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Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species.
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PMID:Renin-angiotensin-aldosterone system of the normothermic marmot. 19 79

The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), beta-endorphin (beta EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D0), and before and after each day's racing (D1-D6). The mean daily heart rate (fc) was calculated from fc values recorded every minute during the race. The results showed the following: changes in mean fc [from 147 (SEM 3) to 156 (SEM 3) beats.min-1 according to the day] were not significant during the race. Diurnal variations in ACTH, beta EP and C were no longer apparent after the race: evening levels were higher than their respective D0 values during the race, except on D3 when there was a lack of response to exercise in the three hormones. Unlike ACTH and beta EP, pre- and postexercise C values on D1 and D2 were higher than those on the subsequent days (P less than 0.001). In contrast, there was a progressive accumulation of A and NA in pre- and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and beta EP were found especially on D3 and D6 (P less than 0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inter-relationships between pituitary-adrenal hormones and catecholamines during a 6-day Nordic ski race. 131 73

At present the origin of the signal(s) to initiate parturition remains unknown. Experimental studies in sheep have shown that interruption of the fetal hypothalamohypophyseal-adrenal axis will prolong gestation but no studies have shown prolongation of gestation after destruction of fetal neural structures. In this study we placed bilateral lesions of the paraventricular nucleus in five fetal sheep at 118 to 122 days' gestation. Cortiocotropin-releasing factor staining in the median eminence of the hypothalamus was markedly decreased after fetal paraventricular nucleus lesions. Paraventricular nucleus lesions prevented the fetal adrenocorticotropic hormone rise in response to hypotension and the normal predelivery increase in fetal plasma adrenocorticotropic hormone and cortisol and resulted in impaired fetal adrenal growth relative to the rest of the fetus. Lesioned fetuses had not been delivered at 157 days' gestation when they were removed by cesarian section to obtain tissue for histology. Four control fetuses were delivered at 146.5 +/- 0.9 days' gestation (mean +/- SEM). These findings indicate that a structure in the fetal brain, the fetal hypothalamic paraventricular nucleus, is necessary for parturition to occur.
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PMID:Bilateral destruction of the fetal paraventricular nuclei prolongs gestation in sheep. 165 27

Ovarian hyperandrogenism is a common disorder of women of reproductive age. The therapies that are presently available to treat this disorder are not uniformly effective or free of adverse effects. We conducted a prospective study of eight women receiving ketoconazole for a mean duration of 44 +/- 15 (SEM) weeks, as therapy of ovarian hyperandrogenism. Serum testosterone and hair growth rate declined in patients while on 600 to 1,000 mg ketoconazole daily. Menses normalized in seven of eight subjects during treatment. Ketoconazole therapy was not associated with a change in basal or postgonadotropin-releasing hormone stimulation gonadotropin levels. Basal cortisol levels were also unchanged on ketoconazole though responsiveness of cortisol to adrenocorticotropic hormone stimulation tended to be reduced. We conclude that ketoconazole can effectively reverse the biochemical and clinical abnormalities of ovarian hyperandrogenism. Until the issue of its safety is resolved, ketoconazole therapy is best limited to select individuals who agree to careful monitoring and the use of reliable birth control methods during treatment.
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PMID:Ketoconazole use in the treatment of ovarian hyperandrogenism. 216 44

The purpose of this study was to investigate the effects of physical training on the responses of serum adrenocorticotropic hormone (ACTH) and cortisol concentration during low-intensity prolonged exercise. Five subjects who had fasted for 12 h cycled at the same absolute intensity that elicited 50% of pre-training maximal oxygen uptake (VO2max), either until exhaustion or for up to 3 h, before and after 7 weeks of vigorous physical training [mean daily energy consumption during training exercise, 531 kcal (2230 kJ)]. In the pretraining test, serum ACTH and cortisol concentrations did not increase during the early part of the exercise. Increases in concentrations of both hormones occurred in all subjects when blood glucose concentration decreased during the later phase of the exercise. The mean values and SEM of serum ACTH and cortisol concentrations at the end of the exercise were 356 ng.l-1, SEM 79 and 438 micrograms.l-1, SEM 36, respectively. After the physical training, VO2max of the subjects improved significantly from the mean value of 50.2 ml.kg-1.min-1, SEM 2.5 to 57.3 ml.kg-1.min-1, SEM 2.0 (P less than 0.05). In the post-training test, exercise time to exhaustion was prolonged in three subjects. Comparing the pre- and post training values observed after the same length of time that the subjects had exercised in the pre-training test, the post-training values of serum ACTH (44 ng.l-1, SEM 3) and cortisol (167 micrograms.l-1, SEM 30) concentration were less than the pre-training value (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of physical training on the responses of serum adrenocorticotropic hormone during prolonged exhausting exercise. 217 89

