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Biomedical subjects

W E Nicholson

Publications and source records attributed to W E Nicholson.

At least 19 recordsLinked to original sources
PubMed1992

Lymphocyte-derived adrenocorticotropin is insufficient to stimulate adrenal steroidogenesis in hypophysectomized rats.

Cells of the immune system can produce and respond to peptide hormones associated with the endocrine system. However, the physiological significance of these endocrine-immune interactions is not known. It has been postulated that cells of the immune system, when stimulated with viruses that induce interferon-alpha, produce sufficient levels of ACTH to stimulate adrenal steroidogenesis and, thus, function as an auxiliary source of ACTH that may have a role in the response to stress. However, we have confirmed that levels of ACTH-related peptides produced by immunocompetent cells are far lower than those produced by the pituitary, raising questions about the ability of lymphocyte-derived ACTH to stimulate adrenal function. Furthermore, we have rigorously examined this issue using intact and hypophysectomized rats treated with Newcastle disease virus. Although high levels of interferon-alpha were produced by both intact and hypophysectomized rats, and the plasma corticosterone concentration increased dramatically in intact animals, corticosterone remained undetectable in hypophysectomized rats. The lack of a corticosterone response in these animals was not due to adrenal insensitivity to ACTH, as shown by a normal rise in corticosterone following Cosyntropin injection 8 h after hypophysectomy. The findings demonstrate that levels of ACTH produced by nonpituitary sources in response to viral infection are not sufficient to stimulate adrenal steroidogenesis.

Adrenal Cortex Hormones↗
PubMed1991

Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test.

Adrenal response to iv administration of 1-24 ACTH (250 micrograms) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 +/- 50 vs. 590 +/- 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 +/- 50 vs. 144 +/- 36 nmol/L, p less than 0.01) and at 15 min (541 +/- 61 vs. 433 +/- 52 nmol/L, p less than 0.02). This difference in response was no longer notable at 30 min (629 +/- 52 and 591 +/- 52 nmol/L). We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 micrograms 1-24 ACTH. Using 1 micrograms ACTH, the 30-min response did not differ from that to 250 micrograms (704 +/- 72 vs. 718 +/- 55 nmol/L, respectively). However, the 60-min response to 1 microgram was significantly lower (549 +/- 61 vs. 842 +/- 110 nmol/L, p less than 0.01). Using this low dose ACTH test (1 microgram, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 micrograms test, but had a reduced response to 1 microgram. The stability of 1-24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 micrograms/ml in glass tube and 0.5 micrograms/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions. We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Role of protein kinase-C in the adrenocorticotropin secretory response to arginine vasopressin (AVP) and the synergistic response to AVP and corticotropin-releasing factor by perifused rat anterior pituitary cells.

Arginine vasopressin (AVP) stimulates biphasic release of ACTH from anterior pituitary corticotrophs. The response consists of an initial transient spike phase lasting less than 3 min and a subsequent sustained plateau phase that persists for as long as AVP is present. AVP also acts synergistically with CRF on ACTH release. We have previously shown that the initial spike phase of the response mainly requires release of intracellular Ca2+ and is independent of calmodulin, whereas the sustained plateau phase, like the monophasic sustained response elicited by CRF, involves the influx of extracellular Ca2+ via L-type voltage-sensitive Ca2+ channels and activation of calmodulin. We have also shown that the synergism between AVP and CRF does not require extracellular Ca2+ influx. In this study we examined the role of Ca2+/phospholipid-dependent protein kinase-C (PKC) in the two phases of the response to AVP and in the synergism between AVP and CRF. We exploited the observation that prolonged exposure to phorbol esters down-regulates PKC. Dispersed adult male rat anterior pituitary cells were incubated in static suspension culture for 4-5 days, 0.5 microM phorbol 12-myristate 13-acetate (PMA) or 0.0005% dimethylsulfoxide vehicle alone was added, and the incubation was continued for 24 h. The cells were preperifused with PMA-free perifusion medium for 3 h and then perifused with various agents for 10-20 min. Effluent fractions were collected every 30 sec or 1 min and subjected to ACTH RIA. Pretreatment with PMA inhibited the subsequent response to 100 nM PMA and 100 microM dioctanoylglycerol, but not to 5 microM forskolin or to depolarization with 56 mM KCl, demonstrating specific down-regulation of PKC. PMA pretreatment had no effect on the initial spike phase of the response to AVP, but inhibited the sustained plateau phase by 57% (P less than 0.005) and, consequently, the integrated total response by 33% (P less than 0.05). Pretreatment had no effect on the response to CRF. However, pretreatment with PMA completely blocked both phases of the synergistic response to the combination of AVP and CRF. These results indicate that activation of PKC is required for the sustained phase of the response to AVP and both phases of its synergistic interaction with the protein kinase-A pathway, but is not involved in the initial spike phase of the response to AVP, which presumably is mediated by inositol 1,4,5-trisphosphate-stimulated mobilization of intracellular Ca2+, or in the independent activation of the protein kinase-A pathway by CRF.

