Plasma concentrations of adrenocorticotropin-related peptides in lambs injected with ovine corticotropin releasing factor or vasopressin

Synthetic ovine corticotropin-releasing factor (oCRF) and arginine vasopressin (AVP) were intravenously injected each alone or in combination (each peptide: 1 microgram/kg body weight) in lambs on days 1, 3, 7 and 20 after birth. Plasma samples were collected just before and 10 and 30 min after injection. Plasma concentrations of cortisol and aldosterone were measured. Adrenocorticotropin (ACTH)-related peptides were isolated by Sephadex G50 column chromatography and measured by radioimmunoassay. Three different peaks with an ACTH immunoreactivity were found in lamb plasma: a "big" ACTH molecular form (Mr = 30,000), an "intermediate" (Mr = 8000) and a "little" (Mr = 4500). In 1 and 3 days-old lambs, both CRF and AVP increased preferentially "intermediate" ACTH. In 7 and 20 days-old lambs, an increase in "little" ACTH occurred after CRF whereas "intermediate" ACTH rose after AVP. The rise in plasma levels of different molecular forms of ACTH after stimulation by CRF or AVP could suggest that the biological pathway of ACTH synthesis, storage and release may occur in different intracellular pools or rather in different pituitary cells. Intermediate ACTH stimulated adrenal secretion of cortisol as soon as the first day of postnatal life and increased plasma aldosterone concentration in 7 and 20 day-old lambs. At these stages aldosterone level did not change after a rise in "little" ACTH.     

Pituitary and adrenal responses to ovine corticotropin releasing factor and vasopressin injected into young and adult guinea-pigs

Comparison of effects of synthetic ovine corticotropin releasing factor (oCRF), Arginine-Vasopressin (AVP) and the combination of both peptides have been tried in adult and 7-days-old guinea-pigs. On plasmas collected 15 min after interscapulary injection, cortisol, aldosterone and ACTH were measured. The different circulating forms of ACTH were isolated by Sephadex G50 column chromatography, with 1% formic acid and measured by radioimmunoassay. Thus, in the guinea-pig plasma, we detected three immunoreactive forms of ACTH: a "big" molecular form (Mr greater than 20000), an "intermediate" (Mr = 9500) and a "little" ACTH form (Mr = 4500) which was eluted in the same fractions as human 1-39 ACTH. In adult guinea-pigs, CRF increased total ACTH and the "intermediate" form and also plasma cortisol concentrations whereas AVP remained without significant effect excepted a rise in cortisol levels. Injected together, CRF and AVP enhanced plasma concentrations of total ACTH, of the three circulating forms and of cortisol. In 7-days-old guinea-pigs, both CRF and AVP increased plasma concentrations of total, of "intermediate" ACTH and of cortisol and aldosterone whereas the combination of both peptides enhanced dramatically plasma concentration of total ACTH suggesting a magnifying effect of AVP on CRF activity still more efficient in young than in adult guinea-pigs.     

ADRENAL FUNCTION IN WILD AND REHABILITATED PACIFIC HARBOR SEALS (PHOCA VITULINA RICHARDII) AND IN SEALS WITH PHOCINE HERPESVIRUS-ASSOCIATED ADRENAL NECROSIS

Adrenal function in harbor seals (Phoca vitulina richardii) was evaluated using adrenocorticotrophic hormone (ACTH) stimulation tests and fecal cortisol levels. The effect of ACTH administration on plasma cortisol and aldosterone levels in five free-living and 14 rehabilitated harbor seal pups was determined using enzyme immunoassay and radioimmunoassay, respectively. In free-living seals, injection of ACTH caused a significant increase in mean plasma cortisol but not of mean aldosterone levels 60 min postinjection. In these seals, mean initial plasma aldosterone was significantly higher than initial levels in rehabilitated seals, while initial cortisol levels were similar. Of the rehabilitated seals, eight died with adrenal cortical necrosis associated with herpesvirus inclusions, while six lived to be released. In the seals that were released, both mean initial cortisol levels and response to ACTH decreased through rehabilitation. In the seals that died, mean initial cortisol and response to ACTH increased through rehabilitation. The differences between initial cortisol levels in seals that lived and those that died were significant at weeks two and four of rehabilitation but not at the week of admission. There was considerable individual variation in initial plasma aldosterone levels and responses to ACTH, although initial aldosterone levels were significantly higher in rehabilitated seals that died than in seals that lived. Seals with adrenal necrosis associated with herpesvirus infection did not have decreased adrenal hormone responses to ACTH. Differences between initial hormone levels and responses to ACTH in different groups of seals may be associated with differing stress levels. Fecal cortisol assays were not a useful method of assessing adrenal function in these seals, as measured levels did not correlate with plasma cortisol levels.     

