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PubMedDate not supplied

Effect of sodium butyrate on human breast cancer cell lines.

We have investigated the effects exerted by sodium butyrate (NaBu) on the growth and cell cycle perturbations of four human breast cancer cell lines (MCF7, T47D, MDA-MB231 and BT20) with different steroid receptor profiles. Moreover, since one of the supposed mechanisms of action for NaBu activity involves the induction of apoptosis, we have studied the effects of NaBu on DNA fragmentation by agarose gel electrophoresis and flow cytometry. In all investigated cell lines, NaBu exerted a time- and dose-dependent inhibition of growth and caused a maximum inhibitory effect (85% to 90%) at the concentration of 2.5 mM. The inhibition was already evident after 3 days of treatment. The antiproliferative effect of NaBu was associated with a persistent block of cells in the G2M phase. The block was associated with apoptosis only in oestrogen-receptor positive cell lines. The inhibiting effect of NaBu in hormone-dependent and independent cell lines and its ability to induce apoptosis through a cell cycle perturbation in hormone-dependent cell lines may have important implications in the treatment of human tumours including breast cancer.

Antineoplastic Agents↗
PubMed1996

Temporal aspects of ovarian follicular growth and steroidogenesis following exogenous follicle-stimulating hormone in Angus heifers.

Ultrasonography and endocrine assay techniques were used to monitor structural and hormonal alterations made by the ovary in response to the biological actions of pituitary-derived follicle-stimulating hormone (FSH-P). Angus heifers (n = 36) were allotted to receive injections (twice per day) of either FSH-P (up to a total of 28 mg over a maximum of 4 days beginning on Day 10 of a synchronized estrous cycle) or saline in order to quantify temporal relationships among follicle growth and steroid hormone profiles. Transrectal ultrasonography was utilized at 12-h intervals to monitor and record follicle growth. Plasma was collected every 12 h for the first 48 h of the experiment and then every 6 h for the remainder of the experiment. At 48 and 60 h after the onset of treatments, prostaglandin F2 alpha (PGF2 alpha; 25 mg) was administered (i.m.). FSH-treated heifers (n = 6 at each time) were terminated at 24, 48, 72 and 96 h following the onset of treatment. Saline-treated heifers were terminated at 24 and 96 h (n = 6 at each time). After ovaries were obtained, follicular number and size were recorded and follicular fluid (FF) was collected. Plasma concentration of progesterone (P) and estradiol (E2) and FF concentration of P, E2, estrone, testosterone and androstenedione were determined by radioimmunoassays. Plasma concentration of E2 increased (P < 0.05) within 36 h of initiation of FSH treatment. Plasma P decreased (P < 0.0001) by 12 h post-PGF2 alpha. Ultrasonographic examination revealed a significant decrease in the number of small follicles by 48 h, whereas the number of medium follicles increased (P < 0.05) by 60 h after the initiation of FSH treatment. The number of large follicles (LF > or = 10 mm diameter) increased (P < 0.01) over the course of the experiment. The total number of ovarian follicles (TF) 24 h after the start of FSH treatment was correlated (r = 0.99; P < 0.0001) with the number of small follicles (SF < or = 5 mm). At 72 h after the onset of FSH treatment, the number of medium follicles (i.e. 6-9 mm) was correlated with TF (r = 0.97; P < 0.0001). Estradiol was the predominant FF steroid. Follicular fluid E2 was greatest in follicles at 72 h after FSH treatment. Follicular fluid E2 and plasma E2 were positively correlated (r = 0.66; P < 0.001). Follicular aromatase activity was estimated by evaluating the ratio of FF estrogens (E) to androgens (A). Elevated aromatase activity (E:A ratio > 1.0) was detected in 196 of 206 follicles. The estrogen to progesterone ratio was used as an estimate of follicle viability. Eighty-five percent of the follicles were estimated to be viable (E:P ratio > 1.0). The peak E:A ratio in LF preceded by 24 h the peak concentration in FF E2 and plasma E2. In MF and SF the E:A ratio increased by 72 h. Enhancement of ovarian follicular growth (i.e. increased number and size of follicles; increased steroidogenesis) by exogenous, pituitary-derived FSH is characterized by (1) increased activity of aromatase, and (2) accumulation of FF E2, events which temporally preceded the increase in plasma concentration of E2. These observations will aid efforts to incorporate recombinant bovine FSH and somatotropin in an effort to develop more predictable superstimulation and ovulation induction protocols.

Animals↗
PubMed1986

Steroid binding to feather follicles in the chicken.

