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At least 19 recordsLinked to original sources
PubMed1976

Estrogen biosynthesis and 1beta-hydroxylation using C19 and 19-nor steroid precursors.

(1) In order to study the relationship between aromatization (estrogen biosynthesis) and 1beta-hydroxylation, the effects of a variety of factors on these processes were evaluated. (2) Using the C18 substrate, 4-estrene-3,17-dione, it was found that carbon monoxide, SU-4885, amphenone B, potassium cyanide, 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione inhibited the above transformations significantly and to varying degrees. However, within a given experiment the inhibition of each process was similar. (3) SKF-525A did not inhibit either transformation. In addition, phosphate, Tris and barbital buffers, as well as pH changes from 6.9 to 7.7, had no stimulatory or inhibitory effect on the production of estrogen and 1beta-hydroxy compounds. (4) In contrast, several inhibitors affected the aromatization of C19 and C18 steroids differently. These include carbon monoxide, SU-4885 and amphenone B. (5) When a mixture of 4-[7beta-3Hi1estrene-3,17-dione and 19-[4-14C]nortestosterone were incubated together the former was preferentially converted to estrogen. This preference for the 17-keto steroidal form mimics results observed for C19 substrates. (6) We conclude that while estrogen biosynthesis and 1beta-hydroxylation appear to be mediated by the same enzyme system, the same conclusion cannot be drawn for the aromatization of C19 and C18 substrates.

Buffers↗
PubMed1976

Identification of conjugated estrogen metabolites in dog plasma following administration of estriol-2,4,6,7-3H.

Following the constant infusion of 2,4,6,7-3H-estriol in male dogs for a period of 90 minutes, the radioactive metabolites present in arterial plasma were separated by solvent partition, DEAE-Sephadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives.

Animals↗
PubMed1977

Isolation, synthesis, and biological activity of five metabolites of danazol.

Metabolites of danazol (17 alpha-pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol), an orally effective pituitary gonadotropin inhibitory agent devoid of estrogenic and progestational activites, were isolated from urine of a female subject who had taken danzol orally at a dose of 800 mg/day for 7 days, The metabolites isolated were 17-hydroxy-17alpha-pregn-4-en-20-yn-3-one (11), 17-hydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-3n-20-yn-3-one (5), 17-hydroxy-2-(hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one(7), 6beta,17-dihydroxy-2alpha-(hydroxymethyl)-17alphapregn-4-en-20-yn-3-one(8), and 6beta, 17-dihydroxy-2(hydroxymethyl)-17alphapregna-1,4-dien-20yn-3-one(10). None of these metabolites exhibited pituitary inhibiting activity comparable to danazol.

Animals↗
PubMed2026

Evaluation of metabolic, reproductive, and gut microbiota alterations in a comparative study of different preclinical models of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifaceted, complex metabolic and endocrine disease where gut flora is considered an important factor in causing PCOS. This study aimed to identify a suitable PCOS model that contributes to gut microbial dysbiosis and metabolic and hormonal disturbances. Prepubertal SD rats were administered with normal control (NC), dihydrotestosterone (DHT), DHT with fructose (F), DHT+ high fat diet (HFD) for 91 days, dehydroepiandrosterone (DHEA), DHEA with fructose, DHEA with HFD for 30 days, sodium valproate (SV), sodium valproate with fructose, and sodium valproate with HFD for 21 days. The estrous cycles were assessed over this timeframe. At the end of the experiment, superoxide dismutase and uterine and ovarian morphology were evaluated, along with hormone levels, lipid profiles, and 16S rRNA genomic sequencing. All models exhibited PCOS characteristics, including hormonal imbalances, insulin resistance (p ≤ .001), multiple follicular cysts on ultrasonography, and histological alterations. Gut microbial dysbiosis was observed across all PCOS-induced groups; however, the DHT alone group showed more pronounced alterations in microbial composition than the other experimental groups. Specifically, the DHT alone group exhibited reduced abundance of Firmicutes and increased abundance of Proteobacteria. Among the evaluated models, the DHT-only model showed more pronounced metabolic, hormonal, reproductive, and gut microbial alterations and may serve as a suitable model for PCOS research.

Animals↗
PubMed1979

Kinetics of tryptophan transport across the blood-brain barrier.