Adrenocorticotropic Hormone↗
PubMed1988

Immunoreactive proopiomelanocortin (POMC) peptides and POMC-like messenger ribonucleic acid are present in many rat nonpituitary tissues.

Immunoreactive (IR) POMC peptides have been found in several rat nonpituitary tissues. We found IR-ACTH, IR-beta-endorphin (beta END), and IR-gamma MSH in extracts from the following eight rat nonpituitary tissues, listed in order of decreasing POMC peptide concentrations: testis, duodenum, kidney, colon, liver, lung, stomach, and spleen, but not in adrenal or muscle extracts. Concentrations were very low and ranged from less than 0.00003% to 0.0005% of pituitary levels. In testis, duodenum, and colon, IR-gamma MSH and IR-beta END concentrations were only 5-37% of IR-ACTH levels. Gel filtration chromatography showed that IR-ACTH and IR-beta END coeluted in a major peak of 15,000 daltons, which is slightly larger than expected for a C-terminal peptide containing rat ACTH and beta-lipotropin. There were also a minor higher mol wt peak of IR-ACTH and IR-beta END and a minor IR-beta END peak that eluted in the position of mature beta END. There was no peak of IR-ACTH that corresponded to the size of mature ACTH. To determine whether these nonpituitary tissues also contained a POMC-like mRNA, which would confirm that the peptides were synthesized locally within the tissues, we examined poly(A) RNA prepared from 10 nonpituitary tissues and total RNA from pituitary by Northern blot hybridization for the presence of a POMC-like mRNA with an exon 3 riboprobe. Pituitary contained a single POMC mRNA species of about 1000 nucleotides. A short POMC-like mRNA of about 800 bases was found in all nonpituitary tissues, except spleen and muscle. Compared to POMC mRNA levels in pituitary, the concentration of POMC-like mRNA was 0.5% in testis and 0.03-0.07% in the other tissues. The ratio of POMC-like mRNA to IR-POMC peptide concentrations in nonpituitary tissues was at least 1000 times greater than that in the pituitary. We conclude that the POMC gene is expressed in many nonpituitary tissues and that either the short POMC-like mRNA is translated much less efficiently or POMC peptides are released or degraded much more rapidly in nonpituitary tissues than in the pituitary.

Adrenocorticotropic Hormone↗
PubMed1988

Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome.

Immunoreactive (IR) POMC peptides have been detected in several human nonpituitary tissues and most pheochromocytomas and lung cancers, including those not associated with ectopic ACTH syndrome. We found IR-ACTH, IR-gamma MSH, IR-beta-endorphin (beta END), and IR-lipotropin in extracts from the following 10 normal human tissues, listed in order of decreasing POMC peptide concentrations: adrenal, testis, spleen, kidney, ovary, lung, thyroid, liver, colon, and duodenum. IR-ACTH, IR-gamma MSH, and IR-beta END were detected in all six pheochromocytomas and all 12 lung tumors (six squamous cell carcinomas, five adenocarcinomas, and one small cell carcinoma) we examined, as well as in a squamous cell carcinoma of the larynx. None of the patients had clinical evidence of ectopic ACTH syndrome. To determine whether these nonpituitary tissues and tumors actually synthesize POMC, rather than simply absorb POMC peptides from plasma, we examined poly(A) RNA prepared from these tissues and total RNA from pituitary by Northern blot hybridization for the presence of POMC-like mRNA with an exon 3 riboprobe. Pituitary contained a single POMC mRNA species of about 1150 bases. A short POMC-like mRNA of about 900 bases was found in all normal nonpituitary tissues, three of five pheochromocytomas, eight of nine lung cancers, and the laryngeal squamous cell tumor. In addition, larger POMC-like mRNA species between 1200 to 1500 bases were detected in adrenal, testis, ovary, placenta, two pheochromocytomas, and three squamous cell lung tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1988

