Intervals Blood Samples Research Articles

The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial.

PurposeElevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes.MethodsIn a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5–10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen.ResultsWP reduced PPG area under the curve [AUC0–60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects.ConclusionPre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual’s insulin resistance, their obese state, or other obesity-related ailments needs further investigation.Clinical Trial RegistrationISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.

Evaluation of postpartum metabolic and health response in dairy cows with different body condition score during the dry period

This study aimed to evaluate the effects of different pre-calving body conditions on some metabolic indices, health status and reproductive disorders in dairy cows. The study was conducted on a dairy farm in Eastern Slovakia during the pre-partum period (–1 to –10 DIM) and post-partum period (1 to 14 DIM). Total of 84 cows allotted in 3 groups were submitted to clinical examination and body condition score (BCS) evaluation. At the same intervals blood samples were collected for determination of beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), and calcium levels. During the postpartum period the incidence of reproductive diseases, such as metritis, retained placenta, metabolic disorders, such as milk fever, left displacement of abomasum and orthopaedic disorders were recorded. The strongest lipid mobilisation (NEFA elevation), ketone body production, and blood calcium drop were determined in postpartum dairy cows with the highest prepartum body condition score. In conclusion, the dairy cows with different BCS hade a different metabolic response during the postpartum period. The overcondition was connected with stronger lipid mobilisation and calcium drop after calving. Moreover, the higher BCS could contribute to higher incidence of production diseases.

2276-PUB: A Palatable, Novel Whey Protein Shot Attenuates Postprandial Glycemia in Lean and Centrally Obese Adult Males

Background: Consuming large doses of whey protein (WP) ∼30 minutes before high-glycemic load meals reduces postprandial glycemia (PPG). However, it is unclear if this effect is retained at smaller doses of WP, ingested at realistic times before typical meals. Moreover, as central obesity is associated with elevated PPG, WP may offer benefit in improving PPG within such individuals. We examined the PPG responses to breakfast following consumption of a small WP shot in centrally obese and lean males. Methods: In a randomized-crossover design, 7 lean (BMI 24.3±1.5; waist circumference 79.3±7.1 cm; waist/hip ratio [WHR] 0.83±0.04) and 9 centrally obese (34.6±1.9; 112.8±10.2 cm; 0.97±0.1) age-matched, adult males performed two 240 minutes mixed-meal tests, 7d apart. After an overnight fast, participants consumed either a 100ml ready-to-drink WP shot (15g Protein) or 100ml water (CON) 10 minutes before a typical breakfast meal. Interval blood samples were collected for the measurement of plasma glucose. Data (mean±SD) were analyzed by a mixed-design ANOVA and Pearson’s correlation with significance accepted as p≤0.05. Results: WP reduced early PPG AUC0-60min by 22±9.3% and 13.1±10% in lean and obese males, respectively, vs. CON (p&amp;lt;0.01). Obese males had greater AUC0-60min following WP vs. lean (p=0.02) with no differences after CON (p=0.62). Total trial glucose AUC0-240min was comparable between conditions in both groups (p&amp;gt;0.05). WP reduced peak PPG vs. CON (lean: -26.5±7% [p&amp;lt;0.001]; obese: -16.4±9.8% [p&amp;lt;0.01]) with a tendency for more marked reductions within lean males (p=0.052). Central obesity (WHR) was associated with greater increases in glucose from fasting values, despite WP consumption (r=0.7; p&amp;lt;0.01). Conclusion: Consuming a palatable, ready-to-drink WP shot before breakfast attenuates early elevations in PPG and reduces hyperglycemia in lean and centrally obese males. Central obesity predicts the glucose lowering effect of WP and may limit its application in this group. Disclosure K. Smith: None. G.S. Taylor: None. N. Okwose: None. D.M. Allerton: None. L.H. Brunsgaard: Employee; Self; Arla Foods Ingredients. E.J. Stevenson: None. D.J. West: Research Support; Self; Arla Foods Ingredients, Dexcom, Inc. Funding Arla Foods Ingredients Group P/S

The Use of Allogenic Stromal Vascular Fraction (SVF) Cells in Degenerative Joint Disease of the Spine in Dogs.