The transport of tryptophan across the blood-brain barrier in vivo has been analyzed kinetically to assess the influence upon it not only of the concentration of tryptophan in the blood plasma, but also of the inhibitory effect of fourteen other amino acids normally present in the circulation. The transport of tryptophan into the brain conforms to the equations of enzyme kinetics with competitive inhibition, provided appropriate modifications are made to take account of a non-saturable component (possibly passive diffusion) in the transport, and of the normal presence in the blood of other amino acids which act as competitive inhibitors. The inhibitor constant has been evaluated for each amino acid and in many cases it corresponds fairly closely with the Michaelis saturation constant for that amino acid, suggesting that tryptophan and these inhibitors share a common transport carrier. The implications of the kinetic analysis are considered for hormonal and metabolic disturbances which change the proportions of amino acids in the blood. The effect of an increase in competitive inhibition due to raised levels of amino acids is to make the tryptophan influx more directly dependent upon the level of tryptophan in the blood.

Animals↗
PubMed2026

Genome-Wide Characterization of β-Glucosidase (TaBGLU) Genes in Bread Wheat and Their Expression Under Drought, Cold, and Combined Stress.

Glycoside hydrolase 1 (GH1) β-glucosidases were known to activate hormone conjugates and defense metabolites, yet their genomic organization and stress-response dynamics in wheat remained incompletely defined. We therefore performed an integrated characterization of TaBGLUs spanning phylogeny, gene structure and conserved motifs, subcellular localization, promoter cis-elements, Gene Ontology enrichment, protein-protein interaction networks, and targeted expression profiling. Wheat TaBGLUs partitioned into well-supported clades that shared canonical GH1 catalytic residues and a largely conserved motif scaffold. Subcellular localization predictions indicated predominant nuclear and chloroplast targeting, with a smaller cohort directed to secretory or endomembrane compartments. Promoters were enriched for light-responsive, hormone-related (ABA, JA/SA, auxin, GA) and stress-associated (MYB/WRKY, heat, low temperature) cis-elements, and functional annotations were consistent with roles in carbohydrate and cell-wall metabolism, hormone homeostasis, and defense. Network analysis revealed a densely connected TaBGLU submodule embedded within broader carbohydrate and defense interaction networks, suggesting coordinated or cooperative functions. Expression profiling under cold, drought, and combined drought and cold demonstrated broad stress inducibility, with early activation detected by 6 h, cold-responsive maxima typically at 12 h, drought-responsive peaks predominating at 24 h, and combined stress eliciting both earlier and more sustained expression maxima between 12-24 h. Representative strongly responsive genes included TaBGLU20, TaBGLU44, TaBGLU6, and TaBGLU23, which showed pronounced late induction under combined stress, TaBGLU30, which exhibited an earlier combined-stress peak, and TaBGLU12, which displayed a marked late drought-specific response. Taken together, this integrated genomic, regulatory, and expression atlas refined the wheat BGLU repertoire relative to previous gene model inventories, highlighted candidate TaBGLUs with central network positions and strong stress inducibility, and provided concrete entry points for functional validation and breeding for improved stress resilience.

Triticum↗
PubMed1975

[Effect of cyclic AMP and Ca++ on steroidogenesis by rat adrenal mitochondrial fraction. Studies on the mechanism of ACTH action (I) (author's transl)].

Despite the accumulation of a number of studies, the mechanism of action of ACTH remains to be clarified. Although it is now clear that cyclic AMP acts as a intracellular mediator of ACTH action, the mechanism of its action on the stimulation of steroidogenesis is not known. The present studies were carried out to test the hypothesis that cyclic AMP might act directly on adrenal mitochondrial fraction to stimulate the metabolism of cholesterol to pregnenolone and progesterone, and to determine whether Ca++ might modulate the action of cyclic AMP. Adrenal mitochondria were obtained from male Sprague-Dawley rats pretreated with dexamethasone. Steroidogenesis by the mitochondrial fraction from cholesterol-4-14C (0.2-0.25 muCi, 3.6-4.5 mmumole/sample) were measured in a system containing 20 mM tris-HCl buffer (pH 7.4), 11.5 mM NaCl, 15.4 mM KCl, 70 mM sucrose, 10 mM sodium succinate and mitochondrial fraction (0.16-0.22 mg protein/sample). Incubations were performed at 37 degrees C, with shaking, in the presence or absence of cyclic AMP, cyclic GMP and cycloheximide. After incubation, the medium was extracted with chloroform, and the extracts were analyzed by thin-layer chromatography. And the radioactivity of the separated steroids was measured. The products from cholesterol-4-14C were mainly pregnenolone and progesterone, and the other products were almost negligible. Cyclic AMP effected the formation of pregnenolone and progesterone by mitochondria. Cyclic AMP exerted its effect even at low concentrations (5 X 10(-6) approximately 5 X 10(-5)M), which was presumably near the intracellular level. On the other hand, cyclic GMP (5 X 10(-5) M) failed to enhance steroidogenesis. The effect of Ca++ on the action of various concentrations (5 X 10(-6) approximately 3 X 10(-3) M) of cyclic AMP was also clearly demonstrated. Addition of Ca++ (1 mM) to the incubation medium intensified the stimulatory effect of cyclic AMP in each concentration. And in the presence of Ca++, the most effective level of cyclic AMP was shifted from 5 X 10(-4) approximately 3 X 10(-3)M to the lower concentration (5 X 10(-5)M). In addition, cyclic AMP action was modified by the changes in the concentration of Ca++ in the medium. At concentration of 10(-6) M of Ca++, steroid formation of mitochondria was maximally activated by cyclic AMP. These observations suggest that cyclic AMP enhances steroidogenesis by acting directly on adrenal mitochondria to stimulate pregnenolone and progesterone formation from cholesterol, and that Ca++ plays a significant role in its action.

