Long-acting ACTH Research Articles

Role of Long-Acting Porcine Sequence ACTH (Acton Prolongatum) Stimulated Cortisol in Assessing Glucocorticoid Status in COVID-19 Patients.

Conflicting research on cortisol levels and COVID-19 mortality prompted this study to comprehensively assess glucocorticoid status, its links to severity and outcomes, and the role of Acton prolongatum-stimulated cortisol. This is a prospective observational study, conducted in 100 RT-PCR-positive COVID-19 patients of mild, moderate, and severe grades from June 2021 to May 2023. Random cortisol, plasma ACTH, and action prolongatum stimulated cortisol were measured, categorized, and analyzed. Among 100 patients, 25 had severe disease, 35 had moderate disease, and 40 had mild disease. In the same study group, 88 recovered and 12 expired from the COVID-19-related cause. The median random basal serum cortisol level (median (IQR): 10.2 (8) vs. 11.6 (9.7) vs. 16.2 (9.5) mcg/dl; P value 0.06), median delta value (median (IQR): 6.3 (5.8) vs. 7.6 (4.8) vs. 10.9 (5.6) mcg/dl; P value < 0.001), and median plasma ACTH (median (IQR): 13 (14.7) vs. 14.4 (14.1) vs. 22.3 (13) pg/ml; P value = 0.002) were lower in severe group subjects than in the moderate and mild group. When patients were labeled as adrenal insufficiency based on random basal serum cortisol < 10 mcg/dl or delta value < 9 mcg/dl, 48% of patients had adrenal insufficiency. There was a linear correlation between random basal and ACTH-stimulated cortisol (r = 0.908, P value < 0.001). The study highlights the significance of adrenal function in COVID-19 prognosis and suggests for routine random cortisol and ACTH assessments for glucocorticoid evaluation.

Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver.

There are no reliable methods in clinical practice to diagnose adrenal insufficiency (AI) in patients with cirrhosis owing to variable cortisol-binding protein levels. This leads to unreliable results in ACTH stimulated serum cortisol test. We aimed to estimate the long-acting porcine (LA)ACTH-stimulated serum and salivary cortisol levels of patients at different stages of cirrhosis using second generation electrochemiluminescence and to determine the prevalence of true adrenal insufficiency in these patients. We included 135 noncritical patients with cirrhosis (45 each from CHILD A, Band C) and 45 healthy controls. Serum and salivary samples were collected at baseline in the morning and at 1and 2 h after LA-ACTH injection. In healthy subjects, the 2.5th centile of 2 h ACTH stimulated serum and salivary cortisol were 19.8and 0.97 μg/dL, which were used as cut-offs for defining AI based on serum and saliva respectively. The median (interquartile-range) 2-h stimulated salivary cortisol in Child A, B, C categories and controls were 1.36(1.23-2.38), 1.46(1.18-2.22), 1.72(1.2-2.2) and 2.12(1.42-2.72) μg/dLrespectively. Six subjects (4.4%) were diagnosed to have AI based on stimulated salivary cortisol cut-off, whereas 39 (28.9%) cirrhosis subjects had inadequately stimulated serum cortisol. Three patients (symptomatic) required steroid replacement therapy. Hypoalbuminemia was identified as a major risk factor for the misdiagnosis of adrenal insufficiency by serum cortisol-based testing. Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver. Stimulated salivary cortisol is a promising investigation for evaluation of adrenal function in cirrhosis and more studies are required for its further validation before clinical use.

Long-acting Porcine Sequence ACTH (Acton Prolongatum) Stimulation Test is a Reliable Alternative Test as Compared to the Gold Standard Insulin Tolerance Test for the Diagnosis of Adrenal Insufficiency.