To ascertain whether small shifts in plasma atrial natriuretic factor (ANF) exerted biological effects in hypertension, we studied the renal, hemodynamic, and hormonal effects of ANF [human ANF-(99-126)] infused at a dose (0.75 pmol/kg/min for 3 hours) that would induce changes in plasma ANF confined to the normal, resting range, in a group of six young men with uncomplicated, mild essential hypertension. During ANF infusions, the patients excreted 11.8 +/- 2.0 mmol (mean +/- SEM) sodium more than during the time-matched placebo phase natriuresis (p less than 0.001, mean increase of 53% above placebo values). Urinary excretion of cyclic guanosine monophosphate rose to more than double (212%, p less than 0.001) placebo values. Plasma renin activity (0.4 +/- 0.05 vs. 0.9 +/- 0.12 nmol/l/hr, p less than 0.0001) and aldosterone concentrations (102 +/- 4 vs. 184 +/- 47 pmol/l, p less than 0.05) were clearly suppressed during administration of ANF. Plasma norepinephrine also fell significantly below placebo values (268 +/- 17 vs. 439 +/- 35 pg/ml, p less than 0.05). Urine volume, the excretion of electrolytes other than sodium, hematocrit, effective renal plasma flow, glomerular filtration rate, and filtration fraction were unaffected by ANF. Similarly, plasma concentrations of epinephrine, arginine vasopressin, adrenocorticotropic hormone, and cortisol were unchanged. Blood pressure and heart rate were unchanged. Minor perturbations in plasma ANF concentrations exert clear biological effects in patients with mild essential hypertension. These data suggest that such minor shifts in plasma ANF are of physiological relevance in mild hypertension and probably contribute to volume homeostasis in this condition.
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PMID:Atrial natriuretic factor in hypertension: bioactivity at normal plasma levels. 252 19

To examine the effects of sustained (48-hour) hypoxemia on fetal and maternal adrenocorticotropic hormone concentrations and on maternal progesterone, uterine blood flow was reduced in eight sheep at day 128 of pregnancy by means of an adjustable Teflon clamp placed around the maternal common internal iliac artery. Control measurements were made in four animals in which the vascular clamp was not adjusted. Fetal PaO2 fell from 20.6 +/- 1.1 mm Hg (mean +/- SEM) to 16.6 +/- 0.6 mm Hg within 1 hour after application of the clamp and remained suppressed during 48 hours. There was a transient acidemia at 1 to 2 hours that had corrected by 8 hours. Fetal adrenocorticotropic hormone levels rose from 24 +/- 6 to 1320 +/- 205 pg/ml at 2 hours but decreased by 16 hours. Measured by high-pressure liquid chromatography, more than 95% of immunoreactivity corresponded to adrenocorticotropic hormone1-39. Fetal cortisol levels rose by 6 hours and remained elevated through 48 hours. Maternal adrenocorticotropic hormone, cortisol, and progesterone levels were unchanged during the study period. We conclude that fetal hypoxemia-acidemia after restriction of uterine blood flow provokes fetal adrenocorticotropic hormone release, but the elevation in adrenocorticotropic hormone is not sustained. However, the level of fetal cortisol rises progressively, consistent with fetal adrenal activation.
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PMID:Fetal and maternal endocrine responses to prolonged reductions in uterine blood flow in pregnant sheep. 254 Jun 57

The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of beta-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were assessed in 17 trained, male runners before and after running the longest possible distance within 12 min (i.e., the Cooper test). Each runner participated twice in the test (double-blind cross-over design), with a 1-week interval--with or without an injection of the opiate antagonist naloxone (0.8 mg i.v.). The average (SEM) distance reached was 3,198 (45) m in the naloxone test and 3,240 (38) m in the placebo test. The BEP increased significantly during the tests by a factor of 4.1 on naloxone and by 2.8 on placebo (from the normal resting averages of 1.7 and 2.1 pmol/l, respectively). The ACTH also increased significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of 19.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle pain was enhanced with naloxone. The increased perception of pain did not decrease the athletes ability to perform in terms of the distance run. We conclude that endogenous opiates are involved in the perception of pain associated with exhaustive exercise and may subserve psychological rather than physiological functions during exercise.
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PMID:Opioid involvement in the perception of pain due to endurance exercise in trained man. 254 82