Adrenal Glands↗
PubMed1977

[Studies on the excretion of estrogen in cows following oral and percutaneous (pour-on) administration of chlormadinone acetate].

The oestrogen levels were assessed in 180 urine samples taken from 20 cows. The animals had received over 15 days 40 mg one-per-cent oily solution of chloromadinone acetate. The solution had been applied orally or by pour-on methods. The curves of oestrogen excretion were identical for both methods of application, both during and after completed administration. In other words, the effect obtainable from pour-on application is just as good as that obtainable from oral administration.

Administration, Oral↗
PubMed2026

Genome-wide identification and expression analysis of the UGT gene family in honeysuckle.

BACKGROUND: The UGT gene family plays critical roles in regulating plant growth, development, stress responses, and secondary metabolite synthesis. Although UGT proteins have been studied in numerous plant species, research on the UGT family in honeysuckle (Lonicera japonica Thunb.) remains limited. RESULTS: In this study, a comprehensive genome-wide analysis of the UGT gene family was performed in honeysuckle. A total of 224 unique LjUGT genes were identified and classified into 21 distinct subfamilies (T71-T92 without T77) based on the phylogenetic analysis. These genes were unevenly distributed on the 9 chromosomes. Eighteen segmental duplication events and 61 tandem duplications were identified, of which only 3 were positive selection. Integrated analysis of promoter cis-acting elements, transcription factors, targeted miRNAs, and interacting proteins suggested that the expression and function of the LjUGT genes may be regulated by transcription factors and proteins through binding to the various binding sites and cis-acting elements, thereby putatively participating in diverse biological processes, including hormone signaling, stress response, and metabolism. The expression pattern analysis of LjUGTs in different tissues and under stress conditions indicated that Lj2A1135G32, Lj5A236T61, Lj6A350T83, and Lj7A737T47 emerged as candidate genes potentially associated with development, 46 genes showed expression changes under all 6 abiotic stresses, suggesting broad stress responsiveness. Additionally, there 7 genes were identified as candidate hub genes that may correlate with the low temperature stress tolerance in honeysuckle according to the WGCNA results, and further verification by qRT-PCR confirmed that Lj4A99G61 and Lj9A591T82 can be regarded as key candidate genes for in-depth research. CONCLUSIONS: This study systematically identified 224 LjUGT genes in honeysuckle for the first time and characterized their physicochemical properties, phylogenetic relationship, and expression patterns. These findings provide a foundational resource for hypothesis-driven investigations into the functions and action mechanisms of LjUGTs.

Lonicera↗
PubMed1976

Estrogens in maternal plasma following intraamniotic injection of (3H)-dehydroepiandrosterone-sulfate in midpregnancy.

In 4 patients with normal pregnancies between the 18th and 20th week of gestation (3H7alpha)-dehydroepiandrosterone-sulfate ([H]-DHEA-S) was injected intraamniotically. Maternal venous blood was drawn before and at regular intervals for 240 minutes after DHEA-injection. Thereafter, legal abortion was performed by intraamniotic instillation of prostaglandine. The conjugated steroids were hydrolyzed enzymatically and the total steroids were isolated and identified. The following labelled metabolites were determined quantitatively: Estriol (e3, estradiol-17beta (E2-17beta), estrone(E1), 16alpha-hydroxy-estrone, (16alpha-OH-DHEA), ALPHA4-androstenedione (AD) and testosterone (T). The maximal increase of all estrogen fractions in matermal plasma occurred 120-180min after intraamniotic injection of the precursor. The most prominent rise of the C18-steroids could be shown for estriol. 60-70% of all metabolites were C16-hydroxylated.

Amnion↗
PubMed1979

[Viable cells from human renal cell carcinoma: isolation procedure and analysis of hormone sensitivity (author's transl)].