Increased pro-opiomelanocortin-derived peptide release in myotonic dystrophy.

The response of plasma immunoreactive (IR)-ACTH, IR-beta-endorphin (beta-END) and IR-cortisol to insulin-induced hypoglycaemia, an acute stimulus to the pituitary corticotrophs through the central nervous system, and to synthetic ovine corticotrophin-releasing hormone (CRH), a direct corticotroph stimulator, were studied in normal males and males with myotonic dystrophy. Myotonics had an increased IR-ACTH and IR-beta-END response to hypoglycaemia and an increased IR-ACTH response to CRH compared with normals. Plasma IR-cortisol response were not different in either group of subjects to both stimuli. This neuroendocrine abnormality in myotonic dystrophy may represent a manifestation of the purported specific cell membrane defect underlying the disease. This is the first report of an abnormality in proopiomelanocortin peptide release in myotonic dystrophy.

Adolescent↗
PubMed1987

Pituitary and hypothalamic hormones in normal and neoplastic adrenal medullae: biologically active corticotropin-releasing hormone and corticotropin.

Six normal and 8 neoplastic adrenal medullae were assayed for several immunoreactive (IR) proopiomelanocortin (POMC) and hypothalamic peptides. IR-POMC peptides were found in normal and tumor tissue in concentrations ranging from 0.0003 to 0.1% of those in pituitary. Their molecular sizes resembled those of pituitary intermediate lobe POMC peptides. No intact POMC was found. One pheochromocytoma contained fully bioactive IR-adrenocorticotropic hormone (IR-ACTH; Mr approximately 4,500) and an intermediate-sized (Mr approximately 10,000) IR-ACTH with approximately 69% bioactivity. Normal and tumorous medullae contained IR-corticotropin-releasing hormone (CRH) in concentrations ranging from 0.6 to 4% of those in hypothalamus except for one pheochromocytoma that contained 40 times that amount of IR-CRH, which was chromatographically indistinguishable from hypothalamic CRH and fully bioactive. IR-somatostatin and IR-growth hormone-releasing hormone were found in both tissue types, but IR-gonadotropin-releasing hormone and IR-thyrotropin-releasing hormone (TRH) were not, although IR-histidyl-proline diketopiperazine, a putative TRH metabolite, was found. IR-arginine vasopressin was found in two normal medullae, but not in pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1987

Corticotropin-releasing hormone: stimulation of ACTH secretion in normal man.

Synthetic ovine corticotropin-releasing hormone (oCRH) is a potent and specific ACTH secretagogue in man. Threshold and maximal i.v. doses are 0.01-0.03 and 3-10 micrograms/kg or less, but increase in frequency, severity, and duration at higher doses. oCRH produces a biphasic plasma immunoreactive (IR)-ACTH response and has a prolonged duration of action that is probably due to its long circulating half-life. Other pro-opiomelanocortin IR-peptide are secreted concomitantly in equimolar amounts. Plasma IR-cortisol concentration tends to follow that of ACTH, but also reflects cortisol's longer circulating half-life and the fact that acutely the maximally-stimulating plasma IR-ACTH level is about 45 pg/ml. oCRH is as effective given s.c. as i.v., but intranasal administration is only 1% as effective. Sex and age have no effect on the plasma IR-ACTH and IR-cortisol responses to oCRH. The time of day of oCRH administration has little influence on the plasma IR-ACTH response, but the plasma IR-cortisol response is much greater to oCRH given later in the day than early in the morning. Plasma IR-ACTH response to oCRH is more dependent on the basal plasma IR-cortisol level than the time of day. Arginine vasopressin given at the same time as oCRH potentiates 4-fold the plasma IR-ACTH response to oCRH alone, almost to levels obtained with insulin-induced hypoglycemia. However, oCRH administered at the onset of insulin-induced hypoglycemia does not cause higher plasma IR-ACTH levels, indicating that endogenous CRH levels are maximally-stimulating during the hypoglycemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1986

Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture.

Bordetella pertussis synthesizes a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changed the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. We conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is this response that explains the subsequent acceleration of hormone release.

Adenylate Cyclase Toxin↗
PubMed1985

Effect of subcutaneous and intranasal administration of ovine corticotropin-releasing hormone in man: comparison with intravenous administration.

Long term use of ovine corticotropin-releasing hormone (oCRH) requires a convenient route of administration. The effects of 0.3, 3, and 30 micrograms/kg BW synthetic oCRH given as a sc injection and of 10 and 30 micrograms/kg given as an intranasal spray were studied in 10 normal men in the late afternoon. Basal plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol levels were 14 +/- 1.9 pg/ml and 4.3 +/- 0.4 microgram/dl (mean +/- SEM). Peak IR-ACTH levels (mean +/- SEM) were 43 +/- 5.5, 53 +/- 8.1, and 64 +/- 8.9 pg/ml after the 0.3, 3, and 30 micrograms/kg doses of oCRH given sc, respectively, and 23 +/- 4.3 and 36 +/- 4.8 pg/ml after the 10 and 30 micrograms/kg doses of oCRH given intranasally, respectively. The lowest sc dose and both intranasal doses caused only single IR-ACTH peaks. After 3 and 30 micrograms/kg sc oCRH, IR-ACTH rose by 15 min, reached an initial peak at 45-60 min, fell rapidly until 90-120 min, and rose to a second peak at 3-5 h. This biphasic response is similar to that previously found after iv administration. IR-ACTH levels remained elevated for 4, 10, and at least 16 h after 0.3, 3, and 30 micrograms/kg sc oCRH, respectively, and for 1.5 and 3 h after 10 and 30 micrograms/kg intranasal oCRH respectively. The effect on IR-cortisol was similar, but more prolonged. Compared to the iv route, sc oCRH produced similar mean peak IR-ACTH and IR-cortisol levels and had a slightly longer duration of action. Intranasal oCRH was only about 1% as effective. Peak plasma IR-oCRH levels in 2 subjects receiving 3 micrograms/kg sc oCRH were 13 and 17 ng/ml at 90 min. These peaks were lower than those after iv administration of the same dose, but the levels remained elevated longer, probably accounting for the longer duration of action of sc oCRH. Peak plasma IR-oCRH levels in 4 subjects given 10 microgram/kg intranasal oCRH were only 64-122 pg/ml, presumably reflecting poor absorption through the nasal mucosa. These results demonstrate that sc injection of oCRH is at least as effective as the iv route with respect to plasma IR-ACTH and IR-cortisol responses. The convenience of this route of administration and the prolonged duration of action of oCRH suggest the feasibility of long term oCRH use.

Administration, Intranasal↗
PubMed1985

Clinical studies with synthetic ovine corticotropin-releasing factor.

Ovine corticotropin-releasing factor (oCRF) stimulates increased plasma immunoreactive adrenocorticotropin (IR-ACTH) and IR-cortisol at threshold, half-maximal, and maximal doses of 0.01-0.03, 0.3-1, and 3-10 micrograms/kg, respectively. Side effects occur with increasing frequency, severity, and duration at doses above 1 microgram/kg. oCRF has a prolonged duration of action, at least in part because of the long circulating half-life of intact oCRF in plasma. Increasing doses of oCRF given in late afternoon progressively diminish the next morning's circadian rise in plasma IR-ACTH in normal subjects, but not in Addisonian patients or subjects receiving metyrapone, indicating that prolonged oCRF-induced hypercortisolemia is the cause. Plasma IR-lipotropins and IR-beta-endorphin rise and fall concomitantly with IR-ACTH after oCRF injection. Arginine vasopressin increases the IR-ACTH response to oCRF fourfold when given simultaneously with oCRF. Cushing's disease patients respond variably, suggesting that oCRF may not be a very useful diagnostic agent in Cushing's syndrome. However, the combination of oCRF with growth hormone-releasing factor, gonadotropin-releasing hormone, and thyrotropin-releasing hormone appears to provide a rapid and useful test of combined anterior pituitary function.

