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PubMed1988

ACTH increases noradrenaline release in the rabbit heart.

The effects of ACTH on the release of noradrenaline and the increase of heart rate produced by sympathetic nerve stimulation (1 Hz) were studied in isolated perfused rabbit hearts. ACTH-(1-24) 0.1-100 nmol/l increased the stimulation-evoked overflow of noradrenaline concentration-dependently, reversibly and up to two-fold. The basal outflow of noradrenaline, the basal heart rate and the stimulation-evoked increase in heart rate were not changed. Human ACTH-(1-39) also increased the evoked overflow of noradrenaline. The effect of ACTH-(1-24) 0.3 nmol/l persisted after blockade of beta-adrenoceptors with propranolol and blockade of neuronal catecholamine uptake by cocaine. ACTH-(1-24) 3 nmol/l did not change the removal of noradrenaline from the perfusion fluid, when hearts were perfused with medium containing 59 nmol/l noradrenaline. The results show that ACTH increases the action potential-evoked release of noradrenaline from cardiac postganglionic sympathetic neurones, probably by activating specific presynaptic ACTH receptors. The high potency of ACTH suggests that these presynaptic receptors may be activated in vivo by circulating ACTH under certain pathophysiological conditions.

Animals↗
PubMedDate not supplied

The role of vasopressin in the nicotine-induced stimulation of ACTH and cortisol in men.

Experimental evidence indicates that arginine vasopressin (AVP) contributes to the release of ACTH under certain conditions. The present study investigates the role of vasopressin as a secretagogue of ACTH during cigarette smoking or nicotine infusion with additional injection of corticotropin releasing hormone (CRH) and using the specific AVP antagonist d(CH2)5Tyr(Me)-AVP. We first tested the effect of the AVP antagonist (10 micrograms/kg body weight i.v.) on ACTH and cortisol release following cigarette smoking in 15 healthy young male smokers. Smoking led to marked increments in plasma nicotine and to a small rise in plasma ACTH and cortisol. Mean plasma ACTH and cortisol levels were at no time significantly altered by the antagonist. This might be due to a slight agonistic effect of the AVP antagonist, to high interindividual variability of the ACTH and cortisol responses after smoking or to a negligible role of AVP in smoking-induced ACTH release. In a second study we performed the following tests in six healthy male non-smokers: (1) nicotine infusion (1.0 micrograms/kg body weight per min); (2) CRH i.v. (100 micrograms); (3) AVP antagonist i.v. (5 micrograms/kg); (4) nicotine infusion plus CRH i.v.; (5) nicotine infusion plus AVP antagonist i.v.; (6) nicotine infusion plus CRH and AVP antagonist i.v.; and (7) sham infusion. Nicotine infusion led to greater increments of AVP, ACTH and cortisol than smoking without causing nausea. Peak nicotine levels after nicotine infusion were lower than after smoking. The AVP antagonist in the reduced dosage given alone had no effect on hormone levels. However, it slightly attenuated the effect of nicotine on ACTH and cortisol (P less than 0.05, ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Immunocytochemical characterization of mouse monoclonal ACTH antibodies with a note on staining conditions and control procedures.

Mouse monoclonal antibodies (MAbs) have been produced against porcine ACTH and tested for their immunocytochemical utility. Ten out of 12 MAbs reacted with formaldehyde-fixed human ACTH[1-39] and fragments thereof. Cytochemical fragment testing revealed that 6 of the 10 MAbs recognized epitopes in the vicinity of the region where porcine ACTH differs from mouse ACTH (amino acids 26, 29 and 31). Both tissue and cytochemical model data indicate that many of the MAbs detected porcine ACTH with somewhat higher potency than human and rat ACTH (rat ACTH[1-39] is identical to mouse ACTH[1-39]). MAbs Nos. 5, 8 and 12, in particular, revealed a highly satisfactory signal to noise ratio also in formalin-fixed, paraffin-embedded specimens. Most of the MAbs were potent in detecting both the high concentrations of ACTH congeners in corticotrophs and melanotrophs and the lower concentrations of such peptides in human antropyloric gastrin cells. Blocking of tissue endogenous peroxidase activity reduced reactivity towards the MAbs. This could be circumvented by use of biotinylated primary antibodies combined with avidin/streptavidin-alkaline phosphatase detection. Availability of MAbs and of the corresponding synthetic antigen also made some quantitative comparisons and analyses of appropriate control procedures possible.