Context:As synacthen use is not licensed in India and there are concerns about the safety of the insulin tolerance test (ITT), an alternative dynamic test to diagnose adrenal insufficiency (AI) is required.Objective:The study aimed to evaluate the diagnostic performance of the Acton Prolongatum stimulation test (APST) with a standard ITT for the diagnosis of AI.Design:Prospective study comparing two diagnostic tests.Participants:Six healthy volunteers and 53 suspected or known AI patients.Measurements:Serum cortisol response to ITT and APST.Results:The median (95% confidence interval [CI]) peak cortisol levels among healthy volunteers in ITT and APST were 17 (14.58–19.08) and 30.5 (22.57–34.5) μg/dL. Of the 53 patients (age: 39.6 ± 9.38 years; females: 38 [71.1%]), 34 had AI (peak ITT serum cortisol < 14.5 μg/dL) whereas 19 had a normal hypothalamic-pituitary-adrenocortical (HPA) axis. In the receiver operator characteristic curve analysis, 60-min APST cortisol had an area under the curve of 0.984 (95% CI: 0.904–1.00, P < 0.0001). The best accuracy was obtained at a cut-off of 16.42 μg/dL (sensitivity: 97.7% [95% CI: 87.7–99.9%]; specificity: 100% [69.2-100%]). Forty-three of the 53 patients with suspected AI had hypoglycemic symptoms during ITT and two of them required intravenous dextrose, whereas, none had adverse events during APST. The ITT was incomplete in two patients whereas all completed APST.Conclusions:APST is a simple, safe, and reliable alternative to ITT for the diagnosis of AI; 60-min serum cortisol of 16.42 μg/dL in APST best distinguishes the AI patients from those with adequate cortisol response.

Long-acting porcine sequence ACTH in the diagnosis of adrenal insufficiency: a cost-effective alternative to the ACTH1-24 test.

While the ACTH1-24 test has some well-documented shortcomings, it is the most widely used test to diagnose primary and secondary adrenal insufficiency. However, this synthetic ACTH preparation is not readily available in some countries. Research from India has demonstrated that using a long-acting porcine sequence ACTH has similar diagnostic performance to ACTH1-24 at around 25% of the cost. This may allow access to a robust test for adrenal insufficiency to developing countries and potentially allow thousands of patients to be identified and appropriately treated.

Long-acting intramuscular ACTH stimulation test for the diagnosis of secondary adrenal insufficiency in children.

Background The diagnosis of adrenal insufficiency (AI) is based on the basal and stimulated levels of serum cortisol in response to the short Synacthen test (SST). In patients with secondary AI (SAI) due to hypothalamic-pituitary-adrenal (HPA) axis defects, the SST has been validated against the insulin tolerance test (ITT), which is the gold standard. However, injection Synacthen is not easily available in some countries, and endocrinologists often use Acton-Prolongatum (intramuscular [IM] long-acting adrenocorticotropic hormone [ACTH]) in place of Synacthen. There are no studies validating the use of IM-ACTH in children with suspected AI. We evaluated the diagnostic value of the IM-ACTH test against the ITT for the diagnosis of SAI in children. Methods All children with suspected growth hormone deficiency (GHD) undergoing a routine ITT were evaluated using the IM-ACTH test within 1 week. Results Forty-eight patients (36 boys/12 girls, age range: 5-14 years) were evaluated using both the ITT and the IM-ACTH test. Twenty-eight patients had a normal cortisol response (≥18 μg/dL, 500 nmol/L) in the ITT and 20 had low values. In patients with a normal cortisol response on the ITT, the peak value obtained after the IM-ACTH test was higher than that on the ITT (28.7 μg/dL [± 8.8] vs. 23.8 μg/dL [± 4.54], respectively; p=0.0012). Compared to the ITT, the sensitivity and specificity of the IM-ACTH test for the diagnosis of SAI at cortisol cut-offs <18 μg/dL (500 nmol/L) and <22 μg/dL (600 nmol/L) were 57.1% and 92.8%, and 100% and 73.5%, respectively. Conclusions A peak cortisol value <18 μg/dL on the IM-ACTH test is highly suggestive of SAI, whereas a value >22 μg/dL rules out SAI.

