Simultaneous circadian variations of plasma ACTH, beta-lipotropin, beta-endorphin and cortisol

The major objective of this study was to investigate the analogy existing between the typical circadian periodicity of ACTH and that recently described of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) plasma levels. The determination of their concentrations, plus cortisol, has been performed on the same plasma samples of 6 healthy volunteers. All hormones were measured by radioimmunoassay. Those of beta-LPH and beta-EP were preceded by a purification of plasma through silicic acid extraction and Sephadex G-75 gel filtration. The highest values (mean +/- SEM) were found in the morning (ACTH: 10.3 +/- 0.9; beta-LPH; 6.3 +/- 0.7; beta-EP: 6.5 +/- 0.5 fmol/ml; cortisol: 378 +/- 30 pmol/ml) and the lowest values in the evening (ACTH: 6:1 +/- 0.7; beta-LPH: 3.3 +/- 0.4; beta-EP: 3.7 +/- 0.6 fmol/ml; cortisol: 130 +/- 23 pmol/ml). Statistical analysis using the Fourier method led to the evidence of a concomitant circadian secretory pattern of the three proopiocortin-related peptides. These results strongly suggest that the phasic secretion of ACTH, beta-LPH and beta-EP underlies a common central control.     

Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.     

Beta-endorphin/beta-lipotropin release and gonadotropin secretion after acute exercise in normal males

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response to acute exercise and the relationship of these opioid peptides to basal and luteinizing hormone-releasing hormone (LRH)-stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion was studied in eight normal male volunteers. Acute exercise resulted in a rise in plasma beta-LPH levels that returned to base line when measured 60 min after exercise. Plasma beta-EP levels did not demonstrate any rise when measured immediately after 20 min of exercise or at 60 min after exercise. Serum LH concentrations in individual volunteers declined to nadir values 60-180 min after exercise after which they showed a rebound to levels higher than the preexercise values in three of five volunteers in whom nadir LH levels were attained before the final (180 min) measurement. Serum FSH concentrations were unaltered by exercise. Acute exercise similarly did not alter the LH/FSH response to exogenous LRH stimulation. Pretreatment of the volunteers with the narcotic antagonist, naloxone, failed to alter the postexercise or LRH-stimulated LH and FSH release. The data suggest that beta-EP does not exert a suppressive effect on LH secretion after acute exercise in normal human males. Whether the suppression of LH secretion after acute exercise in unconditioned males is due to factor(s) cosecreted with beta-LPH, an increase in brain beta-EP or to alternate mechanisms such as alteration in central dopaminergic or GABAergic tone remains to be established.     

Beta-endorphin/beta-lipotropin release and gonadotropin secretion after acute exercise in physically conditioned males

beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) concentrations were measured in the basal state and after acute exercise for 15 min or until exhaustion in 6 physically conditioned male volunteers. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and prolactin were also measured in the basal state. In addition, the concentrations of the gonadotropins (LH and FSH) were determined after exercise and the gonadotropin response to gonadotropin releasing hormone was assessed before and after exercise. The data show that acute exercise stimulates the release of both beta-EP and beta-LPH which return to base-line levels within 60 min after exercise. This is in contrast to our previously described results in physically unconditioned male volunteers in whom only beta-LPH release was noted after exercise. Serum LH concentrations declined after exercise reaching nadir values between 60 to 150 min after exercise. As we previously reported in physically unconditioned male volunteers, serum FSH concentrations did not change with exercise and the gonadotropin response to LRH stimulation was uninfluenced by exercise. Serum testosterone and prolactin concentration were within the normal range for healthy adult males. We speculate that the difference in beta-EP release with exercise in physically conditioned and unconditioned males represents a difference in processing of the opioid precursor molecule (pro-opiomelanocortin, POMC) in the two groups.     