Adrenocorticotropic Hormone↗
PubMed1990

ACTH-induced behaviors and their modulation by serotonergic agonists differ in neonatal and weanling rat pups.

Four-day-old (P4) and 21-22-day-old (P21-22) rat pups received an intracisternal injection of either ACTH1-16NH2 or saline followed by a subcutaneous (SC) injection of saline, the serotonergic (5HT)1A agonists 8-OH-DPAT or ipsapirone, the 5HT1B agonist TFMPP or the 5HT2 agonist DOI. The ontogeny of ACTH-induced behaviors including grooming, yawn and stretch as well as various serotonin-related behaviors were recorded via time-sampling at 20 s intervals for a test duration of 50 min. ACTH induced slight but significant increases in grooming at P4, along with a significant increase in yawning. At this age the 5HT1B agonist TFMPP induced substantial increases in grooming, with no effect of the other agonists on this behavior. All of the serotonergic agonists, however, decreased ACTH-induced yawning at P4. At P21-22 ACTH induced more robust grooming than that observed at P4, although different in nature from adult-typical ACTH-induced grooming. This ACTH-induced grooming at P21-22 was attenuated by all of the serotonergic agonists. ACTH-induced yawning at P21-22 was not affected by the serotonergic agonists while ACTH-induced stretching was increased by the 5HT1B agonist TFMPP at this age. These data provide additional evidence of differential mediation of various ACTH-induced behaviors, and support other reports of ontogenetic alterations in the response to serotonergic manipulations during the neonatal to weanling age period.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

ACTH 1-17 and pituitary-adrenal function in human.

In this study we have compared the effects of the ACTH 1-17 analogue, alsactide (Synchrodyn 1-17,) and of the ACTH 1-24 fragment, on the dynamics of ACTH-cortisol secretion. In 2 healthy women, 100 micrograms alsactide injected i.m. at 07(00) caused a much greater and sustained cortisol secretion than 100 micrograms ACTH 1-24. However, adrenocortical stimulation effected by alsactide terminated within 24 h, since plasma cortisol levels recorded 24 h after alsactide injection were even lower than the corresponding values of the previous day. In 8 other women, daily administration of 100 micrograms alsactide at 07(00) for 15-days resulted in a significant blunting (p less than 0.05) of the ACTH secretion in response to insulin-induced hypoglycemia. This finding is even more meaningful in view of the more marked blood glucose fall (p less than 0.01) observed in the post treatment insulin tolerance test. Both baseline and insulin-stimulated cortisol levels were reduced after alsactide (p less than 0.02) so that cortisol increments above baseline were of comparable magnitude before and after treatment with the ACTH analogue. In 8 additional women, no significant changes in the cortisol response to hypoglycemia, in spite of more profound blood glucose fall (p less than 0.05), were noted after a 15-day treatment with 250 micrograms ACTH 1-24 daily. In all, these findings show that ACTH 1-17, compared to ACTH 1-24, effects a much more potent stimulation of cortisol secretion which, however, terminates within 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed2007

Immunohistochemical Jun/Fos protein localization and DNA synthesis in rat adrenal cortex after treatment with ACTH or FGF2.

In vitro and in vivo studies have suggested that the expression of the early response genes for Jun and Fos proteins plays an important role in adrenal cell proliferation. In order to study the expression pattern of the activating protein-1 (AP-1) family of oncogenes in the adrenal gland, we have used immunohistochemistry to localize Jun and Fos protein expression in rat adrenal cortex infused in situ with adrenocorticotropic hormone (ACTH), fibroblast growth factor 2 (FGF2), or both. The expression of AP-1 factors has been found to be correlated with in vivo ACTH and FGF2 proliferation in rats treated with dexamethasone and bromodeoxyuridine (BrdU). Induction of c-Jun and c-Fos in the zona fasciculata and of FosB in the zona reticularis suggests that, after ACTH stimulation, these proteins are the main AP-1 components in these zones. In vivo, ACTH increases BrdU-positive cells in the zona fasciculata and zona reticularis suggesting that the composition of AP-1 complexes in these zones is correlated with proliferation. Patterns of Fos and Jun induction by FGF2 do not resemble those after ACTH induction. However, in isolation, neither affects the zona glomerulosa. In the zona fasciculata, and more so in the zona reticularis, FGF2 modulates responses to ACTH, reducing the numbers of Jun-positive cells, Fos-positive cells, and DNA synthesis. This indicates that FGF2 antagonizes ACTH, and that ACTH thus controls the trophic effect independently of exogenous FGF2. Our results implicate the AP-1 family of transcription factors in the regulation of cell progression and the control of ACTH-induced proliferation in the zona fasciculata and zona reticularis.