Glucocorticoid overexposure in neonatal life alters pancreatic beta-cell function in newborn foals1

Studies in humans and animals have linked abnormal programming of adult tissue function to excess glucocorticoids during perinatal development. The current study investigated the hypothesis that physiological variations in glucocorticoid concentrations during early neonatal life of the foal alter the secretory responses of the pancreatic β cells 2 and 12 wk after treatment. Spontaneously delivered foals received either saline or long-acting ACTH for 5 d from 1 d after birth to maintain an endogenous rise in cortisol concentrations. Starting at d 10, pancreatic β cell function was studied using an intravenous (i.v.) glucose tolerance test, an i.v. arginine challenge, and an i.v. tolbutamide challenge. The maximum increment in plasma insulin achieved in response to exogenous glucose was less in ACTH-treated foals at both 2 and 12 wk of age (P<0.05). By 12 wk of age, developmental changes also occurred in the magnitude and biphasic pattern of glucose-stimulated insulin release. The area under the insulin curve during the early phase of insulin secretion (0 to 30 min) was not different between the 2- and 12-wk-old animals but was significantly greater during the later phase (30 to 120 min) at 12 wk than at 2 wk (P<0.05). Arginine infusion induced a brief 5 to 15 min increase in plasma concentrations of insulin that was not different in saline- and ACTH-treated foals. The β-cell response to tolbutamide infusion was rapid and monophasic, and there was no difference (P>0.05) in the area under the insulin curve with treatment at 2 or at 12 wk. However, after tolbutamide, plasma insulin concentrations remained increased for a longer period in the ACTH-treated than in the saline-treated foals at 12 wk of age (P<0.05). Hence, this is the first study to show altered pancreatic β-cell function after ACTH-induced glucocorticoid overexposure during early postnatal life in foals.

The effect of long-acting ACTH on plasma corticosteroids, testosterone, and LH levels in the male pig.

Intramuscular injection of long-acting ACTH (10 micrograms/kg body weight) into male pigs, fitted with permanently indwelling jugular catheters, resulted in a significant rise of plasma corticosteroid concentrations for a period of between 0.5 and 20 hours after injection. Plasma testosterone levels were significantly increased between 60 and 120 min after ACTH administration. Between 6 and 12 hours after ACTH application, however, they were significantly depressed, evidencing a two phase effect of ACTH on testosterone levels. Plasma LH concentrations showed a slight but progressive decrease which was significant between 2.5 and 12 hours p.i. From these results it has been concluded that long-acting ACTH stimulates testosterone release. Because LH levels were depressed, they cannot have been responsible for the increase in plasma testosterone. The increase of plasma testosterone concentrations was not accompanied by a change of plasma prolactin levels.

Dual effects of prolonged ACTH stimulation on 4-hydroxyaminoquinoline 1-oxide-induced adrenocortical lesions in rats.

The effects of a long-acting synthetic ACTH on 4-hydroxyaminoquinoline 1-oxide (4HAQO)-induced adrenocortical lesions were investigated in female rats. A total of 140 6-week-old rats were divided into 4 equal groups, given a single s.c. injection of 7 mg/kg 4HAQO or vehicle, followed by repeated sc administration of the synthetic ACTH or no further treatment. Subgroups of 10 rats in each group were sequentially sacrificed at weeks 20, 30, and 40. Adenomas and adenomatous nodules developed in the adrenal cortex of animals receiving 4HAQO and the chronic ACTH stimulation. Both lesions were located in the deeper zones of the adrenal cortex adjacent to the medulla and were composed of large-sized, clear-type cells. From week 20, middle zone, cortical cystic degeneration, which mimics the age-associated degenerative change named adrenal peliosis, was frequently observed in the adrenal glands of animals treated with 4HAQO alone. Its development was inhibited by ACTH. In the control animals, peliotic changes occurred at low incidence and only at the termination of experiment. These results indicate that long-term stimulation of ACTH promotes the development of adrenocortical tumors but suppresses the occurrence of adrenal peliosis in rats treated with 4HAQO.

Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 μg hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.

Urinary excretion of free glucocorticosteriods and testosterone in the Mongolian gerbil ( Meriones unguiculatus): Effects of long-acting corticotrophin and human gonadotrophin

1. 1. Methods for the quantitative collection of 24-hr urines of small laboratory animals and for the measurement of urinary free glucocorticosteroids and testosterone are described. 2. 2. Urinary glucocorticosteroids and testosterone were determined in 0.1–0.5 ml-aliquots of 1 100 diluted urines after kieselgur mini-column extraction. 3. 3. Excretion of glucocorticosteroids and testosterone in undisturbed Mongolian gerbils was 329 and 13 ng/day, respectively. 4. 4. Administration of long-acting (1–24)ACTH (20 IU/animal) increased glucocorticosteroid and testosterone excretion to about 2000 ng/day (glucocorticosteriods) and to about 30 ng/day (testosterone) over 3 days. 5. 5. In animals injected with 100 IU/animal HCG, testosterone excretion was elevated to about 35–50 ng/day over 3 days. 6. 6. As the results show, the measurement of urinary excretion of free glucocorticosteroids and testosterone is a relable index of adrenal-gonadal function in the Mongolian gerbil. 7. 7. Furthermore, in small laboratory animals, steroid measurements in 24-hr urines may be superior to determinations in plasma, since amounts of urinary steroid are relatively high and 24-hr urines can be collected over longer time periods without stressing the animals.

Factors controlling adrenal weight and corticosterone secretion in male rats as revealed by median eminence lesions and pharmacological alteration of prolactin secretion

To determine whether or not prolactin, as well as ACTH, was involved in the control of adrenal weight and steroid release, lesions in the median eminence which had previoulsy resulted in impaired steroid release and atrophy of the adrenal were placed in animals in which the plasma prolactin was allowed to rise as a result of the lesions or prevented from rising by the administration of the dopamine agonist, CB-154. As previously reported, as the severity of diabetes insipidus (DI) increased as a result of interruption of the supraoptico-hypophyseal tract, adrenal weight declined reaching a nadir at water intakes of approximately 100–150 ml/day. This was followed by a reversal of this trend and an increase in adrenal weight as water intakes increased further. These effects were not modified by CB-154 which was effective to lower the elevated prolactin levels in the animals. In general, adrenal weight correlated with levels of plasma corticosterone and progesterone. The ability of the animals to undergo compensatory adrenal hypertrophy was also impaired by median eminence lesions in the presence or absence of CB-154. Exceptional animals were encountered in which adrenal weight was high and yet plasma corticosterone was low. Treatment of hypophysectomized animals with long-acting ACTH plus maintenance doses of triiodothyronine prevented the adrenal atrophy characteristic of the hypophysectomized animal, thus confirming that ACTH is the most important hormone in the control of adrenal weight. Some role for prolactin is suggested by the fact that elevation of prolactin via the drinking of sulpiride, a dopamine receptor blocker, was associated with a relatively small elevation of adrenal weight and plasma corticosterone. In the animals with lesions, blockade of adrenal function was always found in animals with complete lesions of the median eminence and was usually found if the lesion destroyed the anterior median eminence and extended caudally to the separation of the pituitary stalk. Lesions of the paraventricular nucleus did not block adrenal function, presumably because sufficient CRF neurons were located outside this structure to maintain adrenal function and/or because of the maintenance of considerable vasopressin secretion. Defective adrenal function was usually associated with DI indicative of interruption of the supraoptico-hypophyseal tract and deficient vasopressin secretion; however, several animals were found which had relatively high degrees of DI and yet adrenal function was relatively normal suggesting that CRF is more important than vasopressin in the control of ACTH secretion. Since some animals had relatively normal adrenal function and weight in the presence of severe damage to the median eminence it is possible that other pituitary factors, the release of which would be increased by such lesions, such as α-MSH, may play a role in maintenance of adrenal weight. The possible participation of neural factors also cannot be ruled out.