Stress-induced changes in plasma concentrations of immunoreactive beta-endorphin and cortisol in response to routine surgical procedures in lambs

Following four different surgical procedures in lambs 3-5 weeks old, plasma immunoreactive beta-endorphin (beta-EP) and cortisol were assayed at 15 min and 24 h as determinants of post-operative stress. A threefold increase in mean plasma beta-EP levels occurred 15 min after tail docking, and a maximal eight- to tenfold increase occurred in response to castration and/or mulesing with tail docking. Significant increments in mean plasma cortisol levels followed these surgical procedures with the maximal response 15 min after mulesing plus castration with tail docking. The physiologically active 'free' cortisol in plasma represents about 25% of the cortisol, as measured, and the two are highly correlated. At 24 h, beta-EP levels in all treated groups were similar to controls, although a small elevation in cortisol levels was still present in the lambs subjected to mulesing. Ultrafiltration of plasma extracts showed that peak beta-EP levels contained about 40% immunoreactivity from low molecular weight species (mol. wt less than 10,000). By specific radioimmunoassay and reverse-phase high-performance liquid chromatography this comprised about 75% beta-EP1-31, the most potent analgesic endorphin, 10% beta-EP1-27, and 15% alpha-N-acetyl-beta-EP. Increased beta-EP1-31 levels may modulate post-operative pain in lambs.     

Central ACTH deficit in degenerative and vascular dementia

Cerebrospinal fluid (CSF) concentrations of ACTH, beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) were measured in 15 patients affected by dementia, who underwent also a brain computerized tomography (CT), and in 13 age-matched healthy volunteers. ACTH CSF levels of patients (4.0 +/- 2.4 fmol/ml, M +/- SD) were significantly lower than in controls (9.8 +/- 5.0, P less than 0.01) the lowest values being found in Alzheimer type of dementia (ATD: 3.1 +/- 2.5) and in patients with radiological evidence of cortical atrophy (2.5 +/- 1.2), independently of the probable origin of dementia. Although beta-LPH and beta-EP levels of patients fell within normal range, they were lower in ATD than in dementia sustained on a vascular origin. There was no variation of either peptides concentration in relation to CT findings. These data indicate the ACTH impairment as typical of dementia, supporting in humans the positive role of this peptide on learning and mnesic functions. Moreover, the maintained CSF levels of both beta-LPH and beta-EP in the dementia sustained on a vascular origin, while lower values were found in ATD, could represent a differentiation between vascular and degenerative diseases of the Central Nervous System (CNS).     

Autonomous beta-endorphin secretion from the pituitary neurointermediate lobe: in vivo studies

The existence of independent control mechanisms of beta-endorphin (beta-EP) secretion from the anterior (AP) and intermediate (NIL) pituitary lobes is now ascertained. The aim of this study was to evaluate the effect of surgical separation from the hypothalamus of the two pituitary lobes on beta-EP secretion. Two experimental models of surgical hypothalamo-pituitary disconnection were used: 1) rats with ablation of the medial basal hypothalamus (MBH); 2) rats bearing two entire ectopic pituitaries or two anterior pituitaries (APs) only, transplanted under the kidney capsule. In rats with MBH-ablation plasma beta-EP levels were significantly higher than in sham-operated controls. Plasma beta-EP levels increased in rats transplanted with entire pituitaries 3 days after surgery and were still elevated after 1 week. In rats transplanted with APs only, no significant beta-EP changes in plasma were evident. In both experimental conditions no significant difference was present in beta-LPH plasma levels. Concentrations of beta-EP in the ectopic NILs decreased gradually after transplantation. In all these results indicate that that NIL but not the AP is capable, when is disconnected from the hypothalamus, or secreting autonomously beta-EP.     