Adrenal Cortex↗
PubMed1987

Oxytocin reduces metyrapone-induced ACTH secretion in human subjects.

The inhibitory action of oxytocin (OT) on adrenocorticotropin (ACTH) secretion has been disputed. Thus we evaluated the effect of exogenous OT on the elevated blood ACTH levels in normal human subjects. Metyrapone, a blocker of cortisol secretion, was given to enhance ACTH release. This experimental model was chosen because metyrapone-induced ACTH activation depends on diminution of the negative feed-back of cortisol, which is an important physiological mechanism in the control of ACTH secretion. A striking decline in plasma cortisol levels and a 10-fold rise in the mean plasma ACTH concentration was observed within 20 h after the beginning of metyrapone treatment (750 mg orally every 4 h). The administration of OT (2 IU as a i.v. bolus plus 4 IU infused in 2 h) significantly reduced the metyrapone-induced plasma ACTH rise. Since the effect of OT was evident when ACTH secretion was enhanced by a reduced cortisol-dependent negative feed-back, confirmation of the inhibitory action of OT on the ACTH secretory system in man is provided.

Adrenocorticotropic Hormone↗
PubMed1987

Characterization of PGE2 inhibition of corticotropin releasing factor-mediated ACTH release.

The role of prostaglandin E2 (PGE2) on the mechanism of corticotropin releasing factor (CRF) induced adrenocorticotropin (ACTH) release was studied in primary rat pituitary cell culture. The continuous incubation of pituitary cells with PGE2 inhibited CRF-stimulated ACTH with an ED50 of 1.2 X 10(-9) M PGE2. PGE2, however, did not alter the spontaneous release of ACTH. PGE (10(-8) M) significantly decreased 10(-10) M, 10(-9) M, and 10(-8) M CRF-mediated ACTH release by 42%, 47%, and 31% of total CRF stimulated ACTH release. Time course experiments demonstrated a PGE2-induced inhibition by 20 min of CRF incubation which continued for 3 h. After a 2-h incubation with PGE2, the wash-out of PGE2 from the culture medium just prior to the addition of CRF eliminated the inhibitory activity of PGE2. PGE2 decreased the amount of CRF-stimulated ACTH from cells incubated with cycloheximide (P less than 0.01). The inhibitory activity of PGE2 (10(-8) M) on CRF-stimulated ACTH was unaltered by the addition of 3 mM or 7 mM CaCl2 to the standard culture media (1.6 mM CaCl2). The inhibition of CRF-induced ACTH release by maximal inhibitory concentrations of PGE2 (10(-7) M) and cortisol (5 X 10(-7) M) were not additive. In conclusion, PGE2 may play an important role in modulating pituitary ACTH release. Its inhibitory activity occurs by 20 min of CRF incubation, is in part independent of protein synthesis, requires the continued presence of PGE2, is not reversed with CaCl2, and is not additive with the inhibitory activity of cortisol.

Adrenocorticotropic Hormone↗
PubMed1987

ACTH increases noradrenaline release in pithed rabbits with electrically stimulated sympathetic outflow.

ACTH 0.03-1 microgram/kg per min i.v. increased the noradrenaline spillover rate (the rate at which endogenous noradrenaline enters into plasma) and the plasma noradrenaline concentration in pithed rabbits with electrically stimulated sympathetic outflow. ACTH 0.1 and 1 microgram/kg per min decreased the mean arterial pressure (MAP). The effects of ACTH persisted in animals treated with propranolol. Corticosterone 10 micrograms/kg per min had no effect on the neurochemical and circulatory parameters. ACTH 0.03 and 1 microgram/kg per min increased plasma corticosterone and cortisol concentrations; the two doses of ACTH had approximately the same effect. The plasma corticosterone concentration reached after infusion of corticosterone 10 micrograms/kg per min was about twice that obtained after ACTH 0.03 or 1 microgram/kg per min. In a second series of experiments, a pressor dose of noradrenaline (1 or 2 micrograms/kg per min) was infused i.v. into pithed rabbits. ACTH 0.03 and 1 microgram/kg per min decreased blood pressure and increased heart rate in these animals. The results suggest that high doses of ACTH increase noradrenaline release by an action on postganglionic sympathetic neurons. The effect is probably not mediated through adrenal steroids. In addition, ACTH seems to decrease MAP and to increase heart rate through postsynaptic vascular and myocardial effects.