Stem cells are widely used in regenerative medicine and in clinical practice for the treatment of damaged nerve tissue, myocytes, tendons, and ligaments. The aim of the study was to monitor VEGF levels after the administration of allogenic cellular material (SVF) in the course of treatment of dogs suffering from degenerative joint disease in the spinal region. The study was conducted on 10 dogs of both genders, aged between 6 and 13 years in which allogenic stromal vascular fraction of stem cells (SVF) was administered intravenously. The control group was composed of 10 clinically healthy dogs. Before treatment and after 2- and 8-week intervals blood samples were obtained from the study group dogs in order to determine VEGF levels via immunoenzymatic test. in a few days after the therapy, alleviation of pain symptoms and reduction of lameness were noticed. The VEGF level in 2 weeks after the therapy was significantly elevated (median: 38.77 pg/ml), while in 8 weeks a decrease was observed (median: 18.37 pg/ml). Conlusion: Administration of allogenic stem cells has a positive influence on elevation of the VEGF levels in the blood serum of affected animals as well as their regeneration capacity.

Effect of Peripheral Administration of Kisspeptin-10 on Dynamic LH Secretion in Prepubertal Ewes.

The aim of the present study was to clarify the effect of kisspeptin-10 on LH secretion in prepubertal ewes. In experiment 1, prepubertal ewes fitted with indwelling jugular catheters were randomly assigned to receive 0, 0.5, 1 or 2 mg of kisspeptin-10 dissolved in saline, and serial blood samples were collected at 15-min intervals for 180 min to analyze the response curves of LH after injection. In experiment 2, prepubertal ewes fitted with indwelling jugular catheters were injected with 0 or 1 mg of kisspeptin-10 dissolved in saline and the injection was repeated 3 times at 1 h interval and serial blood samples were collected at 15-min intervals for 210 min to analyze the response curves of LH after injection. The results showed that single intravenous administration of 0.5, 1 and 2 mg of kisspeptin-10 all could significantly increased LH secretion in prepubertal ewes, and the effect of 1 and 2 mg of kisspeptin-10 on LH secretion was higher than that of 0.5 mg group. The results also showed that repeated intravenous administration of kisspeptin-10 could effectively increase LH secretion and repeated administration did not influence the effect of kisspeptin-10 on LH secretion in prepubertal ewe. In conclusion, the present study indicated that single or repeated intravenous administration of kisspeptin-10 could effectively increase LH secretion in prepubertal ewes.

&lt;i&gt;In vivo&lt;/i&gt; pharmacokinetic studies of prodrugs of ibuprofen

In vivo pharmacokinetic studies of N-Mannich base derivatives of ibuprofenamide as prodrugs were performed on rabbits. Ibuprofen and both the prodrugs (IBMB-M and IBMB-P) were administered orally and at different time intervals blood samples were collected and assayed for ibuprofen and ibuprofenamide by HPLC method. From the plasma concentration-time profile; (C p ) max , t max , AUC and the time required to achieve minimum effective concentration were calculated. N-Mannich base prodrugs first get hydrolyzed to ibuprofenamide which in turn gets hydrolyzed to ibuprofen by the enzyme amidase. The (C p ) max and AUC values of IBMB-M were found to be more compared to IBMB-P. In both the cases ibuprofen started appearing after 2 h and it required minimum 4 h to get the ibuprofen in therapeutic range. Both the prodrugs released ibuprofen slowly which gave sustained effect. IBMB-M provided ibuprofen in therapeutic range for 48 h and IBMB-P for 24 h.