Effects of acute and chronic methylphenidate administration on beta-endorphin, growth hormone, prolactin and cortisol in children with attention deficit disorder and hyperactivity

The effect of 5 mg/p.o. methylphenidate (MPH) challenge on beta-endorphin (beta-EP), growth hormone (GH), prolactin (Prl) and cortisol was investigated in 16 children suffering from attention deficit disorder with hyperactivity (ADDH) before and after 4 weeks MPH treatment. The study population consisted of 13 males and 3 females aged 6-11 years. All patients were drug free for at least 3 months prior to investigation. The severity of ADDH symptomatology and response to MPH chronic treatment was assessed using parent/teacher abbreviated Conners rating scale. Blood samples for beta-EP, cortisol, Prl and GH were drawn before initiation of treatment (basal pre-treatment level), 2 hours after MPH challenge, 4 weeks after MPH treatment (basal post-treatment level) and 2 hours after re-challenge with MPH. Chronic MPH treatment resulted in a decrease in basal Prl levels (5.5 +/- 2.8 vs 3.7 +/- 1.9 ng/ml; p less than 0.05). Pre-treatment challenge stimulates significantly both beta-EP (15.0 +/- 7.5 vs 12.5 +/- 5.3 pmol/l; p less than 0.05) and cortisol secretion (20.6 +/- 6.6 vs 12.6 +/- 5.8 micrograms/dl; p less than 0.05), and suppressed Prl secretion (4.0 +/- 1.5 vs 5.5 +/- 2.8 ng/ml; p less than 0.05). Re-challenge with MPH enhanced beta-EP levels (14.9 +/- 8.6 vs 10.6 +/- 5.0 pmol/l; p less than 0.05) but failed to affect cortisol, Prl and GH secretion. The acute and chronic neuroendocrine effects of MPH administration might be related to its dopaminergic and adrenergic agonistic activity. It might be that the stimulatory effect of single and repeated acute MPH administration on beta-EP release contributes to the beneficial effect of MPH treatment in ADDH children.     

Plasma beta-endorphin during fasting in man

To identify the effects of acute starvation on endogenous opioids in man, plasma beta-endorphin (beta-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma beta-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 +/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01; group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p less than 0.05, and remained at 5.05 +/- 0.65 pmol/l on the 10th day (group B: 0.05 less than p less than 0.1) during fasting. Group B had lower levels of plasma beta-EP on the 5th day of fasting than group A (p less than 0.05). However, serum cortisol levels changed similarly in both groups. Plasma beta-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma beta-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma beta-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.     

Effects of ovine corticotropin-releasing factor and vasopressin on plasma beta-endorphin, cortisol and behavior after minor surgery in sheep

The evidence for an analgesic effect arising from increased peripheral concentrations of beta-endorphin (beta-EP) in various animal species is controversial, and has not been fully evaluated in the sheep. To stimulate beta-EP release, ovine corticotropin-releasing factor (oCRF) and arginine vasopressin (AVP) were injected intravenously (iv) into a group of 12 out of 24 sheep, 15 min prior to minor surgery on all sheep. This brought about significant increases (P less than 0.01) in plasma beta-endorphin (beta-EP) and cortisol concentrations, relative to the non-injected control sheep, 15-30 min after injection. Ultrafiltration indicated that less than 30% of the released beta-EP immunoreactivity was present as higher molecular weight forms (mol. wt greater than 10,000) and that the majority (about 75%) of the beta-EP was probably bound to plasma proteins. By 75 min after injection there was no significant difference in plasma beta-EP or cortisol concentrations between the two groups of sheep. Consistent with previous observations the sheep showed a characteristic aversive behavior to the human handler following surgery, lasting several days. This behavior appeared to be unaffected by a pre-operative increase in peripheral plasma beta-EP, and may indicate that this increase in beta-EP was not sufficiently analgesic to block the cognitive response to the operation, or long-lasting enough to prevent the perception of post-operative soreness.     

