oestradiol. These findings suggest that many, if not all, of the steroidogenic enzymes in the pathway from cholesterol to oestradiol are present before sexual differentiation. Most of the aforementioned steroids were present in detectable amounts in isolated mesonephros and gonad of both sexes after sexual differentiation. Moreover, for both the isolated mesonephros and gonad, there were increases in the mean contents of most steroids after culture relative to the contents in the tissues at recovery. These data suggest that the mesonephros, as well as the gonad, in both sexes is capable of synthesizing steroid. It is concluded that, in the sheep fetus, the female and male gonads are steroidogenically active after sexual differentiation, that the steroidogenic enzymes develop before sexual differentiation, and that the mesonephros is a site of steroid synthesis.     

The role of growth hormone, somatostatin and glucagon in hepatic resection

BACKGROUND/AIMS: The aim of this study was to clarify the roles of growth hormone, somatostatin, and glucagon in vital reactions against surgical stress as well as in hepatic regeneration. METHODOLOGY: Eleven consecutive patients, who underwent hepatic resection, were included in this study. Changes in intrinsic hormones, specifically growth hormone, somatostatin, and glucagon, were investigated. Furthermore, a comparison was made between major (more than 2 segments) and minor (less than 1 segment) hepatectomies. RESULTS: Growth hormone was observed to increase four-fold during hepatectomy and thereafter remained at relatively high levels. Somatostatin reached its lowest level on postoperative day 1 and then returned to near the preoperative level on postoperative day 7, while glucagon gradually increased and reached a peak around postoperative day 3. The concentrations of both somatostatin and glucagon in the portal vein were higher than those in the peripheral vein. No significant differences between major and minor hepatectomies were found throughout the perioperative course. CONCLUSIONS: Growth hormone is considered to be a sensitive parameter in terms of surgical stress and can also act as a trigger as well as a promoter of hepatic regeneration, while a dissociation between somatostatin and glucagon in the early postoperative period indicates the promotion of hepatic regeneration. Furthermore, portal blood, which contains higher concentrations of these substances, plays an important role in regulating hepatic regeneration. However, the absence of a correlation between the extent of the hepatectomy and these parameters suggests that some other, as yet unidentified mechanism, may also be related to the regulation of hepatic regeneration.     

The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes

The type 1 copper in Pseudomonas aeruginosa azurin was studied by electron paramagnetic resonance (EPR) spectroscopy at low microwave frequencies. Partially resolved ligand hyperfine structure was observed in the perpendicular region of the spectra at both S-band (2.4 GHz) and L-band (1.1 GHz). A trial and error method, requiring several hundred simulations, has been used to simulate the low frequency EPR data and yield an optimum value of 30 MHz for ACUx, more than one half that previously reported. The fit between the simulated and experimental data is sensitive to changes in the Euler angles and, in particular, to the angle alpha which rotates the Cu A-tensor about the z-axis. Thus, the A- and g-tensors for copper in P. aeruginosa azurin do not appear to be coincident. A value for the Euler angle beta of at least 10 degrees does not disturb the fit between the simulated and experimental data. These studies demonstrate the advantage of evaluating EPR parameters from simulations at more than one frequency, especially at low frequencies where ligand superhyperfine structure may be resolved for type 1 copper.     

Angiotensinergic neurons physiologically inhibit prolactin, growth hormone, and thyroid-stimulating hormone, but not adrenocorticoptropic hormone, release in ovariectomized rats

Angiotensin II (AII)-containing neurons with cell bodies in the rostral medial hypothalamus and axons project to the external layer of the median eminence, so that AII maybe released into the hypophyseal portal vessels for actions on the pituitary gland. Indeed, intrahypothalamic actions of the peptide on the release of hypothalamic hormones and direct actions on the pituitary have been reported. To determine the role of endogenously released AII in hypothalamic-pituitary hormone release, we have determined the effects of central immunoneutralization of AII upon the plasma concentrations of prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH). Specific antiserum directed against AII (AB-AII) or normal rabbit serum (NRS), as a control, was microinjected into third ventricular (3 V) cannulae of conscious, ovariectomized (OVX) rats. Immediately before and at various intervals after this procedure, blood samples were withdrawn through previously implanted external jugular catheters. Three hours after injection of the AB-AII, plasma PRL levels diverged from those of the NRS-injected animals and progressively increased from 4 to 24 h after administration of the antiserum. Results were similar with respect to plasma GH, except that the increase in the AB-AII animals above that in the NRS-injected controls from 4 to 6 h was not significant, but was highly significant on measurement 24 h after injection, at which time plasma GH was three times higher than in control rats. Similarly, following injection of AB-AII, plasma TSH values did not diverge significantly from those of the NRS-injected controls until 3 h after injection. From 3 to 5 h they remained constant and significantly elevated above values in the NRS-injected controls with a further nonsignificant increase at 6 h. At 24 h, there was no longer a difference between the values in both groups. In contrast to the significant elevations in plasma hormone levels observed with respect to PRL, GH, and TSH following injection of the antiserum, there was no change in plasma ACTH between the AB-AII-injected and NRS-injected animals throughout the same period of observation. Previous results by others have shown that intraventricular injection of AII has a suppressive action on the release of PRL, GH, and TSH. Consequently, we believe that the antiserum is acting intrahypothalamically to block the action of AII within the hypothalamus, resulting in the elevation of the three hormones mentioned. Therefore, the AII neurons appear to have a physiologically significant suppressive action on the release of hypothalamic neurohormones controlling the release of PRL, GH, and TSH. In contrast, there apparently is no effect of intrahypothalamically released AII on the secretion of corticotropin-releasing factors under these nonstress conditions. We cannot rule out an action of the antiserum at the pituitary level; however, in view of the fact that the actions of AII directly on the gland are to stimulate PRL, GH, TSH, and ACTH release, it appears that the antiserum was acting at the hypothalamic level.