Plasma ACTH, cortisol and aldosterone concentrations in chronically cannulated ovine fetuses and in lambs injected with ovine corticotropin releasing factor

Synthetic oCRF was intravenously injected into 3 groups of 5 chronically cannulated ovine fetuses in utero on days 120, 130 and 137 of gestation (10 micrograms/fetus). The respective twin fetuses were used as controls. Ovine CRF was also intravenously injected into 4 groups of 6 lambs on days 1, 3, 7 and 20 after birth (5 micrograms/kg bw). Fetal plasma ACTH and cortisol concentrations increased significantly following oCRF as early as 120 days of gestation without changing maternal plasma cortisol concentrations. The ACTH and cortisol response to CRF increased gradually on stages 130 and 137 of gestation, but on the other hand, plasma aldosterone did not change. In newborns, after oCRF, the pituitary response gave peak values at 10 min for plasma ACTH and adrenal response gave peak values at 15 min for plasma cortisol. Between 1 and 20 days, plasma ACTH and cortisol changes after oCRF decreased in older animals while aldosterone level remained unchanged. In animals receiving both treatments on days 1 and 20, plasma cortisol levels were increased for longer than in animals treated once.     

Effect of metoclopramide on adrenal secretion in sheep: influence of dexamethasone and sodium intake

Metoclopramide, a competitive dopamine antagonist, stimulates aldosterone in man and monkey without affecting cortisol secretion. In sheep, metoclopramide also stimulates aldosterone but ist action on adrenocortical secretion is more controversial. To clarify the action of metoclopramide in conscious sheep, the response of plasma aldosterone, cortisol, angiotensin II and potassium were studied after 0.16 and 0.64 mg/kg metoclopramide, with and without pretreatment with dexamethasone. The effect of sodium status on the response was also studied by repeating the experiments after 7 days of dietary sodium restriction. In the absence of dexamethasone, plasma aldosterone was significantly increased by metoclopramide in both sodium-replete and restricted sheep. In sodium-replete sheep, plasma cortisol was also increased by 0.64 mg/kg, and by both doses when salt-restricted. However all cortisol responses were completely suppressed by dexamethasone pretreatment. Dexamethasone also suppressed the aldosterone response to metoclopramide in sodium-replete but not in sodium-restricted sheep where significant responses of aldosterone to both doses of metoclopramide still occurred without changes in plasma angiotensin II or potassium. While a nonspecific stress effect of metoclopramide can contribute to the aldosterone response, these results show that the sheep's adrenal glomerulosa is capable of responding to metoclopramide without change in ACTH, angiotensin or potassium.     

Differential effects of mineralocorticoid blockade on the hypothalamo-pituitary-adrenal axis in pregnant and nonpregnant ewes

During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus.     

Baseline,diurnal variations,and stress-induced changes of stress hormones in three captive beluga whales,Delphinapterus leucas

Concentrations of plasma adrenocorticotropic hormone (ACTH), cortisol, and aldosterone were investigated in three adult beluga whales (Delphinapterus leucas), held in a large outdoor public aquarium exhibit. The purpose of this study was to evaluate resting concentrations of these hormones and associated diurnal variations with routine interactions and medical procedures. Resting blood samples were collected voluntarily from the ventral fluke veins at predetermined times of the day to evaluate diurnal changes in analyte concentrations. In addition, hematology and serum chemistry analyses were performed to monitor health status and evaluate changes related to physical exam procedures. Analogous sampling was conducted during out-of-water physical examinations and before and after wading-contact sessions (WCS). Baseline stress hormone concentrations (± SD) were as follows: plasma ACTH (8.41 ± 5.8 pg/mL), serum cortisol (1.80 ± 0.71 g/dL), and serum aldosterone (11.42 ± 5.5 pg/mL). Plasma ACTH and cortisol concentrations were consistently higher in early morning than evening, while aldosterone was higher in the evening. All stress-related hormones were significantly elevated during physical examination. Plasma ACTH concentrations were most increased, 5–10-fold, during physical examination, whereas cortisol and aldosterone showed 2–4-fold elevations. Stress response analytes measured during the WCS did not differ significantly from baseline concentrations.     