Effect of triglycerides with different fatty acid chain length on superior mesenteric artery blood flow

Fat stimulates superior mesenteric artery (SMA) blood flow. Little is known, however, about the influence of fatty acid chain length on SMA flow. The present study was performed to compare the effect of long chain triglycerides (LCT, corn oil), very long chain triglycerides (VLCT, fish oil) and medium chain triglycerides (MCT) on SMA flow. A total of seven healthy volunteers (four men, three women; aged 26 +/- 4 years) participated in three experiments, performed in random order during 60 min continuous intra-duodenal infusion of either LCT (30 mL h(-1); 240 kcal h-1), equicaloric VLCT (30 mL h(-1); 240 kcal h(-1)) or MCT in equimolar (15 mL h(-1); 113 kcal h(-1)) and equicaloric amount (30 mL h(-1); 225 kcal h(-1)). Basal and stimulated SMA blood flow were measured by Doppler ultrasonography. At regular intervals blood samples were taken for measurement of plasma cholecystokinin (CCK) and plasma peptide YY (PYY). Basal SMA blood flow volumes were not significantly different among the LCT, VLCT and MCT experiments (426 +/- 135, 460 +/- 114 and 503 +/- 177 mL min(-1), respectively). The SMA flow increased significantly (P < 0.05) during fat infusion but was significantly higher during LCT (1460 +/- 692 mL min-1) compared with VLCT (1061 +/- 384 mL min-1), MCT 15 mL h(-1) (870 +/- 286 mL min(-1)) and MCT 30 mL h-1 (904 +/- 223 mL min(-1)). Plasma CCK levels increased significantly (P < 0.05) during LCT and VLCT but not during MCT infusion. No correlation was found between SMA flow and plasma CCK levels (r = 0.27; P = 0.2) The SMA blood flow in response to triglycerides is dependent on fatty acid chain length. This chain length-dependent blood flow response is, however, not linear and is not related to plasma CCK levels.

Mixed venous oxygen saturation and biochemical parameters of hypoxia during progressive hypoxemia in 10- to 14-day-old piglets.

In this study we wanted to assess the relationship between mixed venous oxygen saturation (SVO2) and tissue oxygenation. For that, we compared the values of SVO2 with oxygen delivery (DO2), oxygen consumption (VO2), and markers of tissue hypoxia such as lactate and pyruvate during progressive hypoxemia. Eight 10-14-d-old piglets were anesthetized, tracheotomized, intubated, and ventilated. A fiberoptic catheter was placed in the carotid artery to monitor arterial oxygen saturation (SaO2). A thoracotomy was performed, and a fiberoptic catheter was placed in the pulmonary artery to monitor SVO2. A transit time ultrasound flow probe was positioned around the ascending aorta to measure aorta flow. Progressive graded hypoxemia was induced by decreasing fractional inspiratory oxygen concentration (FIO2) from 1.0 to 0.30, 0.21, 0.15, and 0.10. After each FIO2 interval blood samples were taken for blood gases, lactate, and pyruvate. DO2 and VO2 were calculated. SVO2 decreased similarly to SaO2. A value of SVO2 of more than 40% excluded oxygen restricted metabolism. When DO2 decreased below a critical range (8.4-12.8 mL/kg x min), SVO2 decreased below 15%, and lactate and the lactate/pyruvate ratio increased. We conclude 1) that baseline SVO2 values excluded oxygen-restricted metabolism, 2) that SVO2 values between 15 and 40% were not a marker for oxygen-restricted metabolism, and 3) that SVO2 values below 15% were associated with oxygen-restricted metabolism. Reduced SVO2 values must be interpreted as a change of the factors that determine the balance between DO2 and VO2 and as a warning that, with further reduction of SVO2, oxygen restricted metabolism can develop.

Substrate mobilization and hormonal changes in rainbow trout (Oncorhynchus mykiss, L.) and common carp (Cyprinus carpio, L.) during deep hypoxia and subsequent recovery

