The Clinical Usefulness of ACTH and Cortisone

Gw, Thorn; Ph, Forsham; Tf, Frawley; Hill,; Roche, Marcel; Staehelin, D; Dl, Wilson

doi:10.1056/nejm195005252422105

Cited by 203 publications

(9 citation statements)

References 8 publications

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“…The concept of inhibition of adrenal androgen production began with Huggins and Scott in 1945 [18] , who reported that adrenalectomy depleted testicular and adrenal androgens. However, adrenalectomy also produced adrenal insufficiency, which was lethal to patients without glucocorticoid replacement therapy [19] , [20] . Since 1945, several adrenal androgen biosynthesis inhibitors were identified, such as aminoglutethimide [21] , [22] , which impaired 11β-hydroxylase, and ketoconazole [23] , [24] , [25] , which targeted 21- and/or 11β-hydroxylase, 17α-hydroxylase and 17, 20-lyase activity, to deplete circulating adrenal steroid levels, such as DHEA-sulfate [24] .…”

Section: Cyp17a1 Activity Inhibitors and Mechanisms Of Pca Resistancmentioning

confidence: 99%

Potential impact of combined inhibition of 3α-oxidoreductases and 5α-reductases on prostate cancer

Fiandalo

Gewirth

Mohler

2019

Asian Journal of Urology

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Prostate cancer (PCa) growth and progression rely on the interaction between the androgen receptor (AR) and the testicular ligands, testosterone and dihydrotestosterone (DHT). Almost all men with advanced PCa receive androgen deprivation therapy (ADT). ADT lowers circulating testosterone levels, which impairs AR activation and leads to PCa regression. However, ADT is palliative and PCa recurs as castration-recurrent/resistant PCa (CRPC). One mechanism for PCa recurrence relies on intratumoral synthesis of DHT, which can be synthesized using the frontdoor or primary or secondary backdoor pathway. Androgen metabolism inhibitors, such as those targeting 5α-reductase, aldo-keto-reductase family member 3 (AKR1C3), or cytochrome P450 17A1 (CYP17A1) have either failed or produced only modest clinical outcomes. The goal of this review is to describe the therapeutic potential of combined inhibition of 5α-reductase and 3α-oxidoreductase enzymes that facilitate the terminal steps of the frontdoor and primary and secondary backdoor pathways for DHT synthesis. Inhibition of the terminal steps of the androgen metabolism pathways may be a way to overcome the shortcomings of existing androgen metabolism inhibitors and thereby delay PCa recurrence during ADT or enhance the response of CRPC to androgen axis manipulation.

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Section: Cyp17a1 Activity Inhibitors and Mechanisms Of Pca Resistancmentioning

confidence: 99%

Potential impact of combined inhibition of 3α-oxidoreductases and 5α-reductases on prostate cancer

Fiandalo

Gewirth

Mohler

2019

Asian Journal of Urology

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“…The most detailed accounts available of the actions of cortisone and ACTH in man are those of Hench, Sprague, and co-workers (253,254), McEwen et at. (251), the adrenal hormones may "intervene in the manifestations of hypersensitivity of the body [to] inhibit the altered reactions of cells [that] so often prove more harmful than the direct toxic effects of the sensitizing agents themselves." From the present evidence, it appears that the diseased states in which adrenal hormones may be the most useful include acute rheumatic fever, arthritis, status asthmati cus, serum sickness, exfoliative dermatitis, and related states of hypersens i tivity.…”

Section: Metabolic Effects Of Cortical Steroidsmentioning

confidence: 99%

Metabolic Functions of the Endocrine Glands

Ja¹

1951

Annu. Rev. Physiol.