Studies on the mechanism of corticotrophin-mediated desensitization of corticosterone secretion by rat adrenocortical cells

Long-term exposure of the adrenocortical cells in vivo or in vitro to high concentrations of ACTH results in a diminution of the responsiveness of these cells to a subsequent stimulation of corticosterone release by ACTH. Conflicting studies have been published on the mechanism of this ‘desensitization’ phenomenon. Dispersed adrenocortical cells prepared from the hypertrophic/hyperplastic adrenal glands of rats bearing the ACTH/PRL-secreting rat pituitary tumour 7315a showed an increased basal release of corticosterone, but had lost their ability to respond further to ACTH. However, corticosterone release in response to dibutyryl cyclic AMP (dbcAMP), cholera toxin and forskolin remained intact. Pretreatment of normal rats for 3, 9 and 21 days with 50 μg/rat/day of a long-acting ACTH 1–24 depot preparation induced a dose-dependent increase in basal corticosterone release by the adrenocortical cells prepared from these animals and a dose-dependent decrease in the sensitivity to ACTH. However, the responsiveness of the adrenocortical cells prepared from the adrenal glands of control and ACTH 1–24 pretreatment rats to dbcAMP, cholera toxin and forskolin was similar. In addition, pretreatment with ACTH in vivo did not affect the sensitivity of the adrenocortical cells in vitro to calmodulin inhibition by haloperidol and 11β-hydroxylase inhibition by etomidate. It is concluded that long-term exposure of the adrenal gland to high concentrations of ACTH in vitro results in an excessive activation of corticosterone release by the adrenocortical cells in vitro, which is accompanied by a loss of sensitivity to ACTH. The sensitivity of these cells to cholera toxin and forskolin remains unchanged. The mechanism which might explain these phenomena includes down-regulation of the ACTH receptors or uncoupling of the ACTH receptor complex from the N s subunit.

Corticosteroids and lung surfactant levels in adult male rats

Following lung instillation in adult male rats of 3.4 μmol hexavalent chromium (K 2Cr 2O 7) dissolved in 0.5 ml of 0.9% NaCl, increased levels of lung surfactant could be detected after 48 h. The blood serum concentration of corticosterone was elevated in these animals. Blood serum thyroxine and triiodothyronine showed an initial increase after lung instillation of hexavalent chromium followed by a decline. Metabolism of testosterone by the alveolar macrophages to 17β-hydroxy-5α-androstane-3-one and 5α-androstane-3α,17β-diol was reduced 6 and 12 h after the K 2Cr 2O 7 instillation, which was also associated with damage of lung cell function and decreased uptake by the alveolar macrophages of Candida albicans particles. As early as 12 h after s.c. administration of 400 μg dexamethasone/100g body wt, increased levels of lung surfactant could be measured. At this time the lungs showed no signs of cellular damage, and metabolism of testosterone as well as uptake of Candida albicans particles by the alveolar macrophages were normal. Lower s.c. doses of dexamethasone did not result in raising the levels of lung surfactant in 12 h. Within 12 h after s.c. administration of large doses of testosterone, dihydrotestosterone or dehydroepiandrosterone no measurable effects on the levels of lung surfactant could be measured. Since animals treated with dexamethasone (200 μg/100 g body wt) or long-acting synthetic ACTH (100 μg i.m. Synacthen Depot/100g body wt) for 5 days after lung instillation of K 2Cr 2O 7 had extremely high levels of lung surfactant, it is concluded that the corticosteroids in adult rats may help to create augmented surfactant levels following lung intoxication. This could proceed via stimulation of surfactant production and reduction of surfactant removal. Different aspects of lung surfactant metabolism are discussed.