Common carp (at 20°C) and rainbow trout (at 15°C) were fitted with an indwelling cannula in the dorsal aorta. The fish were exposed to a controlled decline of waterpO2 followed by 90 min deep hypoxia at 0.3 kPa (carp) or 4.8 kPa (trout). Thereafter, normoxic recovery was monitored in both species for 48 h. At regular intervals blood samples were analysed for glucose, lactate, free fatty acids, adrenaline, noradrenaline and cortisol. The oxygen restriction was maximal in both species and resulted in a significant increase of plasma lactate levels. In carp, adrenaline, noradrenaline and cortisol levels increased to 2, 50, and 753 ng·ml-1 respectively during anoxia, whereas in trout these hormones increased to 12, 8 and 735 ng·ml-1 respectively during hypoxia. In hypoxic trout, the plasma levels of glucose (3 mol·l-1) were increased modestly whereas levels of free fatty acids (0.25 mmol·l-1) were decreased to 0.15 mmol·l-1. In carp, however, a marked and prolonged hyperglycaemia (from 5 to 10 mmol·l-1) and a significant continuous depression of plasma levels of free fatty acids (from 0.4 to 0.2 mmol·l-1) were observed indicating a difference in metabolic organization. It is suggested that hyperglycaemia is likely to be the result of hepatic glycogenolysis, stimulated by circulating catecholamines and a stimulation of gluconeogenesis by cortisol during recovery. The mechanism for the decline of plasma levels of free fatty acids is most probably a reduction of lipolytic activity, which appears to be an adaptation to hypoxia.

Influence of direction of body weight change on pattern of gonadotropin secretion in ovariectomized beef heifers of equivalent body weight.

Our hypothesis was that alterations in pattern of gonadotropin secretion induced by level of dietary energy intake are dependent on direction of BW change. Beef heifers were assigned to one of two treatments 21 d after ovariectomy: 1) increasing followed by decreasing BW (I-D; n = 9) or 2) decreasing followed by increasing BW (D-I; n = 9). Heifers assigned to the I-D treatment received 15.4 Mcal ME/d (HE) from wk 0 to 8 followed by 4.3 Mcal ME/d (LE) from wk 9 to 16. Heifers assigned to the D-I treatment received the LE diet for the initial 8 wk followed by the HE diet for the subsequent 8 wk. At 2-wk intervals blood samples were collected at 10-min intervals for 11 h to determine the pattern of secretion and(or) concentration of gonadotropins in circulation (LH and FSH) and pituitary responsiveness to administration of 750 ng and 50 micrograms of LHRH. Frequency of LH pulses increased (P less than .05) in a quadratic fashion with increasing ADG in heifers in both treatment groups. Amplitude of LH pulses decreased (P less than .05) in a linear fashion with increasing ADG in heifers in both treatment groups and magnitude of this decline was greater (P less than .05) in heifers receiving the D-I treatment. Amplitude of response to 750 ng of LHRH decreased (P less than .05) in a linear fashion with increasing ADG in heifers receiving the D-I treatment but was unrelated to changes in ADG (P greater than .05) in heifers receiving the I-D treatment. When heifers in both treatment groups attained similar BW (P greater than .05; wk 14), amplitude of LH pulses, responsiveness to 750 ng of LHRH and mean concentration of FSH in serum were higher (P less than .05) in heifers receiving the I-D than in heifers receiving the D-I treatment. Thus, we accept the hypothesis that alterations in pattern of gonadotropin secretion in heifers fed diets with a low energy content are dependent on direction of BW change.

Radiation Nephropathy in Mature Pigs Following the Irradiation of Both Kidneys

Both kidneys in mature female Large White pigs, ca. 45 weeks old were irradiated with single doses of 7.8-14.0 Gy of 60Co gamma-rays. Radiation-induced changes in renal function were assessed on the basis of sequential individual measurements of kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) for up to 24 weeks after irradiation. At the same time intervals blood samples were taken to determine plasma renin levels and the haematological status of each animal. Two weeks after irradiation the ERPF and in particular the GFR was increased. This was followed by a pronounced, dose-dependent, decline in renal haemodynamics. Minimal functional levels were observed 8-12 weeks after irradiation. Function then somewhat recovered. There was a significant (r greater than or equal to 0.98; p less than 0.001) inverse relationship between the mean values of GFR and ERPF, determined at 4-24 weeks after irradiation, and the radiation dose. After a dose of 7.8 Gy the reduction in ERPF was greater than that for GFR. However, at higher doses both parameters were reduced to an equal extent. The resulting slope of the dose-effect curve for impaired renal function versus dose was significantly steeper for GFR than that for ERPF (p less than 0.001). There was a significant reduction (p less than 0.002) in the erythrocyte count, the haematocrit and haemoglobin levels within 6-8 weeks of irradiation; this anaemia was characterized as a normochromic normocytic anaemia. There were no marked changes in plasma renin levels as a result of renal irradiation. The pathogenesis of late radiation-induced damage to the kidney is discussed in the light of these findings.