Effect of myiasis and acute restraint stress on plasma levels of immunoreactive beta-endorphin, adrenocorticotrophin (ACTH) and cortisol in the sheep

Cutaneous myiasis in sheep arising from the activity of Lucilia cuprina larvae can result in significant physiological changes in susceptible animals. The stress imposed on the pituitary-adrenal axis of the sheep in response to myiasis and acute restraint is the subject of this investigation. Merino wethers were exposed to handling restraint, and blood sampling, during examination for blowfly strike; where necessary, they were treated for cutaneous myiasis. Significant changes in the plasma concentrations of immunoreactive beta-endorphin (beta-EP), ACTH and cortisol were found in sheep with extensive myiasis, as compared with unstruck sheep or those with only localized myiasis. In five susceptible sheep with extensive cutaneous myiasis, mean plasma levels of beta-EP, ACTH and cortisol were 307 +/- 71 pg ml-1, 953 +/- 58 pg ml-1 and 232 +/- 46 nmol l-1 respectively, compared with 818 +/- 89 pg ml-1, 641 +/- 41 pg ml-1 and 107 +/- 17 nmol l-1 in six unstruck sheep handled similarly. Whereas significant increases in plasma ACTH and cortisol can result from pituitary-adrenal responses to acute emotional or surgical stress, and are usually accompanied by a concomitant release of beta-EP from the pituitary, the present findings indicate a marked reduction in beta-EP levels and a significant increase in ACTH and cortisol in sheep following blowfly strike and acute handling restraint. This result suggests that cutaneous myiasis in susceptible sheep can alter the pituitary-adrenal response to acute restraint stress, and this could occur either by an alteration of precursor processing in the pituitary or by the selective release of ACTH.     

Expression of proopiomelanocortin-related peptides in human follicular fluid

In order to evaluate the expression of the opioid precursor proopiomelanocortin (POMC) in the ovarian follicle, we measured 6 of its main end-products in 23 follicular fluids. We coupled high performance liquid chromatography (HPLC) to specific radioimmunoassays. Seven follicles were immature (diameter less than 9 mm), 10 were obtained from superovulated patients during an in vitro fertilization-embryo transfer program (greater than 22 mm) and six were persistent follicles, collected during the luteal phase [15-31 mm, luteinized unruptured follicles (LUF)]. Follicular fluids were extracted by mean of Sep-pak cartridges and then purified by HPLC with a reverse-phase C-18 column eluted in a linear gradient with acetonitrile/0.01 M hydrochloric acid (from 18:82 to 40:60). Fractions were tested with specific antisera for ACTH (1-39), alpha-MSH, beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and gamma-endorphin (gamma-EP) immunoreactivities. No presence of beta-LPH, beta-EP and ACTH was confirmed, while gamma-EP, alpha-MSH and des-alpha-MSH were detected for the first time in follicular fluid. In every class of follicles shorter chain peptides predominate over their longer chain precursor. Immature follicles are characterized by the highest amounts of gamma-EP, ACTH, alpha-MSH and des-alpha-MSH if compared to superovulated and LUF. On the contrary, beta-EP amount was highest after superovulation. Apart from this finding, peptide levels in superovulated patients and LUF are similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise

Neuroendocrine and sympathoadrenal responses to exhaustive graded treadmill exercise were examined in 17 male subjects of varying degrees of fitness. The mean duration of exercise to exhaustion was 15.2 +/- 0.7 (+/- SE) min. Exercise duration was inversely correlated with baseline heart rate (P less than 0.05). Compared to standing baseline values, mean plasma norepinephrine and epinephrine levels increased 339% and 301%, respectively, in an integrated 2-min blood sample collected immediately after completion of exercise. Mean adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and prolactin levels increased 282%, 720%, 372%, and 211%, respectively, in an integrated 4-min blood sample beginning 2 min after completion of exercise. Cortisol levels increased 183% in the sample collected 17-21 min after exercise. The magnitude of these neuroendocrine responses to exercise was similar among individuals at the same relative intensity of exhaustive exercise, regardless of the duration of exercise. The exercise-induced increases of the pro-opiomelanocortin (POMC)-derived peptides, ACTH, beta-EP, and beta-LPH, were highly correlated with each other (P values less than 0.001), and were correlated with prolactin increases, (P values less than 0.05). During a 20-min recovery period after exercise, changes in heart rate, ACTH, and beta-LPH levels were correlated with duration of exercise, (P less than 0.01, P less than 0.03, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for serotonergic stimulation of pituitary beta-endorphin release: preferential release from the anterior lobe in vivo

