Doses Of ACTH Research Articles

Ageing and the sensitivity of the adrenal gland to physiological doses of ACTH in man

Healthy men and women aged 19-38 or 67-83, in whom endogenous ACTH secretion was suppressed with dexamethasone, were given successive injections of 60 ng, 150 ng and 250 micrograms ACTH(1-24) at hourly intervals, and blood samples for measurement of plasma cortisol were taken every 10 min. The response to each injection was taken as the increase in cortisol concentration 20 min later, when there was a peak with the lower doses, with allowance for disappearance of cortisol produced after the previous injection. On average, the responses to 60 and 150 ng ACTH were about 0.4 and 0.7 respectively of the response to 250 micrograms. There were no consistent effects of age or sex on any index of adrenocortical sensitivity or responsiveness, but some groups showed isolated differences from both their age- and sex-matched counterparts: the response to 60 ng ACTH was low in young men, maximal responsiveness was low in elderly men and the slope of the dose-response curve was high in elderly women. In most of the elderly subjects, plasma ACTH was determined separately under normal conditions. It was negatively correlated with the cortisol responses to 60 and 150 ng ACTH, suggesting that differences in adrenal sensitivity between subjects contribute to the variability of plasma ACTH.

Insulin-like growth factor I (IGF I) induces cortisol production in bovine adrenocortical cells in primary culture

The effects of a physiological dose of IGF I (40 ng/ml approximately 5 x 10(-9) M) on steroidogenesis were studied in bovine adrenal fasciculata cells cultured in serum-free McCoy's medium. They were compared with those of a single dose of ACTH (0.25 ng/ml approximately 10(-10) M) at approximately the concentration inducing half-maximal stimulation. With IGF I, steroidogenesis commenced after 48 h culture and progressively increased throughout the 96-h test period. Expressed as stimulated level/control level ratios, glucocorticoid (cortisol + corticosterone) responses to IGF I after 4 days' culture (2.41 +/- 0.20 (SEM) n = 9) were similar to those obtained with ACTH (2.59 +/- 0.18, n = 9). A combination of the two peptides had a synergistic effect (5.95 +/- 0.79, n = 5). The cortisol/corticosterone ratio increased in the presence of IGF I from 1 +/- 0.19 to 1.76 +/- 0.45 (n = 7, P less than 0.02), although less so than in the presence of ACTH (5.50 +/- 0.98). Moreover, cortisol production was accompanied by androstenedione production (2.36 ng/10(6) cells, n = 3) similar to that induced by ACTH (2.10 ng/10(6) cells, n = 3). These findings together suggest stimulation of 17 alpha-hydroxylase activity. Cell multiplication was unaffected by IGF I. [3H]Thymidine incorporation into DNA reached only 193% +/- 17 (SEM) (n = 4) of control levels, whereas with ACTH it dropped to 60% +/- 5. Our findings show that IGF I alone has no mitogenic effect on adrenocortical cells in vitro, but that it is capable of inducing differentiated steroidogenesis.

ACTH therapy in infantile spasms: Relationship between dose of ACTH and initial effect or long-term prognosis

The relationship between the dose of ACTH and the initial effect was investigated in 41 children with infantile spasms. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and electroencephalographic abnormalities. The relationship between the dose of ACTH and long-term prognosis was investigated in 29 patients. There was no relationship between the daily or total ACTH dosage, provided the dose was > 0.015 mg (0.6 IU)/kg/day, and the outcome of seizures and electroencephalographic abnormalities; however, ACTH 0.04–0.06 mg (1.6–2.4 IU)/kg/day and a total ACTH dose of 1.1–1.5 mg (44–60 IU)/kg resulted in better mental development than smaller doses of ACTH. Side effects of ACTH increased with dosage. Too small or too large a dose of ACTH does not lead to better mental development. The proper dose of ACTH should be used with careful attention to potential side effects.

Insulin-induced hypoglycemia stimulates corticotropin-releasing factor and arginine vasopressin secretion into hypophysial portal blood of conscious, unrestrained rams.

