Study on the inactivation mechanism of androgens in rheumatoid arthritis: excretory rate of free and conjugated 17-ketosteroids.

Unconjugated, sulpho- and glucurono-conjugated androgen hormone metabolites have been determined in the urine of patients with rheumatoid arthritis. An increase in the excretory rate of unconjugated 5 beta-reduced 17-ketosteroids and a decrease in that of 17-ketosteroid conjugates, especially in dehydroepiandrosterone sulphate and in the sum of dehydroepiandrosterone, etiocholanolone and androsterone glucuronoside were observed. In contrast to unconjugated metabolites, there was less significant change in the 5 beta-metabolite conjugates in urine. Corticosteroid treatment resulted in an additional decrease of metabolite excretion by patients. Further study is necessary to determine the causative factors in the altered steroid pattern observed in this severe, non-endocrine disease.     

Structure determination of 3 beta, 17-dihydroxy-17 alpha-pregn-5-ene-20-one

The title compound was synthesized as part of an effort to determine the identity of an abnormal steroid metabolite present in the urine of a patient exhibiting pronounced gynecomastia. The X-ray investigation of the synthesized compound showed that the 20-carbonyl of the 17 alpha oriented side chain lies under the D ring, and does not participate in hydrogen bonding in the crystal lattice. This conformation appears to be stable and sufficiently shielded that it is unlikely to make a major contribution to possible protein interactions.     

D-homoannulation of 17alpha,21-dihydroxy-20-keto steroids (corticosteroids)

Synthetic corticosteroids are widely used as anti-inflammatory agents. Mechanisms of their degradation continue to be studied. D-ring homoannulation is a well-known metabolic pathway for steroids in vivo. The rearrangement with aluminium trichloride of the commercial anti-inflammatory drugs hydrocortisone, cortisone and dexamethasone is here presented. The structures of the corresponding 17a-keto-17-hydroxy-D-homosteroids are established by mono- and two-dimensional NMR analysis. Inversion of the alpha-configuration of C-16 is observed in the Lewis acid assisted D-homoannulation of dexamethasone.     

A simple radioimmunoassay for plasma cortisol and 11-deoxycortisol (17, 21-dihydroxy-4-pregnene-3, 20-dione).

A simple procedure for the measurement of cortisol and 11-deoxycortisol in plasma or serum is described. One-half ml. of plasma is extracted with methylene chloride. Separation of cortisol and deoxycortisol is achieved by a Sephadex LH-20 mini-column. The assay itself is achieved by the use of a commercially available cortisol kit employing rabbit anti-cortisol coated tubes. This antibody exhibits a 20% crossreactivity with 11-deoxycortisol. This procedure is extremely useful in the assessment of a pituitary-adrenal reserve in the Metyrapone test.