Melvin J. Bryson

The synthesis and metabolism of progesterone in the human and bovine ovary

Abstract 1. 1. The biosynthesis of progesterone from [1-14C]acetate has been demonstrated. 2. 2. By means of in vitro incubations of [4-14C]progesterone and [4-14C]androstenedione in human ovarian tissue, a continuous spectrum of intermediate compounds leading to the synthesis of estrogens has been demonstrated. Presumption evidence has been obtained for the following products: 6β-hydroxyprogesterone, pregnanedione, allopregnanedione, 20a-hdyroxypregnene-3-one, 20β-hydoxypregnene-3-one, 17-hydroxyprogesterone, 17α-20ζ-dihydroxypregnene-3-one, 20ζ-hydroxypregnane-3-one, androstenedione, estrone, and estradiol-17β.

Amniotic fluid lecithin/sphingomyelin ratio as an assessment of fetal pulmonary maturity

Abstract The method of Gluck and associates 1 for estimating the lecithin/sphingomyelin ratio in amniotic fluid has proved to have a high degree of accuracy in predicting fetal lung maturity. One hundred and eighty-five samples of amniotic fluid from 167 patients in various weeks of gestation were assayed. A lecithin/sphingomyelin (L/S) ratio of 1.5 or less indicated an immature fetal lung, and, in all spontaneously delivered infants, where the values were in this range, the infant developed the respiratory distress syndrome (RDS) and hyaline membrane disease. An L/S ratio of 1.51 to 1.80 suggested a transitional fetal lung in which some of the infants developed RDS, and possibly a mild hyaline membrane disease, but all recovered. If the L/S ratio was over 1.80, the lung was considered to be mature for normal function in the external evironment, and respiratory distress did not develop. The L/S ratio in amniotic fluid is a rapid, accurate method to assess fetal lung maturity and is an invaluable aid in the management of increased risk pregnancies and in cases of repeat cesarean section where the gestational age is unknown.

Studies of the oxidation state of partially purified adrenal cortex mitochondrial cytochrome P-450 and difference spectra induced by deoxycorticosterone and metopirone.

Abstract Cytochrome P-450 prepared from extracts of adrenal gland cortex mitochondrial acetone powder exists in the oxidized state as it will not complex with carbon monoxide. Both deoxycorticosterone and Metopirone will induce spectra in the preparation in the absence of oxygen and reductase components. Metopirone displaces the deoxycorticosterone-induced difference spectrum of the cytochrome P-450 preparation, but excess deoxycorticosterone does not influence the Metopirone-induced spectrum suggesting different complexing mechanisms for the two compounds. The observations are consistent with the concept that the steroid-induced spectrum is the result of a direct complexing with ferric cytochrome P-450, or a closely associated companion pigment dependent upon the ferric state of cytochrome P-450. Current observations indicate experimentally separable reaction steps in the overall system of 11β-hydroxylation.

The effect of cesarean section on respiratory distress in the presence of a mature lecithin/sphingomyelin ratio

Three hundred and six amniocenteses were performed on 240 patients to determine the lecithin/sphingomyelin ratio. The indications were maternal diabetes mellitus, Rh disease, hypertension, placenta previa, repeat cesarean sections, unknown gestational age, and toxemia. Respiratory distress and hyaline membrane disease were predicated correctly in all cases. There were 104 vaginal deliveries and 136 cesarean sections in this study. There was no apparent indication that the mode of delivery had any bearing on the development of respiratory distress or hyaline membrane disease.

Is mevalonic acid a precursor of the corticosteroids

Abstract Bovine adrenal tissue preparations (whole homogenates or a combination of microsomal and supernatant fractions) readily convert acetate-1-C 14 to corticosteroids, 14 of which have been isolated and identified. In parallel experiments with aliquots of the same adrenal tissue preparations, mevalonate-2-C 14 was not found to be incorporated into any of these corticosteroids.