Adrenocorticotropic Hormone↗
PubMed1986

In vitro study of frog (Rana ridibunda Pallas) interrenal function by use of a simplified perifusion system. VIII. Structure-activity relationship of synthetic ACTH fragments and gamma-MSH.

The present study was undertaken to determine the structure-activity relationships of ACTH analogs on corticosteroid production by frog adrenal gland. Rana ridibunda interrenal dice were perifused with amphibian culture medium for 10 hr. Corticosterone and aldosterone concentrations were measured in the effluent perifusate using sensitive and specific radioimmunoassay methods. Perifusion of interrenal fragments with increasing concentrations of synthetic human ACTH 1-39 (ranging from 6.25 X 10(-11) to 10(-9) M) led to a linear log-dose increase in both corticosterone and aldosterone secretion. Thus, this model made it possible to compare the steroidogenic potency of several ACTH analogs. Synthetic alpha-MSH and its des-N alpha-acetyl derivative were found to be approximately equipotent, and 5 X 10(3) times less active than authentic ACTH. The short-chain analog ACTH 1-10 was 2 X 10(4) times less potent than ACTH whereas ACTH 4-10 was totally inactive. A fragment of the N-terminal region of the proopiomelanocortin molecule, gamma 3-MSH, caused a dose-related stimulation of steroid secretion. However, in contrast to what has been observed in the rat, gamma 3-MSH did not potentiate the corticotropic action of ACTH on frog interrenal gland. Since processing of proopiomelanocortin in frog intermediate lobe generates high amounts of alpha-MSH and des-N alpha-acetyl alpha-MSH, these results suggest that in amphibians, several peptides other than ACTH may be involved in the control of corticosteroidogenesis.

Adrenal Glands↗
PubMed1992

Effects of mammalian ACTH on potential fuels and gluconeogenic substrates in the plasma of the spiny dogfish shark (Squalus acanthias).

The effects of mammalian ACTH on plasma beta-hydroxybutyrate, glucose, alanine, and lactate levels were determined in the unfed spiny dogfish shark (Squalus acanthias). Serial blood samples were collected from a cannula implanted in the dorsal aorta. The metabolite levels were estimated by standard enzymatic procedures for 4 days before treatment and for 4 days after treatment. Plasma glucose, alanine, and lactate, but not beta-hydroxybutyrate, declined after the surgery, but the metabolites were relatively stable for at least 48 hr before treatment. ACTH (40 units/kg) or the control solution were infused via the cannula after the morning blood sample on postoperative Day 4 and again after the 12-hr blood sample. Control plasma beta-hydroxybutyrate, glucose, and lactate did not change significantly, but alanine levels increased approximately 29% by 96 hr when sampling ended. Plasma beta-hydroxybutyrate levels were not significantly changed by ACTH treatment. Plasma glucose levels increased approximately 36% by 3 hr after ACTH infusion, remained elevated following the second ACTH treatment, and then declined to approximately the initial levels by 96 hr. Plasma alanine levels increased approximately 53% by 0.75 hr after ACTH treatment, were still approximately 15% greater than the initial levels by 12 hr, rose again after the second ACTH infusion at 12 hr, and then declined to near the control levels by 96 hr. Plasma lactate levels increased approximately 107% by 1.5 hr after ACTH infusion and then decreased to approximately 22% greater than the initial levels by 12 hr. Lactate levels increased after the second ACTH infusion and remained approximately 58% greater than the initial levels when sampling ended at 96 hr. The results indicate that the pituitary-adrenocortical axis hormones do not directly influence plasma beta-hydroxybutyrate levels. However, the data support the suggestion that the hyperglycemic action of the pituitary-adrenocortical axis hormones is mediated, at least in part, by the provision of alanine and lactate substrates for gluconeogenesis.

3-Hydroxybutyric Acid↗
PubMed1981

Effect of ACTH infusion on induction of uterine contraction in prolonged human pregnancy in association with endocrine function.