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As in the past several years, it has been impossible to mention here all the papers appearing in the period of review which might have been included under the title of this chapter. Emphasis has been placed on the metabolic functions of the hormones with evidence bearing on the physiology of the endocrine glands as such included only in certain instances. With few exceptions, no discussion has been attempted of papers which have been available to the author only in abstract form. THE HYPOPHYSISActivation of the adenohypophysis.-It has become apparent that most of the anterior lobe hormones, like those of the neurohypophysis, are secreted not at constant rates, but that the functioning of the gland must be controlled in such a way that the trophic hormones are released at rates varying with the physiological state and needs of the animal. The nature of the mecha nisms which may excite secretion by the adenohypophysis is now under active investigation (1, 2). Green & Harris suggested earlier that local neuro humoral stimulation of the gland might occur via pathways from hypo thalamic areas and the hypophyseal-portal blood vessels. These authors have now confirmed by direct observation in the living rat the direction of flow of blood in these vessels as from the median eminence toward and into the pars distalis (3). Harris has'further pointed out that after stalk section, re generation of the portal vessels may occur readily (4, 5). Unless measures are taken to prevent this, as by insertion of a plate of some sort, severing the direct neura1 pathways from the hypothalamus to the pituitary would not necessarily interrupt permanently the vascular connections. In stalk-sec tioned rats, Cheng et at. (6) observed maximal reduction in the adrenal ascorbic acid after injection of histamine. Later, they reported submaximal stimulation of the adrenal by histamine in hypophysectomized rats bearing intra-ocular grafts of anterior lobe tissue (7). Fortier & Selye (8), using cold as a stimulus, reported identical changes in adrenal ascorbic acid in normal or stalk-section�d rats and in hypophysectomized animals with intra-ocular grafts. I t would appear that in the rat, at least, neither neural nor vascular connections with the hypothalamus are required for increased secretion of adrenocorticotrophic hormone (ACTH) folIowing stress.

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“…Within an extremely short time the epoch-making dis covery of Hench and Kendall of the effect of these hormones in arthritis was reported. These observations opened a new era in medicine, physiology and biochemistry, and it was recognized as such by the award of the Nobel prize to Reichstein, Kendall, and Hench in 1950. The number of investigations has increased rapidly during the last 1 The following abbreviations have been used in this review. It should be noted that, unless otherwise mentioned, reference has been made to the acetoxy derivatives of the adrenal hormones: Cortisone-tl,4-pregnene-17a,21-diol-3,l1,20-trione acetate; comp ound F -tl, 4-pregnene-llt!,17 a,21-triol-3 ,20-dione acetate ; com pound A -tl, 4_ pregnen-21-ol-3,l1,20-trione acetate; compound S-tl,4-pregnene-17a,21-diol-3,20dione acetate; DOC-desoxycorticosterone; DOCA-desoxycorticosterone acetate;…”

Section: And Konrad Dobrinermentioning

confidence: 99%

Biochemistry of Steroids

Lieberman¹,

Dobriner²

1951

Annu. Rev. Biochem.

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The unique role of the steroid hormones in nearly all phases of life has been established. With the discovery of the sex hormones in the early thirties, it seemed that the physiological action of steroids was primarily concerned with the phenomena of sex. With ' the discovery of the steroid hormones of the adrenal gland in the late thirties it was soon found that these compounds had a profound influence on metabolism and that this was also true of the so-called sex hormones. Progress in a steadily expanding area of investiga tion in biology, biochemistry, and medicine was handicapped by the lack of sufficient quantities of the adrenal hormones. These hormones were for all practical purposes not available because the chemical introduction of the biologically essentially C-ll oxygen function into the steroid nucleus had not been accomplished. As a result of the brilliant work of Reichstein, Kendall, Gallagher, and Wintersteiner in the middle forties, this objective was achieved and together with the further contributions· of these investiga tors, as well as the very significant achievements of Sarett, Miescher, Wallis, and Julian, the large scale preparation of the most important cortical hor mones became practicable. Fin ally, large amounts were made available for extensive investigations. At about the same time the adrenfll-stimulating hormone of the pituitary (ACTH) became available in sufficient amounts and in a usable stage of purity so that both hormones were at hand for the study of the essential physiological processes controlled by the internal secre tions of the adrenal. Within an extremely short time the epoch-making dis covery of Hench and Kendall of the effect of these hormones in arthritis was reported. These observations opened a new era in medicine, physiology and biochemistry, and it was recognized as such by the award of the Nobel prize to Reichstein, Kendall, and Hench in 1950. The number of investigations has increased rapidly during the last 1 The following abbreviations have been used in this review. It should be noted that, unless otherwise mentioned, reference has been made to the acetoxy derivatives of the adrenal hormones

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The Clinical Usefulness of ACTH and Cortisone

Cited by 203 publications

References 8 publications

Potential impact of combined inhibition of 3α-oxidoreductases and 5α-reductases on prostate cancer

Potential impact of combined inhibition of 3α-oxidoreductases and 5α-reductases on prostate cancer

Metabolic Functions of the Endocrine Glands

Biochemistry of Steroids

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