Using gel filtration chromatography (Sephadex G-50) and radio-immunoassay for beta-endorphin (beta-END) and beta-lipotropin (beta-LPH) we investigated the site [anterior lobe (AL) vs. intermediate lobe (IL)] for serotonergic control of pituitary beta-END-like immunoreactivity (beta-END-LI) in the rat. Since the secretion of beta-LPH in vitro clearly distinguishes beta-END-LI release by the AL as compared to the IL, we interpreted changes in plasma levels of immunoreactivity resembling beta-LPH to reflect beta-END-LI release from the AL. Following the administration of L-tryptophan (200 mg/kg, 30 min, ip), a serotonin precursor, nearly all of the rise in total plasma beta-END-LI was due to the form of immunoreactivity resembling beta-LPH in molecular size. Similarly, 5-hydroxytryptophan (30 mg/kg, 30 min, ip), a serotonin precursor, and fluoxetine (10 mg/kg, 15 min, ip), a serotonin reuptake blocker, predominantly increased circulating levels of beta-LPH-sized immunoreactivity with little effect on beta-END-sized immunoreactivity. Quipazine (2.5 and 5.0 mg/kg, 30 min, ip), a serotonin receptor agonist, elevated plasma levels of both forms of beta-END-LI; however, the immunoreactive peak coeluting with beta-LPH was primarily affected, being increased 9.5-fold while that resembling beta-END was increased less than 1-fold. Immobilization stress (30 min) dramatically elevated plasma levels of both forms of immunoreactivity, however, a greater relative rise in beta-LPH than beta-END was observed. Intraventricular administration of 5,7-dihydroxytryptamine (75 micrograms, free base, 10 d), a serotonin neurotoxin, lowered plasma levels of both forms of immunoreactivity about equally in stressed animals. Further, dexamethasone, a synthetic glucocorticoid which selectively inhibits AL corticotroph secretion in vitro, attenuated the beta-LPH response to serotonergic activation in vivo. Together, these findings indicate that serotonergic drugs predominantly influence the release of beta-END-LI resembling beta-LPH and further suggest that serotonin neurons preferentially regulate the release of beta-END-LI from AL corticotrophs in vivo.     

Seasonal, circadian and episodic variations of human immunoreactive beta-MSH, ACTH and cortisol

The 24-hour profile of plasma levels of immunoreactive beta-MSH (IR-beta MSH), ACTH and cortisol was obtained at 15-min intervals in six normal males in summer and winter. In the radioimmunoassay used, dilution curves of human beta-MSH and human beta-LPH were not parallel. A seasonal variation in basal pituitary-adrenal secretion, with higher levels in winter than in summer, was demonstrated. A circadian rhythm was found to be significant for ACTH, IR-beta MSH and cortisol in all investigations. Whereas ACTH and cortisol patterns were largely concordant in all studies, there was a significant desynchronization of the circadian rhythm of IR-beta MSH as compared to ACTH in five cases. Eighty-three percent of the secretory spikes of cortisol but only 68% of the IR-beta MSH spikes were concomitant with an ACTH spike. Correlations between maximal levels of concomitant spikes were higher during the quiescent period of pituitary-adrenal secretion (22.00--04.00) for ACTH-cortisol whereas for ACTH-IR-beta MSH, highest correlations were found during the active early morning secretory phase (04.00--10.00). For the three plasma constituents studied, longer apparent half-lives were found to occur when the basal level before spiking was already elevated, suggesting that ACTH, beta-LPH and cortisol are secreted in bursts superimposed on a continuous basal secretion. Absolute increments of concentration appeared to be relatively independent of the level before spiking. It is suggested that the dissociations between ACTH and IR-beta MSH fluctuations in plasma observed here result from in vitro proteolysis of beta-LPH.     