Influence of psychosomatic stress in pregnant guinea-pigs on fetal lipid metabolism

After a psychosomatic stress applied to pregnant guinea-pigs, 7 or 1 day before term, plasma cortisol and non-esterified fatty acid levels increased immediately in mother and fetus. Plasma levels of cortisol and non-esterified fatty acids in newborns of mothers stressed 1 day before term were lower than in newborns of control mothers. The prenatal stress changed composition of triacylglycerol and phospholipids in newborn liver by inhibiting the postnatal increase of triacylglycerol and phospholipid stearic acid and by inhibiting the postnatal decrease in phospholipid palmitic, palmitoleic, linolenic and arachidonic acids.     

Influence of morphine treatment in pregnant rats on the mineralocorticoid activity of the adrenals in their neonates

Exposure of pregnant rats to morphine, from day 11 to day 18 of gestation, was previously reported to induce both an adrenal atrophy and hypoactivity of the glucocorticoid function in newborns at term, but did not affect, in vitro, the responsiveness of those glands to adrenocorticotrophin hormone (ACTH) concerning corticosterone release. Moreover, these effects were mediated by maternal hormones from the adrenal glands. In the present work, we investigated the effects of a prenatal morphine exposure on the mineralocorticoid activity of the adrenals in neonates. The first aim of the present study was to determine in these newborns 1) the adrenal and plasma aldosterone concentrations at birth time and during the early postnatal period 2) the plasma levels of Na+ and K+ at birth time, 3) the in vitro responsiveness of the newborn adrenals to angiotensin II (A(II)) and ACTH. The second aim of our study was to investigate the mineralocorticoid activity of the adrenals in newborns from adrenalectomized mothers treated with morphine during gestation. According to present data morphine given to intact mothers induced in newborns a severe adrenal atrophy but increased adrenal aldosterone content and plasma aldosterone level. However, prenatal morphine was unable to affect significantly Na+/K+ ratio in both mothers and newborns. In vitro, the adrenals of neonates from morphine-treated mothers were unresponsive to An and ACTH for promoting aldosterone release; in contrast, aldosterone secretion was significantly stimulated by high potassium levels (55 mEq). Maternal adrenalectomy performed one day before the beginning of morphine treatment prevented morphine-induced adrenal atrophy but was unable to affect significantly the adrenal mineralocorticoid function of the offspring. Such data suggest that a prenatal morphine exposure stimulated both aldosterone synthesis and release in neonates. However, this basal hyperfunction did not appear to be coupled with an enhanced adrenal responsivity to AII or ACTH. Prenatal morphine-induced hyperactivity of the mineralocorticoid function of the newborn adrenals, which drastically contrast with hypoactivity of the glucocorticoid one, was independent of adrenal factors from maternal origin.     

ADRENOCORTICAL FUNCTION IN PINNIPED HYPONATREMIA

Potentially fatal sodium imbalance occurs in captive and free-ranging pinnipeds and is associated with a variety of stressors. We sought to determine the role of adrenal hormones, principally aldosterone, in the development of this condition. To induce hyponatremia, two ringed seals, Phoca hispida , were maintained in fresh water and fed a low-sodium diet; as controls, two other ringed seals were held in salt water and received a salt-supplemented diet. After 3–6 mo, adrenocorticotropic hormone (ACTH) was used to assess adrenocortical function. In normonatremic control seals, ACTH produced a 2-j-fold increase in circulating cortisol and a 7-fold increase in aldosterone. One of the experimental seals maintained normal plasma sodium levels, and ACTH elicited an exaggerated aldosterone response. The other salt-deprived seal became hypo-natremic, and ACTH had little effect on plasma aldosterone levels. An ACTH stimulation test performed on a spontaneously hyponatremic harp seal, P. groenlandica , which had been maintained in a salt-rich environment, failed to elicit cortisol or aldosterone secretion from the adrenal cortex. This study demonstrated the unusual sensitivity of the seal's zona glomerulosa to central stimulation, providing a mechanism through which the stress response might exhaust adrenal hormone reserves or desensitize the cortex to other physiological stimuli.     

Effects of neurotrophic stress on maternal metabolism and binding of plasma cortisol in late pregnant guinea-pigs and their fetuses

The maternal metabolic clearance rate (MCR) and the binding of cortisol in the plasma of fetus and mother were estimated 8 days before term in conscious pregnant guinea-pigs, control or subjected to a neurotrophic stress (they were immobilized for 3 h in a dark room in front of an intermittent luminous flash). The maternal MCR of cortisol dropped during pregnancy related to an increase in corticosteroid binding globulin (CBG) and the stress mimicked these changes with a decrease in MCR and a rise in CBG. The increase in cortisol concentrations occurring in the fetal plasma after maternal stress could be related to the increase in free cortisol in the stressed mother. Nevertheless, although the fetal CBG did not rise after maternal stress, the increase in free cortisol in the fetal plasma remained moderate, due to the numerous free sites of CBG and albumin for cortisol.     