Insulin-induced hypoglycemia (IIH) is a strong stimulator of pituitary ACTH secretion. The mechanisms by which IIH activates the corticotrophs are still controversial. Indeed, in rats the variations of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) secretion in hypophysial portal blood (HPB) during IIH have been diversely appreciated. This may be due to the stressful conditions required for portal blood collection in rats. We studied the effects of IIH on the secretion of CRF and AVP in HPB and on the release of ACTH and cortisol in peripheral plasma in conscious, unrestrained, castrated rams. After the injection of a low (0.2 IU/kg) or high dose (2 IU/kg) of insulin, ACTH and cortisol levels in peripheral plasma increased in a dose-related manner. After injection of the low dose of insulin, CRF and AVP secretion in HPB were equally stimulated. After injection of the high dose of insulin, CRF secretion was further stimulated, while AVP release was dramatically increased. These results suggest that when the hypoglycemia is moderate, CRF is the main factor triggering ACTH release, and that the increased AVP secretion potentiates the stimulatory effect of CRF. When hypoglycemia is deeper, AVP secretion becomes predominant and may by itself stimulate ACTH release.

Acute Adrenocorticotropin-(1–24) (ACTH) Adrenal Stimulation in Eumenorrheic Women: Reproducibility and Effect of ACTH Dose, Subject Weight, and Sampling Time*

Assessment of adrenal reserve and the diagnosis of adrenal insufficiency by acute adrenocortical stimulation with ACTH-(1-24) has been well established. Alternatively, estimation of adrenocortical enzymatic activities by this method for the detection of inherited or acquired biosynthetic abnormalities has been less well characterized. Some of the discrepancies between studies estimating adrenocortical enzymatic activities in different pathological conditions (e.g. hyperandrogenism) may result from the different stimulation protocols used. The objective of this prospective study was to establish the inherent variability of the adrenal response to acute ACTH-(1-24) stimulation and to determine the effect of sampling time, stimulation dose, and subject weight on the same. Forty-one normal female volunteers were recruited (mean age, 29.1 yr), 30 within 90-110% ideal body weight and 11 weighing more than 120% ideal body weight. Three protocols were designed to study 1) the effects of sampling time, ACTH-(1-24) dose, and subject weight on adrenal response; 2) the effect of time of the day on the variability of basal steroid levels and the adrenal response to stimulation; and 3) the long term reproducibility of the adrenal response to ACTH-(1-24). Androstenedione, 17-hydroxyprogesterone, 11-deoxycortisol, dehydroepiandrosterone, and cortisol were measured in serum under basal and stimulated conditions. All subjects had normal basal levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and PRL. The acute iv administration of 0.10, 0.25, and 1.0 mg ACTH-(1-24) elicited similar and maximal steroid responses, with all steroid levels reaching a plateau 60-90 min poststimulation regardless of subject weight. Sampling of basal steroid levels every 5 min in the morning (AM; beginning 0700-0900 h) or evening (PM; 1500-1700 h) did not reveal any difference in steroid variability. Only the mean basal cortisol level was higher in AM than PM testing (P less than 0.03). Although the mean levels of dehydroepiandrosterone and 17-hydroxyprogesterone 60 min after stimulation were significantly higher in AM than PM studies, these differences were minimal. Ten volunteers underwent an average of four (range, 2-6) adrenal stimulation studies using 1.0 mg ACTH-(1-24) over a 1-yr period. The long term coefficient of variation (CV) for basal steroid levels ranged from 15-28%. Calculations of net adrenal response (delta steroid O-T and area delta steroid O-T) were less reproducible (CV, 0-82%) than measures of absolute response (steroid T, area steroid T, and %steroid T; CV, 7-32%). This difference in CV between the measures of net and absolute adrenal responses was significant for all steroids except androstenedione.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocortical sensitivity to low-dose ACTH administration in depressed patients