The content and biosynthesis of aldosterone and cortisol were examined and compared in the aldosterone-producing adenomas and adjacent adrenal glands from patients with primary aldosteronism that resulted from solitary, benign adrenocortical tumors (0.8 to 32.3 gm). Histologic examination of the six aldosterone-producing adenomas studied confirmed a predominance of cells resembling zona fasciculata rather than zona glomerulosa, as reported in previous studies. Measurement by radioimmunoassay of the tissue content of steroids preformed in vivo demonstrated that aldosterone was present in concentrations 8 times higher in aldosterone-producing adenomas (1.5 +/- 0.5 micrograms/gm tissue; mean +/- SEM) than in adrenal glands (0.2 +/- 0.06 micrograms/gm tissue). Cortisol concentration in aldosterone-producing adenomas (5.4 +/- 1.4 micrograms/gm tissue) was approximately one third that in adrenal glands (15.8 +/- 6.3 micrograms/gm tissue), but cortisol was by far the major steroid in both types of tissue. In vitro, the most important metabolic product quantitatively from 4-carbon 14-labeled cholesterol incubated with mitochondria plus microsomes and from 4-14C-labeled pregnenolone incubated with tissue slices was cortisol, formed in a time-dependent manner in both types of preparations; cortisol synthesis greatly exceed that of aldosterone in adrenal glands, but even in aldosterone-producing adenomas the formation of cortisol was at least 5 times greater than that of aldosterone. The fasciculata structure and dual biosynthetic capacity of aldosterone producing adenomas for cortisol and aldosterone are interpreted in the light of developing concepts of the roles of adrenocorticotropic hormone and of alterations in the microenvironment of the cell in the zonal differentiation of the normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Content and biosynthesis of cortisol in aldosterone-producing adenomas. 275 1

To examine the role of parturition on lung maturation in sheep, we studied parameters of lung development in singleton fetuses treated with pulsatile adrenocorticotropic hormone or saline solution from day 127 or twin pregnancies in which one fetus only received pulsatile adrenocorticotropic hormone from day 127 until labor occurred. These parameters were compared with those of term fetuses (145 days). Pulsatile adrenocorticotropic hormone provoked labor in a mean (+/- SEM) of 102.6 +/- 6.6 and 181.0 +/- 18.0 hours in single and twin pregnancies, respectively. Adrenal/body weight ratios increased similarly in adrenocorticotropic hormone-treated single and twin fetuses at delivery, and basal cortisol levels were two- to threefold higher prepartum in adrenocorticotropic hormone-treated fetuses. Little change in plasma cortisol levels occurred in singletons treated with saline solution or in twins not infused with adrenocorticotropic hormone. The lung weight/body weight was not altered in any group. Lung distensibility and stability were doubled to term values in fetuses treated with pulsatile adrenocorticotropic hormone compared with controls and untreated twins. Mean lavage phosphatidylcholine levels rose from 0.07 to 0.11 mg/gm in saline solution-treated or untreated fetuses to 0.20 to 0.23 mg/gm in pulsatile adrenocorticotropic hormone-treated singletons or twins, compared with 0.63 mg/gm at term. Phosphatidylcholine production increased from 0.51 dpm/gm/hr in saline solution-treated fetuses to 0.73 and 0.89 dpm/gm/hr in the single and twin pulsatile adrenocorticotropic hormone-infused fetuses, respectively; phosphatidylcholine production was 0.62 dpm/gm/hr in the noninfused twin. Lungs of twins treated with pulsatile adrenocorticotropic hormone were morphologically more mature than those of untreated twins. We conclude that fetal endocrine responses to exogenous adrenocorticotropic hormone, rather than the stimuli associated with labor per se, are responsible for lung maturation in the fetal sheep.
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PMID:Discordant accelerated pulmonary maturation after adrenocorticotropic hormone-induced labor in twin sheep fetuses. 284 75


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