Adrenocorticotropic Hormone↗
PubMed1979

Cell-free synthesis of mouse corticotropin. Evidence for two high molecular weight gene products.

Polysomes or mRNA prepared from cultured AtT-20/D16v mouse pituitary adenocarcinoma cells direct the efficient incorporation of amino acid into newly synthesized material in the presence of wheat germ translational factors. A significant franction of the total cell-free product is specifically immunoprecipitable with corticotropin antibody purified by immune affinity chromatography. Analysis of the cell-free synthesized immunoreactive products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that two high molecular weight corticotropin species (Mr congruent to 32,500 and 28,000) are synthesized in an approximate 2:1 ratio. Neither product contains carbohydrate based upon concanavalin A chromatography or exposure to polysaccharidases. The smaller molecular weight product does not appear to arise from proteolytic processing since both species are synthesized in approximately the same ratio in cell-free reaction mixtures directed by either polysomes or mRNA. These results suggest that AtT-20/D16v cells contain two distinct mRNA poluations specifying the synthesis of two different high molecular weight forms of mouse corticotropin.

Adenocarcinoma↗
PubMed1979

Adrenoleukodystrophy and adrenomyeloneuropathy associated with partial adrenal insufficiency in three generations of a kindred.

Four cases of adrenoleukodystrophy (ALD) and one case of adrenomyeloneuropathy (AMN) have developed in a kindred over three generations demonstrating that AMN is a clinical variant of ALD. Pituitary-adrenal function studies were performed in 10 family members, including two affected males and four females identified as carriers of ALD/AMN. No pituitary-adrenal abnormality was found in the carriers. However, basal morning plasma adrenocorticotropic hormone (ACTH) levels were markedly elevated in the two males with ALD and AMN, despite the fact that they had no clinical signs of adrenal insufficiency and that morning plasma cortisol levels and their response to maximal exogenous ACTH stimulation appeared to be normal. In addition, the integrated 24-hour response to the administration were also subnormal in these two cases. Thus, people with ALD and AMN may have subclinical partial adrenocrotical insufficiency. No other endocrinologic dysfunction was identified.

Adolescent↗
PubMed1979

Human placental immunoreactive corticotropin, lipotropin, and beta-endorphin: evidence for a common precursor.

The concentrations and molecular sizes of immunoreactive corticotropin (ACTH), lipotropin (LPH, beta LPH plus gamma LPH), gamma LPH, and beta-endorphin (beta END) were determined in human placental extracts. Serial dilutions of a water extract of placenta generated competitive binding curves parallel with that of the standard in each assay. The concentrations of ACTH, LPH, gamma LPH, and beta END were 3.3, 0.8, 0.7, and 1.1 ng/g wet weight of tissue, respectively. A partially purified extract applied to a Sephadex G-50 column contained high Mr components with ACTH, LPH, gamma LPH, and beta END immunoreactivities. The extract was applied to an immune affinity chromatography column consisting of affinity-purified (1-24)ACTH antiserum covalently bound to agarose. The material that adsorbed to the column and eluted with buffer containing sodium dodecyl sulfate had ACTH, LPH, and beta END immunoreactivities, indicating that there was a component or components containing antigenic determinants for all of these peptides. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the affinity-purified placental extract revealed at least two high Mr components (Mr approximately 48,000 and 36,000) with all three immunoreactivities. These data suggest, but do not prove, that the placenta synthesizes ACTH, the LPHs, and beta END from a common precursor molecule.