Post-translational processing of pro-opiomelanocortin (POMC)-derived peptides during fetal monkey pituitary development. II. beta-Lipotropin (beta-LPH)-related peptides

We have studied the post-translational processing of POMC-derived peptides during fetal monkey pituitary development using immunoassay and reverse-phase high-performance liquid chromatography (RP HPLC). Whole pituitary glands obtained from Day 50 and 55 fetal monkeys and separated lobes From Day 65 to 155 were extracted, fractionated, and analyzed for beta-melanotropin (beta-MSH), midportion beta-endorphin (beta-EP), and acetylated beta-EP immunoactivity. Separated adult pituitary lobes were analyzed for comparison. At Day 50, POMC-containing cells were located in both the anterior and intermediate pituitary lobes by immunofluorescence staining, the majority of these cells were localized in the anterior lobe. The Day 50 and 55 whole pituitaries contained predominantly beta-lipotropin (beta-LPH), gamma-lipotropin (gamma-LPH), beta-EP(1-31), and 2.2-kda beta-MSH. No acetylated products were found in Day 50 whole pituitary extracts. By Day 55, carboxy-shortened and acetylated beta-EPs were barely detectable in whole pituitary extracts. These forms were more apparent in the Day 65 separated neurointermediate lobe (NIL) extracts, and were similar to adult proportions by Day 80. The adult anterior lobe contained predominantly beta-LPH, beta-EP, and gamma-LPH. Adult NILs contained almost exclusively 2.2-kda beta-MSH, alpha-N-acetyl beta-EP(1-31) and alpha-N-acetyl beta-EP(1-27). The production of 2.2-kda beta-LPH in the monkey NIL indicates that monkey beta-LPH is different from rat beta-LPH in that it must contain the paired-basic cleavage site required for the formation of 2.2-kda beta-MSH that is known to be lacking in rat beta-LPH. Another finding was that monkey beta-EP contains a Tyr residue at position 27 as found in human beta-EP but appears to have the rat Gln substitution at position 31. The post-translational processing patterns characteristic of each lobe were well established by midterm fetal development (Day 80).     

Hypothalamic-pituitary-adrenal responses to short-duration high-intensity cycle exercise

beta-Endorphin (beta-EP), adrenocorticotropin (ACTH), and cortisol plasma concentrations were examined before and after maximal exercise at four intensities [36, 55, 73, and 100% of maximal leg power (MLP)] by means of a computerized cycle ergometer. All intensities were greater than those eliciting peak O2 uptake for the individual subjects. Blood samples were collected at rest, immediately after exercise, and at 5 and 15 min postexercise. Significant (P less than 0.05) increases were observed at 36% MLP for beta-EP and ACTH immediately after exercise and at 5 and 15 min postexercise. Plasma cortisol increased at 36% MLP at 15 min postexercise. Blood lactate significantly increased at all postexercise collection points for exercise intensities of 36, 55, and 73% MLP and at 5 min postexercise for 100% MLP. beta-EP concentrations at 36% MLP were significantly correlated (r = 0.75) with capillary density (mm-2), and cortisol concentrations at 36% MLP were significantly correlated (r = 0.89) with percentage of type II muscle fibers. No other significant relationships were observed. These data show that brief, high-intensity exercise up to maximal power production results in a nonlinear response pattern in peripheral blood hormone concentrations. Furthermore, blood lactate levels do not appear to be related to hypothalamic-pituitary-adrenal hormone plasma concentrations at high exercise intensities.     

Effect of sandostatin on CRF-stimulated secretion of ACTH, beta-lipotropin and beta-endorphin.

