Showing papers on "Steroid biosynthesis published in 1975"

Familial glucocorticoid deficiency. Studies of diagnosis and pathogenesis.

Abstract: The clinical and biochemical findings are described in 2 brothers who had intermittent hypoglycaemia generally precipitated by the "stress" of infection. Both were tall and pigmented. Both boys showed a failure of adrenocortical response to ACTH which was progressive in the eldest boy. The diagnosis of familial glucocorticoid deficiency (hereditary adrenocortical unresponsiveness) was confirmed by the absence of electrolyte imbalance even on a low sodium diet, and by very high levels of ACTH in plasma. High levels of deoxycorticosterone (DOC) were found in both children with normal levels of other plasma corticosteroids. It is suggested that the high levels of DOC may be in some way related to the apparent persistence of a "fetal" type of adrenocortical steroid biosynthesis for 18 months or more in these boys. After the diagnosis, established by relatively simple methods, treatment with cortisone acetate has 0een highly effective.

Steroids and steroid metabolism in plant tissue cultures.

Abstract: The steroids which have been isolated from plant callus and suspension cultures are reviewed. In addition, the research involving the use of plant tissue cultures to investigate steroid biosynthesis and metabolism is summarized.

Alternative pathways of steroid biosynthesis in gonads and hepatopancreas of Aplysia depilans.

Abstract: 1. 1. The existence of different pathways in steroid biosynthesis in the gonad and hepatopancreas and of an alternative pathway from non-steroidal precursors has been studied in Aplysia depilans. 2. 2. Incubation of both tissues with pregnenolone-7α-3H and progesterone-4-14C yielded the following metabolites: progesterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone and cortisol. The ratio 3H/14C for androstenedione is higher in the hepatopancreas. 3. 3. The conversion of mevalonic-2-14C acid to steroid hormones is feeble in both tissues; cholesterol is not found, yet some corticosteroids are formed only from this precursor. 4. 4. Desmosterol-4-14C is converted to many steroids, including cholesterol, but cortisol is formed in a lower concentration than from mevalonic acid and cortisone and deoxycorticosterone are absent. 5. 5. These findings support the view that the metabolic pathway is different in the two tissues studied and that some metabolites are formed through a pathway which does not include C-27 sterols.

Steroidogenesis in vitro in the harp seal (Pagophilus groenlandicus) without and with methyl mercury treatment in vivo.

Abstract: Tissue from a harp seal given methyl mercury at a concentration of 0.25 mg/kg in its diet for 61 days, was highly contaminated with mercury. Over 70% of the mercury in the seal's liver (64.0 p.p.m.) was in the inorganic form indicating a demethylating system in this organ. Most of the mercury in the liver, spleen and kidney of an untreated seal was also in the inorganic form. In contrast, over 75% of the mercury in the adrenals and gonads (14.2 and 13.0 p.p.m., respectively) of the treated seal was methyl mercury. Mercury was not detectable in the gonads and not analyzed in the adrenals of the untreated seal. Biosynthesized (in vitro) cortisol, corticosterone, cortisone, and 11-ketotestosterone were isolated and identified from the adrenal incubations, and delta4-androstene-3,17-dione and testosterone were isolated and identified from ovarian incubations from both untreated and methyl mercury (in vivo) treated seals. The ovaries and adrenals from both seals appeared to be normal under the light microscope. The ovaries from both seals were in the same follicular phase, but in vitro incubations of tissue from these organs indicated that the methyl mercury and treatment caused a marked alteration of steroid biosynthesis in tissue from the treated seal. The altered pattern of steroid biosynthesis was also demonstrated by autoradiography, and it is suggested that this technique could be used as an indicator of incipient contamination by a pollutant.

Fine structure of the gonads of the horse and its functional implications.

Abstract: Light and electron microscopic studies of the gonads of the fetal horse have shown that, in their hypertrophic condition which begins during the 3rd month, the interstitial cells contain large amounts of smooth endoplasmic reticulum, suggesting a secretory activity. Hydroxylating activity which was cytochrome P-450-dependent was observed in the fetal testis and may be involved in steroid biosynthesis.