Adrenocorticotropic Hormone↗
PubMed1979

Free-running circadian plasma cortisol rhythm in a blind human subject.

The plasma cortisol rhythm in man has been presumed to be an endogenous circadian rhythm, synchronized by some external stimulus to an exact 24-h period. Sleep/wake and 'social activity' cycles have been considered as candidates for this synchronizer. Previous studies have suggested that the dark/light phase shifts associated with the sleep-wake cycle may be the external synchronizer, rather than the sleep/wake cycle itself. A totally blind, but otherwise normal subject was studied for a period of 50 days. Her hourly sleep/wake status and hourly integrated mean plasma cortisol concentrations were determined, and the data were subjected to non-parametric mathematical analysis. The subject was found to have a free-running rhythm in plasma cortisol with a period of approximately 24.5 h. Her sleep/wake rhythm, determined by similar analysis, had a period of exactly 24 h. In addition to the dominant 24.5-h cortisol rhythm, there appeared to be a minor 24-h cortisol rhythm with a peak that coincided approximately with the time of awakening. It was not possible to determine whether this sleep/wake-related peak represented a minor component of the circadian rhythm, synchronized by some stimulus associated with sleep/wake activity, or merely an acute response to awakening itself. Nevertheless, the two rhythms exhibited 'beating' behaviour, resulting in maximal peak cortisol concentrations when they were in synchrony and minimal peak concentrations when they were not. It is concluded that environment dark/light phase shifts are the dominant synchronizer of the circadian rhythm in plasma cortisol concentrations in man, as they are for a variety of circadian rhythms in other living things.

Blindness↗
PubMed1979

Dopamine inhibits angiotensin-stimulated aldosterone biosynthesis in bovine adrenal cells.

The possibility that dopamine may play a role in the in vivo control of aldosterone production in man was suggested to us by reports from others; (a) that bromocriptine, a dopaminergic agonist, inhibits the aldosterone response to diuresis and to the infusion of angiotensin or ACTH; and (b) that metaclopramide, a dopamine blocking agent, causes elevations in plasma aldosterone levels. To determine whether such effects were direct or indirect, we examined the action of dopamine on aldosterone biosynthesis in isolated, bovine adrenal cells. Dopamine significantly inhibits the aldosterone response to angiotensin (P < 0.001), but does not influence basal aldosterone biosynthesis. It has previously been reported that angiotensin stimulates both the early and late phases of aldosterone biosynthesis. The present experiments demonstrated that the enhancing effect of angiotensin on the conversion of deoxycorticosterone to aldosterone (late phase of aldosterone biosynthesis) was almost completely inhibited by dopamine (P < 0.001). A significant inhibitory effect of dopamine (10 nM) was seen even when aldosterone biosynthesis was stimulated by a grossly supraphysiological concentration of angiotensin II (10 muM). However, these studies did not demonstrate any direct effect of dopamine on the early phase of aldosterone biosynthesis (cholesterol to pregnenolone) basally or when stimulated, or on the late phase of aldosterone biosynthesis under basal conditions. These in vitro studies suggest a direct inhibitory role for dopamine on the late phase of aldosterone biosynthesis, which may account for the in vivo inhibition of the aldosterone response to angiotensin in subjects treated with a dopaminergic agent.

Adrenal Glands↗
PubMed1979

A case of pituitary adrenocorticotropin-dependent Cushing's syndrome in the horse.

In the horse, a syndrome of hirsutism, hyperglycemia, glucosuria, polydipsia, polyuria, polyphagia, and progressive debilitation has been recognized. Most often the syndrome has been associated with adenomas of the pars intermedia of the pituitary and bilateral adrenal hyperplasia or nodular hyperplasia involving primarily the zona fasciculata. Previously, the syndrome has been ascribed to compression of the hypothalamus by an expanding but functionally inactive pituitary neoplasm. In the present case, with RIA determination of plasma ACTH concentrations, the syndrome was ascribed to pituitary ACTH-dependent hyperadrenocorticism and likened to human Cushing's disease.

Adrenocorticotropic Hormone↗