Differences in cortisol, aldosterone and testosterone responses to ACTH 1-17 administered at two different times of day

The effects of 100 micrograms, i.m. of the analog ACTH 1-17 administered at 0800 and 1800 on the secretion of cortisol, aldosterone and testosterone have been studied in normal subjects: 8 male and 8 female. The group as a whole and the males had significantly greater absolute and percent increments in plasma cortisol after administration at 1800. In the females, there was only a greater percent increment in cortisol after the evening administration. The heptadecapeptide always significantly stimulated serum aldosterone, with no difference between the two times of administration. In the females, ACTH 1-17 significantly stimulated testosterone, with a more protracted secretion after the evening administration. In the males, there was always a significant testosterone decrease after the administration of the drug, with no difference between morning and evening. In conclusion, 100 micrograms i.m. of the analog ACTH 1-17 stimulates cortisol secretion more when given during the circadian nadir of plasma cortisol, but only in men. ACTH 1-17 increases testosterone in women and decreases it in men, whereas it seems to increase aldosterone secretion in both sexes.     

Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation

This study examined the effects of dexamethasone treatment on basal hypothalamo-pituitary-adrenal (HPA) axis function and HPA responses to subsequent acute hypoxemia in the ovine fetus during late gestation. Between 117 and 120 days (term: approximately 145 days), 12 fetal sheep and their mothers were catheterized under halothane anesthesia. From 124 days, 6 fetuses were continuously infused intravenously with dexamethasone (1.80 +/- 0.15 microg.kg(-1).h(-1) in 0.9% saline at 0.5 ml/h) for 48 h, while the remaining 6 fetuses received saline at the same rate. Two days after infusion, when dexamethasone had cleared from the fetal circulation, acute hypoxemia was induced in both groups for 1 h by reducing the maternal fraction of inspired O2. Fetal dexamethasone treatment transiently lowered fetal basal plasma cortisol, but not ACTH, concentrations. However, 2 days after treatment, fetal basal plasma cortisol concentration was elevated without changes in basal ACTH concentration. Despite elevated basal plasma cortisol concentration, the ACTH response to acute hypoxemia was enhanced, and the increment in plasma cortisol levels was maintained, in dexamethasone-treated fetuses. Correlation of fetal plasma ACTH and cortisol concentrations indicated enhanced cortisol output without a change in adrenocortical sensitivity. The enhancements in basal cortisol concentration and the HPA axis responses to acute hypoxemia after dexamethasone treatment were associated with reductions in pituitary and adrenal glucocorticoid receptor mRNA contents, which persisted at 3-4 days after the end of treatment. These data show that prenatal glucocorticoids alter the basal set point of the HPA axis and enhance HPA axis responses to acute stress in the ovine fetus during late gestation.     

Maternal dietary folate and/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring

Maternal vitamin deficiencies are associated with low birth weight and increased perinatal morbidity and mortality. We hypothesize that maternal folate and/or vitamin B₁₂ restrictions alter body composition and fat metabolism in the offspring. Female weaning Wistar rats received ad libitum for 12 weeks a control diet (American Institute of Nutrition-76A) or the same with restriction of folate, vitamin B₁₂ or both (dual deficient) and, after confirming vitamin deficiency, were mated with control males. The pregnant/lactating mothers and their offspring received their respective diets throughout. Biochemical and body composition parameters were determined in mothers before mating and in offspring at 3, 6, 9 and 12 months of age. Vitamin restriction increased body weight and fat and altered lipid profile in female Wistar rats, albeit differences were significant with only B₁₂ restriction. Offspring born to vitamin-B₁₂-restricted dams had lower birth weight, while offspring of all vitamin-restricted dams weighed higher at/from weaning. They had higher body fat (specially visceral fat) from 3 months and were dyslipidemic at 12 months, when they had high circulating and adipose tissue levels of tumor necrosis factor α, leptin and interleukin 6 and low levels of adiponectin and interleukin 1β. Vitamin-restricted offspring had higher activities of hepatic fatty acid synthase and acetyl-CoA-carboxylase and higher plasma cortisol levels. In conclusion, maternal and peri-/postnatal folate and/or vitamin B₁₂ restriction increased visceral adiposity (due to increased corticosteroid stress), altered lipid metabolism in rat offspring perhaps by modulating adipocyte function and may thus predispose them to high morbidity later.     

The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage

Introduction

In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.

Methods

A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed.

Results

Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.

Conclusions

The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.     

Dexamethasone in resting and exercising men. II. Effects on adrenocortical hormones.