We studied adrenocortical sensitivity to ACTH 1−24 in depressed patients after suppressing endogenous ACTH with dexamethasone. The dose of ACTH 1−24 used (50 ng) was based on prior studies showing that it produced a consistent response

Effect of ACTH on VIP and Galanin Release from the Pituitary*

The effect of adrenocorticotropin (ACTH) on the release of four regulatory peptides from the anterior pituitary of male rats has been studied using an in vitro perfusion system. Quartered anterior pituitaries from male adult Wistar rats were perfused with buffer containing different concentrations of ACTH and, subsequently, 56 mM KCl. Fractions of 1.5 ml were collected at 3 min intervals and analyzed for vasoactive intestinal peptide (VIP), galanin, 7B2, and substance P, using specific radioimmunoassays. Concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH produced increases of 117 +/- 50%, 155 +/- 90%, 163 +/- 14%, and 161 +/- 3% (mean + SE), respectively, of basal release of VIP (P less than 0.001). However, concentrations of 1 microM and 2 microM ACTH suppressed VIP release to 74 +/- 6% and 47 +/- 4%, respectively, compared to basal release (P less than 0.001). Results for galanin release were similar: concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH increased galanin release to 129 +/- 4%, 136 +/- 8%, 143 +/- 9%, and 133 +/- 9% of basal release (P less than 0.001) and 1 and 2 microM ACTH provoked a suppression of 52 +/- 7% and 50 +/- 13%, respectively, compared with basal release (P less than 0.001). Doses of ACTH that altered the secretion of VIP and galanin had no effect on 7B2 and substance P release. These results demonstrate that ACTH causes a release of pituitary VIP and galanin in vitro and, moreover, that this is a biphasic phenomenon.

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)

Plasma LH, FSH, testosterone, prolactin and androstenedione in male white-tailed deer after acth and dexamethasone administration

1. 1. In order to investigate the role of the adrenocortieal system in the regulation of plasma levels of reproductive hormones, adult male white-tailed deer (five intact and one castrated) from a captive herd were sedated with xylazine and ketamine and then challenged with various doses of ACTH with and without dexamethasone (DX) pretreatment. 2. 2. Plasma levels of LH, testosterone (T), FSH, prolactin (PRL) and androstenedione (A) were determined by RIA in serial samples taken from the jugular vein. 3. 3. An increase of A levels detected after ACTH in both intact and castrated deer indicated stimulation of secretion of adrenal androgens by ACTH. 4. 4. No effect on FSH and PRL levels was observed in either group. 5. 5. A significant decline of LH and T observed in various treatments could not be attributed to ACTH or DX administration. It is speculated that the decrease may be caused by anaesthetics which alleviate the stress induced in deer by the pre-immobilization activities.

Sex-dependent effect of melatonin on the secretory activity of rat and hamster adrenal gland [formula omitted

Adrenal quarters from adult male or female hamsters were incubated in the presence of melatonin (10 −7 or 10 −4 M), and cortisol concentration in the incubation medium was assayed by RIA. Melatonin did not change cortisol output by adrenals obtained from the male hamsters, while a slight stimulatory effect was observed in female glands, the lower concentration of melatonin being more effective than the higher one. At both concentrations tested, melatonin notably stimulated corticosterone output by isolated rat adrenocortical cells derived from the males, and lowered corticosterone secretion by the cells obtained from the female glands only at a concentration of 10 −7 M. The lower concentration of melatonin increased ACTH (0.1 mU. m1 −1) -stimulated corticosterone output by the cells of male and female rat adrenals. The pineal hormone was ineffective at a concentration of 10 −4 M, as well as in the presence of a higher dose of ACTH (1.0 mU.m1 −1). These findings indicate a distinct sex-dependent effect of melatonin on in vitro cortisol and corticosterone production, and demonstrate that the modulatory effect of melatonin of the secretion of steroid hormones is more effective at lower concentrations.