Ionized calcium in monitoring effective parathyroidectomy: a preliminary report.

AbstractThis study set out to determine the validity of a laboratory technique that might provide the surgeon with an indication of effective parathyroidectomy before the patient leaves the operating room. Seventeen patients with a firm diagnosis of primary hyperparathyroidism established by conventional criteria (11 adenoma and 6 hyperplasia) came to operative treatment. During operation, interval blood sampling was carried out for duplicate determination of ionized calcium using the Radiometer ICA 1 Analyzer, which also measures pH and corrects ionized calcium to a pH of 7.4. Samples, usually 6 in number or more, were collected about every 20 minutes throughout operation. The times of parathyroid sampling or excision were noted and correlated with ionized calcium levels.Twelve of the 17 patients showed a marked decline in ionized calcium levels 40–120 minutes following presumptive effective parathyroidectomy. If measured on site, these results would have been available before the patient's departure from the operating room. All these patients achieved eucalcemia. In 5 patients, there was no significant decline in ionized calcium. Four of these patients became eucalcemic, the fifth patient showed a marked decrease in total serum calcium, but not to normal levels. Three control patients showed no evidence of alteration in ionized calcium.This study should be construed as preliminary, but does provide a basis for continued investigation. While it is apparent that a lack of decline of intraoperative ionized calcium does not exclude cure, the occurrence of such a decline provides strong evidence of curative parathyroidectomy. This technique, if confirmed by further work, permits a rapid, reliable, simple measure which would be available to most hospitals.

The effect of androgen blockade on pulsatile gonadotrophin release and LH response to naloxone.

In order to clarify the effects of androgen blockade on the hypothalamic-pituitary-testicular axis in man, four patients with advanced prostate cancer, not previously treated, were given oral flutamide, 250 mg three times daily for 9 days. Before, and 7, 8 and 9 days after starting flutamide treatment, on separate days, the following tests were performed: a gonadotrophin pulsatility study, with 20 min interval blood sampling for 12 h, a naloxone test and a GnRH test. Flutamide induced a significant increase in both LH and FSH pulse frequency, while pulse amplitudes and plasma integrated concentrations (IC) of LH and FSH were unaffected. Plasma integrated concentrations of testosterone and oestradiol rose significantly, while that of prolactin was unaffected. The increase in plasma LH concentration induced by naloxone injection was abolished by flutamide treatment. On the other hand, the small FSH response to naloxone was unaffected by flutamide treatment. Response to GnRH was unaffected by flutamide. These results suggest that flutamide exerts effective androgen blockade at the hypothalamic level, since, despite increased plasma testosterone concentrations, gonadotrophin pulse frequency increased and the LH response to naloxone was abolished.

Preoptic catecholamine, GABA, and glutamate release in ovariectomized and ovariectomized estrogen-primed rats utilizing a push-pull cannula technique.

The push-pull cannula technique was used to evaluate the role of the medial preoptic/anterior hypothalamic area (MPO) in regulating pituitary luteinizing hormone (LH) and prolactin release. The concentrations of the three catecholamines--dopamine, norepinephrine (NE), epinephrine (E)--and gamma-aminobutyric acid (GABA) and glutamate could be measured in 15-min fractions at which interval blood samples for LH and prolactin determination were also collected. Comparison of neurotransmitter release rates into the MPO were made between ovariectomized and ovariectomized estradiol benzoate treated rats. Release of the neurotransmitters occurred in a pulsatile manner, the release episodes for each transmitter appeared to be independent of the others. No direct correlation between neurotransmitter release episodes and blood LH or prolactin levels could be established. The release of GABA was significantly lower and that of NE and E higher in ovariectomized animals in comparison to estrogen-primed ovariectomized animals under negative feedback conditions. In the afternoon, however, when the estrogen stimulated LH and prolactin release, preoptic GABA release was low, whereas preoptic NE and particularly E release rates were high. Conspicuously high dopamine and NE release episodes were observed in estrogen-primed animals at noon, i.e., prior to the expression of the positive feedback signal. This may reflect a biochemical correlate to the so-called critical period. No consistent differences between ovariectomized and ovariectomized estradiol-17 beta benzoate treated animals were observed for preoptic glutamate release rates. The data show that preoptic GABA release rates show generally an inverse pattern to NE and E release and therefore also to blood LH and prolactin levels. No direct mathematical correlation between any of the neurotransmitter release rates and blood hormone levels could be established.

