Showing papers on "Steroid biosynthesis published in 1976"

Control of oestrogen production in human pregnancy: effect of trophic hormones on steroid biosynthesis by the foetal adrenal gland in vitro.

Abstract: [14C]Acetate was incorporated into dehydroepiandrosterone, pregnenolone and their sulphates and into cholesterol during incubations of adrenal tissue from three human foetuses of 10-18 weeks of gestation. No incorporation of [14C]acetate into cortisol or other 4-en-3-oxo steroids could be demonstrated. Porcine ACTH stimulated the incorporation of [14C]acetate into both dehydroepiandrosterone sulphate and cholesterol when added to incubations of adrenal tissue from foetuses of 18 weeks gestation. Such an effect was not observed with tissue from a 10-week-old foetus. Stimulation of steroid biosynthesis from [14C]acetate was also achieved by addition of human growth hormone chorionic somato-mammotrophin. These trophic hormones may therefore play some part in regulating the provision of precursors for oestrogen biosynthesis in pregnancy.

Familial true hermaphorodism in three siblings: plasma hormonal profile and in vitro steroid biosynthesis in gonadal structures.

Abstract: The in vitro biosynthesis of estrogens and androgens by gonadal tissues of the ovotestes was studied in three siblings with familial true hermaphrodism and correlated with daily steroid and gonadotropin plasma levels. The probands were 15, 13, and 11 years old with normal male phenotype and external genitalia, grade III hypospadias, bilateral scrotal ovotestes, gynecomastia, and no uterus or fallopian tubes. Their karyotypes were 46XX both in peripheral lymphocytes and in gonadal fibroblasts, and no Y chromosome fluorescence was observed. A fusiform biopsy of each gonad was obtained, and the testicular and ovarian structures were excised and incubated for five days at 37 C with 3.8 muCi of 7alpha3H dehydroepiandrosterone, in Eagle's growth media, 95% O2 and 5% CO2. After standard procedures, four extractions with methylene chloride were performed, and the residue was assayed using Sephadex LH no. 20 chromatography. Testosterone (T), delta4androstenedione (delta 4), 5alphadehydrotestosterone (5alphaDHT), estrone (E1), estradiol-17 beta (E2) and estriol (E3) were measured. Also, during 16 consecutive days daily venous samples were obtained, and FSH, LH, E2, progesterone (P), and testosterone (T) were determined. The predominant steroids formed in vitro were estrogens, mainly E1 by either the testicular or ovarian structures. In the 11-year-old subject, the ovotestes were less active than in his oldest siblings. The patterns of androgen production showed that T was the principal androgen formed, followed by delta4 and minimal amounts of 5alphaDHT. The daily plasma hormonal profile resembled more closely a female pattern, specially in the 15 and 13-year-old patients. It is suggested that the ovotestes of these siblings had the enzymatic mechanisms necessary for estrogen and androgen biosynthesis, mainly E1 and T using a preferential metabolic pathway via androstenedione. Furthermore, it seems that the testicular structures had a greater capability to synthesize estrogens than the ovary.

Steroid biosynthesis in the whelk, Buccinum undatum

Abstract: 1. 1. The sterol synthesising capability of the marine gastropod Buccinum undatum was investigated using [3H]sterol precursors. 2. 2. Lanosterol, but not cycloartenol was bioconverted to cholesterol. 3. 3. 24-Methylenecholesterol and β-sitosterol (Δ5-sterols) were both dealkylated to cholesterol. 4. 4. Chondrillasterol, a Δ7 sterol was not converted to cholesterol, suggesting that B. undatum does not have the enzymes required for rearrangement of the nuclear double bond.

The role of cytochrome P-450 in the regulation of steroid biosynthesis.

Abstract: A mitochondrial cytochrome P-450 catalyzes the conversion of cholesterol to pregnenolone in the various steroid-forming organs: pregnenolone is converted to the steroid hormones secreted by these organs. The conversion of cholesterol to pregnenolone is commonly called side-chain cleavage (Figure 1). Side-chain cleavage appears to determine the rate of steroid biosynthesis so that the role of P-450 in that reaction is important in considering the regulation steroid production in the whole animal (1–3).