Research Note: Physiological Effects of Adrenocorticotropic Hormone and Hydrocortisone in Laying Hens

To study the hormonal effects on hematologic parameters as indicators of chronic stress, exogenous adrenocorticotropin (ACTH) at 6.3 or 20.0 IU/kg/day and hydrocortisone at .25 or 2.5 mg/kg/day were administered parenterally to laying hens. Both ACTH treatments induced significant (P<.05) heterophilia, monocytosis, eosinophilia, and basophilia. Significantly elevated leucocyte counts and lymphopenia (P<.05) were observed with the high dosage of ACTH. Both hydrocortisone-treated groups developed an absolute lymphopenia and heterophilia (P<.05). The low dosage of hydrocortisone induced a significant (P<.05) monocytosis; the high dosage caused significant (P<.05) decreases in the total eosinophil and basophil counts as well as an increase in the ratio of heterophils to lymphocytes. The hemopoietic parameters, especially heterophil counts, were sensitive indicators of a hormonal stress response induced by the administration of ACTH and hydrocortisone.

Die Nephrokalzinose im Kindesalter

Ultrasonography is the method of choice for the detection of medullary or cortical nephrocalcinosis in infancy and childhood. Compared with abdominal radiographs and computed tomography even smallest calcifications are detected more accurately. Using furosemide, ACTH, steroids or high doses of vitamin D, early forms of medullary nephrocalcinosis associated with a faint hyperechogenic rim at the margins of the renal pyramids can be diagnosed by ultrasound. Idiopathic hypercalciuria, Bartter's syndrome and renal tubular acidosis cause medullary nephrocalcinosis, whereas cortical nephrocalcinosis is the result of renal vein thrombosis; primary hyperoxaluria is associated with cortico-medullary calcifications. Due to the localisation of the nephrocalcinosis and the age distribution of the diseases, sonography merely enables us to narrow down differential diagnosis.

Behavior, episodic secretion of cortisol, and adrenocortical reactivity in bulls subjected to tethering

To study the effect of individual housing on behavior and adrenocortical activity, eight bulls were moved to a novel housing environment and subjected to 5 weeks of tethering in individual stanchions with a concrete and partially slatted floor. During the first and fourth week, resting behavior and episodic cortisol secretion were analyzed over two 24-hr periods and compared to those of eight control bulls kept free on deep straw. In addition, in the fifth week adrenocortical reactivity after ACTH(1–24) stimulation was analyzed in all subjects. Resting behavior was markedly influenced by type of housing. Although duration of lying down over 24 hr was similar in tethered and control bulls, the number of periods of lying down was significantly reduced and the frequency of investigating the lying area prior to lying down was significantly increased in tethered bulls. In the first week of study, the cortisol secretory patterns of experimental and control bulls differed. The frequency of secretory episodes was significantly reduced, and the mean amplitude of the episodes increased, though not significantly in experimental compared with control bulls. After 4 weeks of tethering, however, the secretory pattern had returned to levels similar to those of control bulls. Despite this return of the basic cortisol secretion, adrenocortical reactivity after a high dosage of ACTH(1–24) was significantly reduced in tethered bulls. The results suggest that an adaptation to tethering at the brain-pituitary level does not occur, but that the return of the basal cortisol secretion could be due to changes at the adrenocortical level.

Studies on the mechanisms of ACTH-induced inhibition of aldosterone biosynthesis in the rat adrenal cortex

In rats, chronic treatment with high doses of ACTH (10-40 micrograms/100 g body weight per day) leads to a marked reduction in aldosterone synthesis by adrenal capsules. The possibility that this inhibition is secondary to a decrease in plasma potassium levels or in renin angiotensin system (RAS) activity has been explored. The effects of chronic ACTH treatment were compared in (I) animals in which the endogenous RAS activity was stimulated by restricting dietary sodium intake, (II) animals in which plasma angiotensin II was increased by infusion from implanted osmotic minipumps and (III) animals which received supplementary potassium and in which hypokalaemia was prevented. In all cases, rates of aldosterone biosynthesis in vitro by adrenal capsules were decreased in ACTH-treated animals to an extent similar to those in untreated controls. In addition, ACTH treatment of hypophysectomized rats resulted in a similar inhibition of aldosterone biosynthesis to that found in sham-operated controls. It may be concluded that the ACTH-induced reduction of aldosterone biosynthesis is independent of the secretion of other pituitary hormones, and cannot be simply ascribed to either a reduction in RAS activity or in plasma potassium levels. The results are consistent with the view that the effects of chronic ACTH treatment are mediated by a direct action on the zona glomerulosa cell, which leads to its transformation into a zona fasciculata-like form.