This study presents the reactions of adrenocorticosteroids (cortisol and aldosterone) and sex steroids [testosterone, androstenedione, and dehydroepiandrosterone and its sulfate (DHAS)] 1) to a dexamethasone (Dex) treatment, which is expected to lower steroid levels via the ACTH blockade, and 2) to an exercise bout at maximal O(2) consumption, which is expected to increase steroid production via ACTH stimulation. Consistent with the decrease in ACTH, all steroids except testosterone reacted negatively to Dex, independently of the dose (0.5 and 1.5 mg administered twice daily for 4.5 days). After exercise, plasma ACTH rose to 600% of basal value, resulting in a significant increase in aldosterone and adrenal androgens, but cortisol and DHAS were unaffected. This apparently surprising result can be explained by differences in peripheral metabolism: a theoretical calculation predicted that after 15 min the increase in hormone concentration may only reach 12% for cortisol and 2% for DHAS. For cortisol and adrenal androgens, assays were carried out using plasma and saliva. The consistent results obtained from the two matrices allow us to consider salivary assays as a useful tool for steroid abuse detection.     

Acute effects of mazindol on the secretion of ACTH, beta-lipotropin, beta-endorphin and cortisol in man

The effects of mazindol, an anorexiant, on the secretion of anterior pituitary and adrenocortical hormones were examined in healthy male volunteers and in patients with Addison's disease. In healthy male volunteers, significant elevations in plasma ACTH, beta-endorphin, beta-lipotropin and growth hormone were induced by mazindol administration, though no changes were observed in plasma thyrotropin, luteinizing hormone, follicle-stimulating hormone or prolactin. Plasma ACTH increased in patients with Addison's disease, too. In addition, plasma cortisol increased, without a change in the plasma aldosterone levels after mazindol administration to normal subjects.     

Effect of prenatal stress on the pituitary-adrenal axis in blue foxes

Handling is a source of stress for farm bred blue foxes. The influence of handling during the late gestation period on the pituitary--adrenal axis was studied in 10-day old male and female blue foxes. Cortisol and progesterone were measured by radioimmunoassay in the plasma, adrenal homogenates, and in vitro incubates from animals of both sexes. Adrenals were incubated in vitro in the absence or presence of ACTH. In addition, the adrenal weight and plasma concentration of ACTH were assessed. In cubs of both sexes, the adrenal weight was decreased after prenatal stress. The plasma concentration of progesterone and the adrenal cortisol in vitro production were elevated in the prenatally stressed female cubs, as compared to the control, along with the adrenal progesterone in vitro production in prenatally stressed male cubs. The adrenal cortisol and progesterone content and plasma ACTH and cortisol concentrations were not affected by prenatal stress. In conclusion, the results of this study suggest that the prenatal stress induced by handling pregnant vixens can affect the pituitary--adrenal axis in neonatal offspring, this effect being more pronounced in female cubs.     

Effects of a long-acting somatostatin analogue on pituitary-adrenocortical secretion in normal human subjects

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 micrograms SMS or placebo at 0830 h and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 micrograms or 63 micrograms) at 0900 h after 100 micrograms SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of 17-alpha-hydroxyprogesteronecapronate on sodium excretion and the renin-angiotensin-aldosterone-system in humans]

In seven healthy male subjects, a natriuretic effect of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHPC) was demonstrated. Three of these subjects were kept on an uncontrolled diet and were examined over a period of 12 days. To the remaining four subjects, a single dose of 250 mg 17 alpha-OHPC was given intramuscularly after four days of intake of a chemically defined diet (Vivasorb). In this second test procedure, blood samples were taken in the recumbent position every two hours throughout a period of 12 h after the injection. For two more days and during the days before the administration of 17 alpha-OHPC, blood was taken at 8 a.m. before getting up from bed in same intervals, urine was collected for analysis of sodium and potassium excretion. During the first 12 h after the injection of 17 alpha-OHPC, the urinary sodium/potassium ratio significantly increased in all subjects. Plasma renin activity showed no characteristic changes at this time, whereas the plasma concentrations of aldosterone and cortisol decreased. The decrease of cortisol concentration started immediately after the injection and was more pronounced than that of plasma aldosterone. During the following 36 h, renin activity as well as aldosterone and cortisol concentrations in plasma showed an increase; in contrast, the sodium/potassium ratio decreased. On the basis of these results, the following effects of 17 alpha-OHPC are discussed: (1) an acute natriuresis which may be due to a competitive inhibition of aldosterone at the renal tubules, and (2) an inhibition of pituitary ACTH secretion or of adrenal steroid biosynthesis.