Michael Finkelstein

Estimation of Steroid Estrogens by Fluorimetry.

Summary 1. A method for estimation of estrone, estradiol, and estriol in pure solution is based on the observation that these substances afford products with a green fluorescence when heated in phosphoric acid. 2. The fluorescent response of the urinary estrogens is over a wide range a linear function of their concentration. The error of the fluorimetric assay in suitable ranges of estrogen concentrations (estradiol, 0.5-2.5 γ; estrone, 1.0-5.0 γ; and estriol, 1.0-10.0 γ) does not exceed ± 3%. 3. Sterols which do not contain a conjugated double bond, some naturally occurring nonsteroid aromatic substances, and many common constituents of biological material give no fluorescent response under the conditions of the test. 4. Estrogen fluorimetry appears to compare favorably as to sensitivity, specificity and simplicity with previously described methods of estrogen assay.

Microdetermination of steroid estrogens in urine by fluorometry.

Summary 1. A quantitative method for the determination of estradiol, estrone and estriol in urine, based on the fluorescence of these substances when treated with phosphoric acid, is described. 2. The method is more accurate, sensitive and specific than other known biological or colorimetric tests. 3. The recoveries of estradiol were above 80%; of estrone between 70 and 80%; and of estriol between 50 and 60%. The mean experimental error was ± 10%. 4. The described method permits the determination of estriol in urine in quantities not hitherto detectable.

Estimation of testosterons in human urine

Abstract A method, based on the enzymic conversion of testosterone to estradiol-17β, has been elaborated for the estimation of testosterone in human urine. The range of excretion of testosterone in healthy human males in the 20–40 year age group was 5.0–79.0 μg/24 hrs. and in normal women of the reproductive age it was

The metabolism of 3H-estradiol-17β in human breast cancer in organ culture

Abstract The metabolism of 3 H-estradiol- 17 β was studied in twelve tissue samples of human female breast grown in organ culture. Five samples were from carcinomas, three were from uninvolved tissue from the cancer-bearing breast, two were from fibroadenomas and two from cystic mastitis. In all cases, estradiol- 17 β was metabolized to estrone. The non-cancerous tissue, fibroadenomas and cystic mastitis showed greater conversion of estradiol- 17 β into estrone than the cancerous tissues. No indication was obtained for conversion of estradiol- 17 β into estriol.

Steroidogenesis in a virilizing ovarian tumour.

A metabolic study with tissue from a virilizing arrhenoblastoma, using as precursors [7‐3H]pregnenolone, [7‐3H]17α‐hydroxypregnenolone, [4‐14C]17α‐hydroxy‐progesterone and [4‐14C]testosterone, revealed that in spite of a deficient activity of 3β‐hydroxysteroid dehydrogenase‐5‐isomerase the overall production of test‐osterone was compensated by an increased activity of a lyase converting[4‐14C]17α‐hydroxyprogesterone to testosterone (via androstenedione) and was comparable to the production obtained by normal ovarian tissue. The masculinizing effects of the tumour in vivo were most probably caused by accumulation of testosterone due to deficiencies in enzymes catabolizing testosterone to 17‐ketosteroids and its aromatization to oestrogen. The unique property of the arrhenoblastoma to convert [4‐14C]17α‐hydroxyprogesterone to [4‐14C]11‐deoxycortisol (Reichsteins compound S) suggests an adrenal origin of the tumour which may explain its limited capacity to aromatize testosterone.

Isolation of 20α and 20β 5β-pregnane-3α, 17α, 20, 21-tetrol (hexahydroreichstein's compound-S) in a case of congenital adrenal hyperplasia

Abstract 5β-Pregnane-3α, 17α, 20α, 21-tetrol (l) and 5β-pregnane-3α, 17α 20β, 21-tetrol (II) have been isolated and identified from the urine of a girl with congenital adrenal hyperplasia. The total 5β-pregnane-3α, 17α, 20(α+β),21-tetrol consisted of 60% of I and 40% of II. The final identity of the compounds was established by gas chromatography — mass spectrometry. The mass spectra of the two trimethylsilyl isomers were closely related to each other in contrast to the spectra of five other pairs of C 21 -C-20(α and β)-hydroxy steroid-trimethylsilyl-ethers. The mass spectra of free I and II also exhibited many common features, but were less similar to each other than their trimethylsilyl derivatives.

Blood Concentration of P-chloro-xylenol in Man Following Parenteral, Percutaneous and Rectal Application.

Summary The presence of free p-chloroxylenol (CX) in the blood shows that this substance is resorbed after parenteral, oral, rectal, as well as percutaneous application. Only 1% of the amount of CX applied was detected in the blood. In percutaneous treatment, the skin acts as a depot from which CX is slowly resorbed into the blood, and as a result a prolonged circulation of CX in active form in the blood is obtained. The prolonged circulation of CX in the blood in active form following different routes of administration renders its chemotherapeutic efficacy in man comprehensible.

Studies on the C-11 and C-21 steroid hydroxylation sequence in subcellular fractions of human adrenals

Abstract The possibility of Cortisol biosynthesis proceeding through a C-11β→ C-21-hydroxylation sequence of 17-hydroxypregnenolone and 17-hydroxyprogesterone was investigated in vitro in the normal human adrenal and in an adrenal adenoma. The mitochondrial 11β-hydroxylase activity towards the C-21-hydroxy vs C-21-deoxy substrates and the microsomal 21-hydroxylase activity towards the C-11-deoxy vs C-11β-hydroxy substrates was compared. The mitochondria converted compound S to cortisol with a high efficiency, while the 11β-hydroxyla-tion of the C-21-deoxysteroids proceeded only to a limited extent. Moreover, when present in equimolar, ound S inhibited the 11β-hydroxylation of C-21-deoxysteroids. The microsomes converted 21-deoxycortisol to cortisol, but this 21-hydroxylation was 10-fold lower than that of 17-hydroxy-progesterone to compound S. From the combined results of the respective hydroxylations by the mitochondria and microsomes it is concluded that in the human adrenal the alternative pathway to cortisol via the C-11β→ C-21-hydroxylation sequence does not seem to be significant.

Coelomic mesothelium-like cells in the ovarian stroma of patients with the polycystic ovary syndrome (Stein-Leventhal syndrome)

Abstract Cells resembling the early coelomic epithelium have been described in the ovaries of patients with the polycystic ovary syndrome. These undifferentiated cells were located deep in the loose ovarian stroma, scattered among various connective tissue elements. The possibility has been discussed that these cells may originate from the common primordium of the adrenogenital epithelium persisting in the ovary in a protodifferentiated state.

The effects of cortisone and of estradiol given to pregnant rats on the structural differentiation of the adrenal cortex and the ovary in their offspring.

Administration of estrogens to neonatal rats has been reported by Gorski (1) to inhibit the maturation of their ovaries, leading later to sterility. Estrogens in high doses injected into pregnant rats may cross the placenta and lead to sterility in the female young. The ovaries of these female offspring, according to Adams-Smith (2,3), exhibit structural changes resembling those seen in the human micropolycystic ovary. Similarly, administration of corticosteroids to pregnant rats or to neonates adversely affects the early differentiation of the adrenal cortex (4). However, the structural damages occurring in the fetal adrenal and ovary by the transplacental effect of estrogens or corticoids have not been described.