The influence exerted by somatostatin on the secretion of ACTH and opioid peptides has still to be clarified. To gain further information on this issue, we performed in 10 normal volunteers two CRF tests (100 micrograms i.v.) one of which was preceded by s.c. injection of 100 micrograms of the long-acting somatostatin analogue SMS 201-995 (Sandostatin, Sandoz) (SMS), given 30 minutes before CRF. Premedication with SMS markedly inhibited the response of beta-EP to CRF, leaving unchanged the response of beta-LPH, ACTH and cortisol; mean incremental areas of beta-EP were 199.8 +/- 49.31 (SEM) vs 532.9 +/- 95.91 pmol 120 min (P less than 0.01) in the CRF test with and without SMS, respectively. To interpret the selective inhibitory effect of SMS on CRF-stimulated beta-EP secretion, it can be hypothesized that: a) the action of SMS was confined to a population of pituicytes preferentially secreting beta-EP; b) SMS interfered with the processing of POMC inhibiting the formation of beta-EP; c) SMS acted on extrapituitary, possibly peripheral, sources of beta-EP. In conclusion, this study indicates that, in man, somatostatin selectively inhibits the CRF-induced secretion of beta-EP, but not that of ACTH and beta-LPH, by an action that may be exerted at pituitary or extrapituitary level. This is a further example of dissociated secretion of POMC-derived peptides.     

Alterations in Extracellular and Tissue Levels of Biogenic Amines in Rat Brain Induced by the Serotonin2 Receptor Antagonist, Ritanserin

Systemic administration of ritanserin elicited rapid changes in dopamine (DA) and serotonin (5-HT) levels in both dialysate and neuronal tissue extracts. These effects occurred in both a site-selective and a dose-related manner. Increases in extracellular levels of DA and 5-HT in the nucleus accumbens were maximal at 120-140 min after treatment. A dose of 0.63 mg/kg of ritanserin elicited larger and more prolonged increases in extracellular DA and 5-HT levels than did the 0.3 mg/kg dose. By contrast, 0.63 mg/kg of ritanserin elicited no changes in either DA or 5-HT levels with dialysate collected from the striatum. Ritanserin also induced dose-related decreases in tissue levels of DA and 5-HT from the nucleus accumbens. The site specificity of action was again noted in that there were no dose-dependent decreases in tissue levels of DA or 5-HT measured from the striatum. Ritanserin exerted little effect on metabolite levels from either dialysate or tissue extracts. Taken together, these findings show that selective 5-HT2 receptor antagonism modulates DA and 5-HT neurotransmission in a specific manner. These actions appear to involve increased release of DA and 5-HT rather than significant changes in metabolism. These findings add further weight to the importance of 5-HT2 receptor interactions as an important component of antipsychotic activity.     

Plasma beta endorphin immunoreactivity: effects of sustained hyperglycemia with and without prior exercise

Seven healthy untrained men were studied to determine if sustained hyperglycemia is a stimulus to enhanced plasma levels of beta endorphin (beta-EP) and if so whether prior exercise affects that enhancement. After an overnight fast hyperglycemic glucose clamps were performed on 3 separate days: after prior rest, 2 h after exercise, and 48 h after exercise. Subjects exercised on a bicycle ergometer for 1 h at 150 W (64% VO2 max). Plasma glucose concentration was elevated in 4 continuous sequential stages to 7, 11, 20 and 35 mM with each stage lasting 90 min. Plasma glucose concentrations did not differ for each subject across the three clamps. beta-EP immunoreactivity was measured in arterialized venous blood samples using a specific and sensitive radioimmunoassay. Resting beta-EP at basal glucose concentrations was 3.8 +/- 0.7 fmol X ml-1 (mean +/- se) and prior exercise either 2h (3.2 +/- 0.5 fmol X ml-1) or 48 h (4.3 +/- 0.7 fmol X ml-1) before a clamp study did not effect these levels, (p greater than 0.05). At no time during the 3 hyperglycemic clamps did plasma levels of beta-EP differ significantly from resting values. At the highest level of hyperglycemia (35 mM) beta-EP was 3.1 +/- 0.2, 4.9 +/- 0.6 and 4.8 +/- 0.7 fmol X ml-1 in the resting, 2h and 48 h post exercise clamp studies respectively. The significance of these data is that this lack of a response is in distinct contrast to elevations of this peptide found during hypoglycemic states. We conclude that sustained hyperglycemia is not a stimulus to enhanced secretion of beta-EP into plasma and this lack of a response is not effected by prior exercise.