Developmental changes in the corticosterone response to corticotrophin and in the adrenal corticosterone content of rapid and slow growing strains of chickens(Gallus domesticus)

1. The high sensitivity of the immature domestic fowl to corticotrophin (ACTH) has been confirmed. The minimal effective dose was age-dependent, and decreased from 2 IU/kg BW in 1-d-old chicks to 0.4 IU/kg BW in 12-d-old chicks. 2. Increasing doses of ACTH evoked similar maximal corticosterone responses but the time to return to basal values increased with increasing dose of ACTH in both a broiler and layer strain. 3. Maximal corticosterone responses to ACTH occurred earlier in hatched chicks compared with embryos, and were delayed in embryos and young chicks of the layer strain compared to those of the broiler strain. 4. Strain differences in basal concentrations of corticosterone as well as in the response to ACTH occurred at a time when there were differences in the corticosterone content of the adrenals.

Treatment of infantile spasms with high‐dose ACTH

Fifteen children with infantile spasms and a hypsarrhythmic EEG defined by EEG-videotelemetry monitoring received a regimen of high-dose (150 IU/m2/d) ACTH for their seizures. We carried out an endocrinologic evaluation before and after initiation of the ACTH and conducted a time course study of plasma ACTH and cortisol levels after ACTH dosing. Spasms were controlled and the EEG normalized in 14 of the 15 children. Prior to starting ACTH therapy all the patients had normal prolactin, insulin, cortisol, and ACTH levels in plasma and normal thyroid function. Although the pattern of rise of ACTH levels in plasma after ACTH dosing was similar in all the children, there was great individual variation in the absolute concentrations. However, both the pattern of rise and absolute level of cortisol in plasma after ACTH was highly predictable in all patients. Plasma cortisol rose rapidly within 1 hour of ACTH administration and continued a slower rise for 12 to 24 hours after the ACTH dose. High-dose ACTH therapy seems quite effective in infantile spasms, perhaps because of a sustained high level of plasma cortisol. This sustained plateau of cortisol may be more effective in controlling infantile spasms than the pulse effect expected with oral steroids or lower doses of ACTH.

Evidence for Cholinergic Modulation of Aldosterone Secretion in Man

Acetylcholine stimulates aldosterone secretion in bovine glomerulosa cells in vitro via specific cholinergic receptors. In this study we examined the effect of peripheral muscarinic blockade with atropine on metoclopramide-, angiotensin-II-, and ACTH-stimulated aldosterone secretion in man. Atropine (0.6 mg, iv) administered 10 min before MCP delayed the onset of the plasma aldosterone response and attenuated the mean peak response from 502 +/- 103 (+/- SE) to 322 +/- 72 pmol/L (P less than 0.05) without affecting zero time mean plasma aldosterone levels (144 +/- 28 vs. 136 +/- 36 pmol/L for control and atropine, respectively). This inhibitory effect was not mediated by changes in PRA or plasma potassium or ACTH (as reflected by cortisol) concentrations. Atropine also attenuated the plasma aldosterone response to a low dose angiotensin II infusion (2 ng/kg.min; control, 449 +/- 99 pmol/L; atropine, 297 +/- 78 pmol/L; P less than 0.05). In contrast, atropine had no effect on the plasma aldosterone response to a bolus dose (250 micrograms) of ACTH. Neither atropine (0.6 mg, iv) nor the cholinergic muscarinic agonist bethanechol (5 mg, sc) alone elicited a change in plasma aldosterone. Collectively, these data provide evidence for cholinergic modulation of aldosterone secretion in man. We conclude that cholinergic mechanisms may facilitate the aldosterone responses to angiotensin-II and metoclopramide, but not to ACTH.