Infusion of cholecystokinin octapeptide in man: relation between plasma cholecystokinin concentrations and gallbladder emptying rates.

To establish the sensitivity of the gallbladder in relation to plasma concentrations of cholecystokinin, a dose-response study was performed in five normal volunteers. Cholecystokinin octapeptide was infused in ascending incremental dose sequence, interval blood samples taken for estimation of plasma hormone concentrations and gallbladder emptying rates monitored continuously using 99mTc-HIDA. In five other volunteers, gallbladder emptying rates following a liquid fat meal were measured. Infusion rates of 0.0, 0.75 +/- 0.2, 6.8 +/- 0.5, 23.8 +/- 1.6 and 66.1 +/- 2.5 pmol cholecystokinin kg-1 h-1 produced plasma concentrations of less than 3.0 (undetectable), less than 3.0, 6.6 +/- 1.8, 13.3 +/- 1.5 and 26.9 +/- 2.9 pmol l-1 respectively and gallbladder emptying rates (% min-1) of 0.0, 0.0, 0.14 +/- 0.15, 1.57 +/- 0.38 and 4.29 +/- 1.12. Following the fat meal, peak plasma cholecystokinin concentrations reach 30 pmol l-1 and gallbladder emptying rates (% min-1) are 3.86 +/- 1.01. We conclude that the threshold of the gallbladder to circulating cholecystokinin octapeptide is around 6 pmol l-1, but that infusions which result in plasma levels of around 25 pmol l-1 produce gallbladder emptying rates comparable with those seen after oral fat. This suggests that the gallbladder is equally sensitive to endogenous and exogenous cholecystokinin and that plasma concentrations observed after oral fat can entirely account for the gallbladder response.

Adrenal-gonadal function in rats with frontal hypothalamic transections.

All neural connections entering the hypothalamus from the anterior direction were severed by means of a Halász knife-cut in female rats at 22 days of age. The rats were then examined for vaginal opening and ovulation. At intervals blood samples were collected by cardiac puncture for the measurement of serum corticosterone (B). Unoperated rats showed vaginal opening at 36.5 +/- 2.1 days and ovulation within 2 days. A significant difference was found between B at 08.00 h and 18.00 h at the first sample interval chosen (28 days of age) and thereafter. Animals given sham surgery showed vaginal opening late (44.2 +/- 3.2 days, p smaller than 0.05) but ovulated within 2 days. These animals also had a significant 08.00-18.00 difference in B from day 28 on. Rats with frontal cuts in front of the suprachiasmatic nucleus (SCN) showed precocious vaginal opening (27.2 +/- 2.3 days, p smaller than 0.05) and early ovulation (28.2 +/- 0.7 days). A 08.00-18.00 difference was noted at 28 days of age but was lost after ovariectomy at 47 days of age. Implantation of a silastic estradiol benzoate capsule restored the 08.00-18.00 difference (p smaller than 0.01). Animals with cuts behind the optic chiasm (posterior frontal cuts) all showed early vaginal opening; some rats then ovulated (at 42.3 +/- 3.8 days) while others did not. No difference could be detected in the position of the cuts although there appeared to be more damage to the region just behind the SCN in the latter group. No 08.00-18.00 difference in B was found in the nonovulatory group and no difference was found in the ovulatory group until 44 days of age. It can be concluded that an isolated hypothalamic island containing the SCN will generate signals sufficient for precocious ovulation although subsequent ovulatory cycles are not regular.