Hormonal regulation of ascorbic acid in the adrenal of the rat.

Fifteen days after hypophysectomy of rats the concentrations of ascorbic acid (AA) in adrenals, liver, blood and urine are lower than in normal rats or in rats 1 day after hypophysectomy. Despite the low levels the percentage AA depletion after administration of ACTH and the subsequent repletion to the pre-ACTH level are normal. Lack of corticosteroids is not the cause of the low AA levels, as shown by experiments in 15 days adrenalectomized rats and in rats treated with low doses of dexamethasone. Fifteen days treatment with high doses of dexamethasone lowered the AA concentrations in adrenals, liver and blood. Treatment with long-acting ACTH maintained adrenal weight but not adrenal and blood AA. A high dose of ACTH lowered these levels. The administration of AA markedly increased the AA levels in blood, but did not normalize its concentration in the adrenals, not even when the size of the adrenals was maintained by treatment with long-acting ACTH. Growth hormone, in particular when administered together with long-acting ACTH, markedly raised the AA concentration in the adrenals but hardly affected the AA blood level. Rats with high blood levels of prolactin induced by pituitary grafts in the kidney also had clearly higher AA levels in adrenals, but not in blood. These results indicate that, although acute AA release from the adrenal is caused by ACTH, AA uptake to a certain concentration is not controlled by the pituitary gland, and above this concentration is promoted by growth hormone and prolactin. In the liver AA release may also be caused by ACTH but the AA production is promoted by other as yet unidentified pituitary factors.

Adrenal androgens are highly stimulated during ACTH therapy for infantile spasms

Adrenocortical steroid secretion was studied in 10 infants (mean age 8.9 months, range 5-22 months) during and after ACTH therapy for infantile spasms. Long-acting ACTH (Acortan prolongR., Ferring, Sweden) was given i.m. once daily, 80 units during the first 3 weeks, 40 units during the following 2 weeks with tapering and termination within the next week. Serum dehydroepiandrosterone (DHA), androstenedione (A) and cortisol (F), and 24 h urinary cortisol (dUF) and 17-ketogenic steroids (KGS) were measured before, during (serum samples 24 h after the last ACTH dose) and after therapy (means and range nmol/1 for serum steroids, nmol for dUF and umol for KGS): Highly elevated androgen levels (up to adult values) show that ACTH is capable of causing adrenarchal changes in androgen secretion. Interestingly, after ACTH therapy there was no suppression of androgens below the pretreatment level in contrast to glucocorticoids. What causes adrenarche may not be a separate adrenal androgen stimulating hormone, but ACTH which gradually increases adrenal androgen secretion.

Metabolism in vitro of testosterone (T) to 17β-hydroxy-5α-androstane-3-one (DHT) and 5α-androstane-3α,17β-diol (3α) by the 800 g supernatant fraction of ileum from rats

The 800 g supernatant fraction of ileum from rats was incubated with testosterone and production of 17β-hydroxy-5α-androstane-3-one and 5α-androstane-3α,17β-diol measured. No difference in this production could be determined between ileum from mature female and mature male animals. Ileum from immature rats staying with their mothers from day 12 to day 21 showed increased 5α-reduction of testosterone on days 15, 17 and 21. Ileal metabolism to 17β-hydroxy-5α-androstane-3-one and 5α-androstane-3α,17β-diol was increased in immature animals on day 25 of extrauterine life when consuming rat chow and water ad libitum from day 21. This increase could not be demonstrated on day 28. Immature and mature animals treated either with long-acting ACTH or dexamethasone showed increased ileal conversion of testosterone to the two 5α-reduced metabolites determined. Ileum from mature male rats injected, subcutaneously, with arabinosylcytosine every 8th h for 2 days exhibited increased metabolism of testosterone to 17β-hydroxy-5α-androstane-3-one and 5α-androstane-3α,17β-diol from the 1st to the 6th day after the last injection of arabinosylcytosine. Different aspects of intestinal metabolism of testosterone are discussed.