Effects of the adrenal steroidogenesis inhibitor trilostane on serum cortisol concentrations and growth in pigs

ABSTRACTThere is evidence that the growth of female rats and sheep may be constrained by physiological concentrations of glucocorticoid hormones. This study was designed to examine the effects of trilostane, an inhibitor of adrenal steroidogenesis, on serum cortisol concentrations and growth in pigs.First, trilostane was tested at three doses (250 mg, 500 mg and 1000 mg per pig) to examine its effect on serum cortisol concentrations. A reduction in serum cortisol concentration was observed 2 to 4 h after oral administration of trilostane (P &lt; 0·05) and the adrenal response to a challenge dose of ACTH was reduced 4 to 6 h after administration (P &lt; 0·05), at all doses tested. In a second experiment, trilostane (9·24 mg/kg body weight) was administered orally to 10 pigs twice daily for 35 days to examine its effects on growth rate. A further 10 pigs received a placebo. Trilostane did not affect weight gain or carcass composition, but caused a reduction in food intake (P &lt; 0·05). Adrenal weight was increased by trilostane treatment and liver weight was reduced.These results show that trilostane is effective at lowering serum cortisol concentrations acutely, but suggest that physiological concentrations of glucocorticoid hormones may not retard growth rate in barrows.

Adrenal responses to calcitonin gene‐related peptide in conscious hypophysectomized calves.

1. Right adrenal and various cardiovascular responses to an intra-aortic infusion of calcitonin gene-related peptide (CGRP; 4 micrograms min-1) have been investigated in the presence and absence of exogenous adrenocorticotrophin ACTH1-24 (2 or 5 ng min-1 kg-1, I.V.). The adrenal clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-7 days previously. 2. At the higher dose (5 ng min-1 kg-1) the I.V. infusion of ACTH raised mean plasma ACTH concentration by about 1000 pg ml-1 and mean right adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal function, other than to produce moderate adrenal vasodilatation. In contrast, in the absence of exogenous ACTH, the same dose of CGRP produced a substantial rise in cortisol output, which rose steadily to a peak mean value of 409 +/- 31 pg min-1 kg-1 at 10 min. It also significantly inhibited the release of free, but not of total, met5-enkephalin-like immunoreactivity from the gland (P less than 0.001) together with a significantly greater fall in adrenal vascular resistance (P less than 0.001). 3. At the lower dose of ACTH (2 ng min-1 kg-1, I.V.) CGRP raised mean plasma cortisol output from 314 +/- 31 to 486 +/- 44 ng min-1 kg-1 (P less than 0.01) and this effect was not attributable to an increase in the adrenal presentation rate of ACTH. 4. It is concluded that this peptide exerts a steroidogenic action on the adrenal cortex which is manifest in the absence of exogenous ACTH in the functionally hypophysectomized calf.

Chronic ACTH treatment increases striatal dopamine D-2 receptor binding in developing rat brain

ACTH has been reported to decrease elevated levels of dopamine metabolites in the CSF of patients with infantile spasms who respond clinically to ACTH therapy. To study the possible role of dopamine receptors in the effect of ACTH, we treated rat pups for thirty days with 40 IU/kg subcutaneously of porcine ACTH or with normal saline. Using 10 nM 3H-spiperone and sulpiride to determine nonspecific binding, specific binding of D-2 receptors increased significantly (46%) in the striata of ACTH-treated rats when compared to controls. No significant difference in specific binding was found in the nucleus accumbens. Protein concentration was significantly decreased by ACTH treatment. Saturation studies will be necessary to determine if the increase in dopamine receptor binding induced by a high dose of ACTH represents a change in receptor density or affinity. The effect of lower clinical doses of ACTH on dopamine receptors warrants study.