The role of phosphopyridinenucleotides in the metabolism of cortisol by peripheral tissue

Abstract 1. 1. Cortisol incubated with muscle tissue is metabolized to cortisone, dihydrocortisol, corticosterone, 11-β-hydroxyandrostenedione, Reichsteins substances E and U, dihydrocortisone, Kendalls Compound A and adrenosterone. 2. 2. The reaction, cortisol → cortisone is TPN specific. DPN appears to inhibit the reaction. No evidence was obtained for the presence of a transhydrogenase in muscle tissue. Reduction at C-4, 5, and C-20 appears to be TPNH specific. 3. 3. Studies of the metabolism of cortisone in muscle and liver indicate that the major product in liver is cortisol. The major product in muscle is Reichsteins substance U.

Comparative metabolism of progesterone in proliferative human endometrium and myometrium

Abstract In contrast to hepatic metabolism of progesterone, which gives rise to 5β-pregnane derivatives, both endometrium and myometrium are unique in that they reduce the Δ 4 bond of progesterone to form predominantly allo (5α) pregnane products. Differences in progesterone metabolism also exist between endometrium and myometrium. These metabolic differences may relate to the different hormonal effects of progesterone (secretory activity in the endometrium; inhibition of muscle contraction in the myometrium). The major product in endometrium is an unknown dihydroxy compound. 4-Pregnen-20α-ol-3-one is the major product of myometrium. Six additional products have been identified in endometrium; 3 in myometrium. The metabolic pathways of progesterone observed are evaluated in light of possible progesterone hormonal mechanisms.

Preparation of a soluble progesterone 17α-hydroxylating system

Abstract Examination of differentially centrifuged homogenates of bovine adrenocortical tissue reveals that the steroid 17α-hydroxylating system resides primarily in the particle-free cytoplasm. Preparations are relatively labile. Higher activity is noted in fresh unfrozen glands than from frozen ones. 17-Hydroxylation is inhibited less in higher pH media and in media containing p -chloromercuribenzoate than is 21-hydroxylation.

Conversion of pregnenolone to progesterone by human endometrium in vitro

Abstract Pregnenolone-4-14C was incubated in vitro with human endometrium. One of the products isolated by reverse isotope dilution and paper chromatographic techniques was shown to be progesterone. It is concluded from this observation that the endometrium possesses a functional 3β-ol-dehydrogenase-isomerase enzymic system.

Two adrenal gland cytochrome P-450 entities evidenced by metyrapone-induced spectra

Abstract 1. Marked diminution in the metyrapone-induced 425-nm difference spectrum occurs when 17-hydroxyprogesterone is added to microsomal preparations, but only a low magnitude response is observed when this steroid is introduced into mitochondrial fractions exhibiting metyrapone spectra. Deoxycorticosterone induces spectra in both acellular fractions, but does not influence the magnitude of metyrapone spectrum. 2. Diminution of the microsomal metyrapone absorption peak after addition of 17-hydroxyprogesterone, appears to be primarily due to summation of the 420-nm absorption minimum induced by 17-hydroxyprogesterone and the 425-nm absorption maximum induced with metyrapone. 3. Metyrapone cancels deoxycorticosterone-induced spectra occurring either in microsomes or mitochondria and attains a magnitude identical to that attained in the absence of deoxycorticosterone. 4. Addition of metyrapone to microsomal preparations containing deoxycorticosterone results in the same difference spectrum as that manifest by metyrapone alone, suggesting complete displacement of the spectral inducing elements of deoxycorticosterone in preference to those of metyrapone. Such a manifestation, however, does not occur in respect to 17-hydroxyprogesterone. The spectral shift which occurs when metyrapone is added to preparations containing 17-hydroxyprogesterone is distinct from metyrapone alone. When metyrapone is added to the reference cuvette, the sample cuvette reveals the 17-hydroxyprogesterone spectrum; when 17-hydroxyprogesterone is added to the reference cuvette the metyrapone spectrum is revealed indicating independence of the two substrates in inducing their respective difference spectra.