Changes in fine structure accompanying estrogen-induced tumorigenesis of Leydig cells in the mouse testis.

Abstract: Summary The development of estrogen-induced Leydig cell tumors in cryptorchid BALB/c mice was studied with the electron microscope. Changes in Leydig cell fine structure are apparent by 10 days after the s.c. implantation of a pellet of diethylstilbestrol (DES). The smooth endoplasmic reticulum is diminished, and there is an increase in lipid droplets and free polysomes as compared with untreated cryptorchid controls. These alterations persist as the Leydig cells proliferate to form focal areas of hyperplasia in the interstitial tissue. During this period of proliferation, activated macrophages containing large residual bodies appear among the Leydig cells. If DES treatment is continued for several months, malignant Leydig cell tumors result. They are characterized by a nuclear and cytoplasmic pleomorphism of the Leydig cells and a decreased macrophage population. Virus-like particles are rarely seen within the cells during the period of tumorigenesis. Along with the reduction in smooth endoplasmic reticulum in the Leydig cells after DES treatment, evidence from the literature suggests that there is also a decrease in testosterone biosynthesis. However, it is not clear whether these two effect are correlated, since the level of the microsomal enzymes of steroid biosynthesis may vary independently of either the amount of smooth endoplasmic reticulum or the level of androgen secretion. The increase in lipid droplets seen in Leydig cells after DES treatment suggests the accumulation of precursors from the steroid biosynthetic pathway. The macrophages are thought to represent scavenger cells, rather than a primary tumor cell population. The paucity of virus-like particles within altered Leydig cells implies that formed virus is not a prerequisite for tumorigenesis.

Formation of steroids by the pregnant mare. V. Metabolism of 14C-isopentenylpyrophosphate and 3H-dehydroisoandrosterone injected into the fetus.

Abstract: A mixture of l-14C-isopentenylpyrophosphate and 3H-dehydroisoandrosterone was injected into a horse fetus intramuscularly during laparotomy, after which maternal urine was collected for 4 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolysed and separated into phenolic and neutral fractions. From the phenolic fraction estrone, 17α-estradiol, equilin and equilenin were isolated. Only estrone and 17α-estradiol contained both 3H and 14C, while the ring B unsaturated estrogens contained only 14C. From the neutral fraction 14C-labeled 3β-ydroxy- 5α-pregnan-20-one, 5α-pregnane-3β,20β-diol and 5α-pregnan-3β,20α-diol were isolated. These results demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of isopentenylpyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis reported previously by us is occurring at a point after the formation of isopentenylpyrophosphate and prior to...

Ultrastructural changes of the adrenal cortex in Cushing's syndrome treated with aminoglutethimide (Elipten Ciba)

Abstract: The main ultrastruotural feature of human adrenal cortices following administration of aminoglutethimid (Elipten® Ciba), a steroid biosynthesis blocking agent, is a striking intracellular accumulation of lipids, also seen in the light microscope. The lipids accumulate in the adrenocortical cells but are also stored in the cytoplasm of pericapillary histiocytes. The lipids are present in the adrenocortical cells mostly as rounded liposomes of variable size, whereas those in the histiocytes usually show up as an amorphous debris with abundant myelin figures and cholesterol crystals. In some areas of the adrenal cortex activated histiocytes changing into lipophages may become the prevalent cell. They also take the place of destroyed adrenocortical cells and can form compact cell aggregates of variable size or even columnar strands between neighbouring capillaries, thus resembling columns of adrenocortical cells.