In vitro metabolism of testosterone to 17ß-hydroxy-5α-androstane-3-one and 5α-androstane-3α, 17ß-diol by the rat intestine

The metabolism of testosterone to 17ß-hydroxy-5α-androstane-3-one and 5α-androstane-3α, 17ß-diol by the 800 g supernatant fraction by different parts of the gastrointestinal tract from male rats was investigated. This metabolism tended to be higher in immature than in mature animals. Administration of dexamethasone or long-acting ACTH to immature and mature rats increased testosterone metabolism to 17ß-hydroxy-5α-androstane-3-one and 5α-androstane-3α, 17ß-diol by ileum tissue. No such effect could be observed following administration of progesterone, estradiol, prolactin, LH or FSH in mature animals. Development of the gastrointestinal tract from the immature to themmature stage was associated with augmented metabolism of testosterone to 17ß-hydroxy-5α-androstane-3-one and 5α-androstane-3α,17ß-diol in the ileum.

Participation of glucocorticoids in the regulation of plasma LH levels in the male domestic duck (Anas platyrhynchos L.).

Adult male domestic ducks were treated in autumn for 14 consecutive days with either (i) long-acting ACTH (20 IU/day), (ii) corticosterone (25 mg/day), (iii) dexamethasone (0.25 mg/day) or (iv) a control solution. Blood samples were obtained from all birds after 1, 3, 7 and 14 injections of hormones; on each of these occasions, a sample was obtained 3 times during the day. The 3 hormonal treatments induced a marked and transient (observed on the 3rd and 7th, but not on the 1st and 14th days of injection) elevation of the LH plasma levels. This increase was not associated with any alteration of the testosterone plasma levels. The results are discussed in view of our knowledge of the influence of adrenal hormones on the pituitary-gonadal axis.

ACTH-elicited sodium appetite in sheep.

Intramuscular injections of long-acting synthetic ACTH (45 U twice daily for 5 days) caused a large increase in the intake of 0.5 M NaCl in sheep. Mean Na intake of the sheep on the last 3 days of treatment approximated 50% of their total extracellular fluid Na. The mineral appetite was specific for NaCl. Intakes of 0.5 M KCl or 0.25 M CaCl2 were not significantly altered. The enhanced appetite for Na induced by ACTH appeared to precede any increase in urinary Na excretion. ACTH treatment was ineffective in adrenalectomized sheep. However, an infusion into adrenalectomized sheep of a combination of adrenal steroid hormones (including aldosterone, deoxycorticosterone, 11-deoxycortisol, cortisol, and corticosterone) that contrived blood levels similar to those, obtained with ACTH treatment in normal sheep did induce Na appetite. Thus, ACTH induces a specific, adrenal-steroid hormone-dependent Na appetite in sheep.

Endocrine effects of castration followed by androgen replacement and ACTH injections in the male domestic duck ( Anas platyrhynchos L.)

Adult male ducks submitted to natural lighting were bilaterally castrated in the winter. They were then repeatedly injected as follows: testosterone propionate (= TP; 5 mg/day and male) + long-acting ACTH (20 IU/day and male): N = 6; TP + saline: N = 6; oil + ACTH: N = 5; finally oil + saline: N = 4. Blood samples of these birds were individually assayed at different times following the start of the treatments for LH, FSH, and corticosterone. Three days following castration, LH as well as FSH levels were significantly above the levels in a sham-operated group. By that time LH levels had increased significantly more than FSH levels, a difference which disappeared later on in the experiment. TP administration caused gonadotrophins to fall below values of sham-operated birds. This drop was much more important for LH than for FSH. ACTH treatment, while inducing important and time-dependent variations in the corticosterone levels, did not affect either LH or FSH levels. Measurement of gonadotrophins three times during the day did not enable the demonstration of daily variations in any group.