An enzymatic procedure for the isolation of metabolically active tumour cells from human renal cell carcinoma is described. The cells were suspended by a multistep incubation procedure of the tissue in the presence of collagenase (10 mg enzyme/g tumour wet weight) dissolved in a calcium-free buffer solution. About 90% of the isolated tumour cells were viable, as judged by routine trypan blue staining. Electron microscopic examination revealed tumour cells in various stages of dedifferentiation. The cells had retained their capability of protein synthesis. In short term experiments the effects of 17 beta-oestradiol and progesterone on the incorporation of [U - C] L-leucine into cellular proteins was studied; Progesterone was found to exhibit a slight tumour antianabolic or catabolic action. A 17 beta-oestradiol-dependent modulation of the rates of protein synthesis was not observed.

Adenocarcinoma↗
PubMed1976

Delta5-androstenediol: kinetics of metabolism and binding to plasma proteins in normal men and women.

Using the constant fusion and single injection technique the metabolic clearance rates (mean +/- SEM) for delta5-androstene-3beta, 17beta-diol (delta5-idol) were measured for 19 normal men (1311 +/- 67 1/24 h) and 10 normal women (858 +/- 63 1/24 h). The constant infusion technique yielded values for the conversation ratios for the transformation of delta5-diol to several products: dehydroepiandrosterone (DHEA)/delta5-diol of 0.06+/-0.01 for men and 0.05 +/- 0.01 for women, of delta5-diol sulfate/delta5-diol of 0.45 +/- 0.04 for men and 0.52 +/- 0.03 for women and of DHEA sulfate/delta5-diol of 5.53 +/- 0.26 for men and 5.02 +/- 0.42 for women. The single injection technique yielded rate constants (units) and volumes of distribution (liters) for delta5-diol; Ki = 34.3 +/- 4.3 for men and 35.0 +/- 3.9 for women, K2 = 63.7 +/- 4.1 for men and 75.1 +/- 4.2 for women, V1 = 23.1 +/- 3.2 for men and 11.9 +/- 2.3 for women, V2 = 14.8 +/- 3.7 for men and 9.2 +/- 3.2 for women. The mean delta5-diol plasma concentration was 1.08 +/- 0.10 ng/ml for 12 men and 1.17 +/- 0.16 ng/ml for 9 women. (he calculated blood production rates for delta5-diol were 1357 +/- 117 mug/24 h for 12 men and 969 +/- 131 mug/24 h for 9 women. The per cent binding (equilibrium dialysis) was higher for women (94.9 +/- 0.3) than for men (93.0 +/- 0.2). Paper electrophoresis showed that significant fractions of 3H-delta5-diol migrated with both the beta-globulin and albumin fractions. Estrogen administration to two normal men increased the per cent binding of delta5-diol to plasma proteins and decreased the metabolic clearance rate towards the values found for normal women.

Adult↗
PubMed1975

Quantitative aspects of hormone-receptor interactions of high affinity. Effect of receptor concentration and measurement of dissociation constants of labeled and unlabeled hormones.

It is demonstrated that because of limitations in the magnitude of the specific activity of radiolabeled hormone derivatives, direct binding studies of hormone-receptor interactions of high affinity (10(-9) -10(-11) M, depending on whether 3H- or 123I-labeled hormones are used) will be subject to artifactual distortions due to the need to utilize high concentrations of the receptor. If the concentration of the receptor is not ten times lower than the true affinity constant, the apparent dissociation constant obtained from direct concentration binding curves will vary as a linear function of the receptor concentration. In addition, at high receptor concentrations saturability becomes difficult to demonstrate experimentally and the binding data yield apparently non-hyperbolic, sigmoidal curves which can be mistakenly interpreted to depict cooperative interactions. Similar artifacts related to receptor concentration are predicted for measurements of the hormone concentration dependence of biological proce-ses (e.g. activation of adenylate cyclase, transport processes, etc.). Methods for detecting these effects, and correctly measuring affinities for labeled and unlabeled hormones under these conditions, are described. The implications for measuring the binding properties of hormone-receptor interactions are discussed, especially in reference to studies of the comparative analysis of receptor function in altered metabolic states and to studies relating the biological and binding properties of hormones.

Binding Sites↗
PubMed1977

Effects of progesterone on some enzymes of fat and carbohydrate metabolism in rat liver.

The known effect of progesterone on carbohydrate metabolism prompted a study of some of the hepatic "lipogenic" and "gluconeogenic" enzymes in rats treated with progesterone. Several enzymes providing lipid precursors (phosphofructokinase, malic enzyme, glucose-6-phosphate dehydrogenase, and citrate cleavage enzyme) showed increased specific activity. These changes may represent insulin effects. Specific activity of phosphoenolpyruvate carboxykinase, usually associated with control of gluconeogenesis, was also increased. The latter is compatible with increased capability for glycogenesis, which is recognized as a progesterone effect.

ATP Citrate (pro-S)-Lyase↗