The role of hormonal interactions in the mechanism initiating labor in women was studied. The serum levels in women was studied. The serum levels of cortisol, progesterone, estradiol estriol, human chorionic somatomammotropin, and prolactin were measured simultaneously before, during and after infusion of ACTH at a rate of 50 microgram/h in 100 ml of physiological saline or infusion of physiological saline without ACTH (as control) at a rate of 100 ml/h into 14 pregnant women of 10 days or more beyond term. In five (group A) of the 10 women infused with ACTH. uterine contractions were induced within 5-15 min after beginning of ACTH infusion. Although the serum progesterone levels in group A were slightly, but not significantly, lower than those in the other five women (group B) in whom uterine contractions were not induced, the ratio of progesterone to estriol was 13/1 in group A and 18/1 in group B, respectively (P less than 0.05). The endocrine levels in group A may be favorable for the initiation of uterine contraction. The serum cortisol levels in group A were higher, but not significantly higher, than those in group B after ACTH infusion. And the serum estriol levels 6 h after ACTH infusion were significantly lower than control levels before ACTH infusion (P less than 0.01 in group A, P less than 0.05 in group B). To the contrast, in all the four control women infused with physiological saline only (group C), neither uterine contractions nor changes in the serum levels of ACTH and cortisol were found. This work may show that ACTH infusion induced uterine contractions by increased corticosteroids via placenta in lower ratio of progesterone to estrogen but it does not provide any precise information on the mechanism of initiation of human labor.

Adrenocorticotropic Hormone↗
PubMed1993

Cerebrospinal fluid corticotropin-releasing hormone and ACTH, and peripherally circulating choline-containing phospholipid in senile dementia.

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, plasma levels of ACTH and cortisol, and serum levels of phospholipid and its fractions were determined in samples taken simultaneously from patients with senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID) or dementia following a cerebrovascular accident (CVD), and the borderline-to-normal control subjects. CRH levels in CSF were significantly reduced in patients with SDAT and CVD but not with MID compared to the borderline-to-normal controls. ACTH levels in CSF were significantly reduced in SDAT compared to MID. The levels of circulating lecithin (phosphatidyl-choline) were depressed in a similar fashion to the levels of CRH in CSF in the SDAT patients and the group of severe dementia. Dementia and its severity did not affect the morning plasma levels of ACTH and cortisol. CSF CRH was positively correlated with CSF ACTH, while CSF ACTH was negatively correlated with plasma cortisol. No significant correlations were found between serum lecithin and CSF CRH or ACTH. These findings suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) the CRH system and the ACTH system correlate with each other within the brain; 3) CSF ACTH is subject to the feedback inhibition by circulating cortisol; and 4) in the SDAT patients and the severe dementia group CSF CRH and serum lecithin are reduced probably via independent mechanisms.

Adrenocorticotropic Hormone↗
PubMed1976

Steroidogenic responses to varying parenteral routes of administered (alpha 1-18) ACTH.

In healthy human subjects, the steroidogenic responses to a single injection of alpha 1-18 ACTH by the subcutaneous, intramuscular, and intravenous (IV) routes were assessed by measurement of plasma cortisol levels, 17-hydroxycorticosteroid excretion, and cortisol secretion rates. Results showed that regardless of the parenteral route used, alpha 1-18 ACTH at doses of 1.0 and 0.5 mg was an effective adrenocorticotropic agent; however, with the IV route, the effect was considerably prolonged. The patterns of disappearance within the plasma of alpha 1-18 ACTH and alpha 1-24 ACTH were compared following a single IV injection of these compounds labeled with 125I. ALPHa 1-18 acth produced only a slight initial rise and a slower decline in plasma radioactivity compared to alpha 1-24 ACTH, suggesting slower degradation of alpha 1-18 ACTH. Administered as a single IV injection, alpha 1-18 ACTH has a prolonged effect on steroidogenesis and has potential for being a useful diagnostic and therapeutic ACTH preparation.

17-Hydroxycorticosteroids↗
PubMed1987

Previous chronic ACTH administration does not protect against the effects of acute or chronic stress in male rats.