Estrogenic hormones‐general considerations

Abstract: General considerations of estrogenic hormones are reported. Biosynthesis (the estrogen biosynthesis in the fetoplacental unit; the transformation of estrogenic hormones) orally active estrogens and estrogenic effects (estrogens pituitary and hypothalamus; estrogen and cancer; estrogens as therapeutics) are discussed. Simplified schemes of the biosynthesis of the biologically active human steroids of the aromatization of ring A and of the steroid biosynthesis of the fetoplacental unit are included.

Gas chromatography of steroids and its clinical applications, including loading tests with deuterated compounds1

Abstract: Glass capillary columns have been used successfully for the determination of steroids. They are especially suitable for the recognition of the identity of unknown compounds, using a combination of gas chromatography–mass spectrometry (GC–MS). The practicability of the method is demonstrated by studies of urinary steroids in a patient with 21-hydroxylase deficiency, in a patient with a special 11β-hydroxylase deficiency and in a patient with an obscure enzyme defect in steroid biosynthesis, probably a lipoid adrenal hyperplasia. Performing the metyrapone test, tetrahydro-S (THS) determination with glass capillary columns allows a specific evaluation of hypothalamic-pituitary-adrenal function (normally 100 to 500 fold increase of THS). The investigation of steroid metabolism using deuterated precursors (oral and intravenous loading tests) has been tried with deuterated pregnenolone and progesterone. Only urinary pregnanediol, 5α-pregnanediol and another unknown steroid were found to be deuterated. An oral loading test with deuterated cholesterol showed no deuteration of urinary steroids except cholesterol, cholest-4-en-3-one and a side chain monohydroxylated cholest-4-en-3-one.

Transient intermediates in steroidogenesis

Abstract: Analogs of cholesterol and pregnenolone have been synthesized and tested as hormonal precursors. Homologues of cholesterol in which C-22 is completely substituted (e.g. (20R-20-t-butyl)-5-pregnene-3β,20 diol, (20R)-20-(phenyl)-5-pregnene-3β,20 diol) were incubated with acetone powders of adrenal glands and appropriate cofactors and each was converted into pregnenolone. The side-chain fragment of the aryl derivative formed biosynthetically in this reaction was identified as phenol. In addition, another fragment, acetophenone, was isolated but the C19-steroidal product of this unusual pathway has not yet been identified. In a comparable manner, the conversion of C21-steroids into C19-androgens was studied. An analog of pregnenolone which was devoid of oxygen at C-20, 5-pregnene-3β-ol, was synthesized and when incubated with testicular microsomes was converted into testosterone. These results suggest that the true intermediates in steroid biosynthesis may not be isolable hydroxylated compounds as traditionally conceived, but rather enzyme bound, transient, reactive species.

Effect of prostaglandins on steroid biosynthesis

Abstract: The role of prostaglandins (PGs) as agents interfering in steroidogenesis is contradictory in vivo and in vitro. PGs may affect steroid production by (1) altered utilization of cholesterol via changes in esterase or synthetase enzyme levels, (2) by affecting levels of adenyl cyclase enzyme system and cAMP, (3) by increasing 20α-hydroxysteroid dehydrogenase levels. PGs may also indirectly influence steroid synthesis by modulating the secretion of gonadotropins. The more completely investigated action of PGs has been that of induced luteolysis on the corpus luteum of the luteal phase and of pregnancy. The in vivo luteolytic properties of PGF2α have been, on occasion, contradicted by in vitro studies in which progesterone synthesis has been stimulated. The mechanism of action of PGs in luteolysis seems to be that of increasing production of inactive progestins. Other roles of PGs, such as stimulation of cAMP, estrogen production and testosterone secretion, are still a matter of continuous investigation. In bovines, PGF2α increases release of this C19 steroid, while in the mouse, the peripheral testosterone levels are reduced, probably by inhibition of cholesterol esterase.