Studies on isolated rat adrenal cells i. continuous flow and batch incubations

Abstract: A procedure for the continuous flow incubation of isolated adrenal cells is described. In this way the advantages of continuous flow incubations of adrenal tissue are combined with those of isolated adrenal cells. Suspensions of isolated adrenal cells were prepared by a modification of the collagenase method. A sigmoid dose-response curve was obtained when these cells were incubated with ACTH in batch incubations. Under these conditions (in the presence of 1 mU ACTH/ml) the corticosterone production rate remained constant during at least 240 min. This production rate was linearly related to the number of cells. Pre-incubation of the cells during 3 h resulted in an increased response to ACTH. In continuous flow incubations without ACTH the corticosterone production was negligible. With 100 mu U ACTH/ml corticosterone production increased sharply after a short lag period. A maximum was reached after 60-75 min followed by a slow decrease. Cells pre-incubated in the continuous flow apparatus had a slightly diminished ACTH response without loss of affinity to ACTH. The continuous flow incubation of isolated adrenal cells offers new possibilities for the dynamic study of steroid biosynthesis in vitro. The method may also be valuable to study processes in a wide variety of other tissues.

Functional morphology of the interrenal and chromaffin cells in the teleosts, Rasbora daniconius (Hamilton), Barbus stigma (Cuv. et Val.) and Channa gachua (Hamilton).

Abstract: The interrenal cells in Rasbora daniconius, Barbus stigma and Channa gachua are mainly found around the postcardinal vein and its major branches in the haemopoietic head-kidney. The chromaffin cells which are identified by the positive chromaffin reaction are found in the walls of the postcardinal vein or dispersed among the interrenal cells. delta5-3beta-HSDH and G-6-PDH activity was observed in the interrenal cells of all three teleosts. The present work indicates that the interrenal cells are capable of steroid biosynthesis and the chromaffin cells contain biologically active catecholamines.

Histochemical localization of Δ5-3β-hydroxysteroid dehydrogenase, glucose-6-phosphate dehydrogenase, and NADH- and NADPH-diaphorase activities in the testis ofRana hexadactyla andCacopus systoma

Abstract: The distribution of Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-HSDH), glucose-6-phosphate dehydrogenase (G6PDH), NADH- and NADPH-diaphorases were localized histochemically in the testis ofRana hexadactyla andCacopus systoma. Dehydroepiandrosterone (DHEA) and pregnenolone were used as the substrates for the demonstration of Δ5-3β-HSDH activity which occurs mainly in the interstitial Leydig cells and also in the columnar Sertoli cells. Both G6PDH and the NADPH-diaphorase show a distribution similar to that of Δ5-3β-HSDH but give intense reaction, whereas the distribution of NADH-diaphorase is ubiquitous. It is concluded that the Leydig cells form the principal site and the Sertoli cells an additional site of steroid biosynthesis in the testis of bothR. hexadactyla andC. systoma.

[Electron microscopic autoradiography of the adrenal cortex following administration of cholesterol-H3].

Abstract: Distribution of labeled cholesterol-H3 and its metabolites in the adrenal cortex cells was investigated by electronmicroscopic autoradiography. The selective uptake of the labels by the mitochondria and lipid vacuoles was demonstrated.

Age-Dependent Sensitivity and Specific Isoenzyme Inhibition of Glucose-6-Phosphate Dehydrogenase by Dehydroepiandrosterone

Abstract: Glucose-6-phosphate dehydrogenase (EC 1.1.1.43) is the rate-limiting enzyme in the hexosemonophosphate pathway and plays an important role in lipogenesis and steroid biosynthesis. The enzyme is inhibited by steroid hormones, as was first reported by Marks and Banks /1/ and by McKerns et al /2/. Levy /3/ found that dehydroepi-androsterone inhibited the NADP — but not the NAD — linked G-6-PDH isolated from mammary glands of lactating rats. Urea, glycerol, high pH and increased temperature were found to reverse the inhibition by dehydroepiandrosterone, suggesting alterations in the three-dimensional structure of the enzyme and the removal of the steroid- binding site from the proximity of the active centre. Human testicular /4/, ovarian /5/ an-d placental /6/ G-6-PDH are also inhibited by different steroid hormones as well as by their derivatives, analogues and conjugates, dehydroepiandrosterone (DHEA) being the most potent inhibitor in vitro. With rat liver G-6-PDH, Lopez and Rene /9/ have shown that at 5.10 -5 M dehydroepiandro sterone uniformly inhibits all four isoenzymes with complete disappearance of band D at the higher concentration of 10 -4 M.