The effect of previous chronic ACTH administration on the physiological response to acute and chronic immobilization stress was studied in adult male rats. Chronic ACTH administration slightly reduced food intake and drastically inhibited body weight gain. Serum corticosterone levels were similar in saline- and ACTH-treated rats twenty hours after the last administration. However, the corticosterone response to 1 hr immobilization was greatly reduced by previous ACTH administration. When the exposure to the stressor was prolonged up to 18 hours, the corticosterone response was similar in saline, and ACTH-treated rats. While body weight loss caused by starvation and acute stress was lower in ACTH-treated rats, stomach ulceration was greater in the latter animals. Although ACTH-treated rats showed higher body weight gain than saline-treated animals during chronic immobilization, this was probably due to catch-up growth as food intake inhibition caused by the stressor was similar in the two groups. Pituitary-adrenal adaptation to the repeated stressor was the same in saline- and ACTH-treated rats. Therefore, the effects of previous ACTH treated on the physiological response to either acute or chronic stress appear to be mixed, depending on the variable studied.

Adrenal Glands↗
PubMed1991

Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration.

The laboratory rat was used as a model to investigate the effect of pre- and/or postnatal ACTH administration on sexual differentiation of the brain. Pregnant Sprague-Dawley rats were injected with ACTH 1-24 (10 micrograms/kg/2x/day or 500 micrograms/kg/2x/day); postnatally treated neonates were injected with the above dosages once a day. Perinatal treatment with ACTH (10 micrograms/kg/2x/day) altered several sexual behavior measurements, but did not have an overall effect on the number of males that exhibited sexual behavior. At a higher dose (500 micrograms/kg/2x/day) prenatal ACTH administration decreased sexual behavior in male rats, as measured by an increase in the percent of males that did not mount or intromit. In contrast, all males treated postnatally with ACTH (500 micrograms/kg/2x/day) completed 2 ejaculatory series and initiated a third series. No significant differences were observed in adult plasma testosterone or prolactin levels; however, serotonin levels in the preoptic area of adult male rats treated prenatally with ACTH (500 micrograms/kg/2x/day) were significantly higher than in prenatally treated saline males. In addition, an increase in plasma ACTH in adulthood was observed in animals injected postnatally with saline. This study indicates that the decrease in sexual behavior observed in males treated prenatally with ACTH is associated with increased serotonin levels in the preoptic area, which suggests that ACTH may act as a neuromodulator during sexual differentiation of the brain. It also demonstrates that the effect of perinatal manipulations on the development of male sexual behavior may vary depending on the ontogenetic period of the brain.

Adrenocorticotropic Hormone↗
PubMed1983

The reversibility of the effects of ACTH and cytochalasin B on the ultrastructure and steroidogenic activity of adrenocortical tumor cells in vitro.

We have demonstrated previously that the steroidogenic activity of ACTH on cultured adrenal tumor cells is associated with cell rounding and a rearrangement of microfilaments. Cytochalasin B (CB) also induces cell rounding, but changes the conformation of microfilaments and severely inhibits steroidogenesis. ACTH and CB may have different modes of action on the contractile machinery which are related to their opposing actions on steroidogenesis. To investigate this possibility further, we have examined the reversibility of the morphological and functional effects of these agents. Cultures were incubated for 1 hr, with and without ACTH (10 microU/ml of media), or with CB (50 micrograms/ml), or with both agents simultaneously. After a media wash, the cultures were incubated for 1 hr, with and without ACTH. The steroid production of the cells during pre- and post-washout incubations was determined, and some cultures were fixed for electron microscopy at the end of both incubation periods. The three- to ten-fold increases in steroidogenic activity of ACTH-stimulated cells declined during recovery incubations, but remained well above basal values. These cells nearly reflattened and began to regain stress fibers which had been 'pulled apart'. The 'washed out' ACTH-stimulated cells were often refractory to restimulation. Cells recovering from CB also reflattened. Masses of filamentous felt induced by the drug disappeared from the cytoplasm, lost microvilli reappeared and stress fibers reformed. The 20-50% inhibition of basal steroidogenesis by CB was completely reversed. When ex-CB-treated cells were incubated with ACTH, their morphology and steroid production were typical of acutely stimulated cells. The recovery behavior of cells incubated with ACTH and CB simultaneously reflected the observation that there were cell-specific responses to one agent or the other during initial incubations. The persistence of heightened steroidogenic activity following a washout of ACTH and the rapid reversal of the effects of CB strongly support the concept that regulated actomyosin interactions are an integral part of the steroidogenic process.

Actomyosin↗
PubMed1978

Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues.

Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response.

Adrenocorticotropic Hormone↗