Steroid binding profiles in chicken feather follicles were studied in vitro. Progesterone and promegestone were bound specifically with high affinity (dissociation constant = 7.79 nmol/l in females and 2.0 nmol/l in males) and with low capacity to the high-speed supernatant fraction (cytosol) of homogenized feather follicles. The number of progestin-binding sites was significantly (P less than 0.01) higher in females than in males (1.35 +/- 0.07 (mean +/- S.D.) vs 0.605 +/- 0.15 pmol/mg protein). Significant cross-competition was observed between progestins and glucocorticoids for the binding sites. The heat-activated progestin-receptor complexes bound specifically to DNA-cellulose in vitro. The DNA-cellulose binding was 36.6% of the total specific binding. The presence of progestin-binding sites in the feather follicles implies a direct action of progesterone in this structure, which may be an important factor in the regulation of moulting. The lack of oestrogen binding to the cytosol prepared from the feather follicles suggests different regulation of progestin receptors in different target organs.

Animals↗
PubMed1999

Identification of selective mechanism-based inactivators of cytochromes P-450 2B4 and 2B5, and determination of the molecular basis for differential susceptibility.

Rabbit cytochromes P-450 (P-450) 2B4 and 2B5 differ by only 12 amino acid residues yet they exhibit unique steroid hydroxylation profiles. Previous studies have led to the identification of active site residues that are determinants of these specificities. In this study, mechanism-based inactivators were identified that discriminate between the closely related 2B4 and 2B5 enzymes. A previously characterized inhibitor, 2-ethynylnaphthalene (2EN), was found to be selective for 2B4 inactivation. As inhibitor metabolism and the partition ratio affect susceptibility, molecular dynamics simulations were performed to assess the stability of the productive binding orientation of 2EN within 2B4 and 2B5 three-dimensional models. Although 2EN was stable within the 2B4 model, it exhibited substantial movement away from the heme moiety in the 2B5 model. However, heterologously expressed 2B5 was found to catalyze the oxidation of 2EN to the stable product 2-naphthylacetic acid. Thus, the increased mobility of 2EN may result in reduced susceptibility of 2B5 by increasing the probability that the reactive ketene intermediate hydrolyzes with water instead of reacting with active site residues. Another compound, 1-adamantyl propargyl ether (1APE), selectively inactivated 2B5. The structural basis for 2EN and 1APE susceptibility was assessed using active site mutants. Interconversion of 2EN susceptibility was observed for 2B4 or 2B5 mutants containing a single alteration at residue 363. Single substitutions in 2B4 also conferred susceptibility to 1APE; however, multiple alterations were required to reduce the susceptibility of 2B5. These alterations may influence inhibitor susceptibility by affecting the stability of the productive binding orientation.

Adamantane↗
PubMed2002

Estrogen receptor-alpha and neural circuits to the spinal cord during pregnancy.

Estrogen receptor immunoreactivity and mRNAs are present in spinal cord neurons in locations that are associated with sensory and autonomic innervation of female reproductive organs. The present study was undertaken to examine the expression of estrogen receptor-alpha in the spinal cord during different stages of pregnancy and to determine whether estrogen receptor-alpha-expressing neurons are related to uterine afferent nerves bringing information to the spinal cord at parturition. Immunohistochemistry showed estrogen receptor-alpha-immunoreactive neurons in the dorsal one-half of the spinal cord, i.e., dorsal horn, dorsal intermediate gray areas (dorsal commissural nucleus), and around the central canal and sacral parasympathetic autonomic nucleus of the lumbosacral spinal cord. Neurons in these areas corresponded topographically to the distribution of central processes of visceral primary afferent neurons (e.g., containing calcitonin gene-related peptide and substance P) that innervate and activate second-order spinal cord neurons (evidenced by their expression of Fos) at parturition. Western blots showed that estrogen receptor-alpha increases in the spinal cord, with a peak at day 20 of gestation, followed by a slight decrease by 2 days postpartum. These studies show that estrogen receptor-alpha is expressed by neurons in autonomic and sensory areas of the lumbosacral spinal cord that have connections with the female reproductive system and that the level of estrogen receptor-alpha changes over the course of pregnancy, which may follow profiles of steroid hormones. Many of these neurons may be involved in processing information related to reproductive organ function, changes during pregnancy, and relays to other CNS centers.

Animals↗
PubMed1994

Immunocytochemical comparison of cultured normal epithelial prostatic cells with prostatic tissue sections.

By analyzing a culture system of human prostatic epithelial cells (HPEC) and human prostatic fibroblasts (HPF) for expression of several determinants by immunocytochemistry, we have shown that long-term cultures are able to preserve the phenotypic characteristics of the normal tissue from which they are derived. The cytoskeletal elements, prostate-specific proteins, and steroid receptor profiles were compared to those of prostatic epithelium and stroma in situ. When cultured in low serum and low calcium medium, the adult HPEC grew as two layers of cells, the upper one of which retained the differentiation characteristics observed in the luminal fraction of normal prostatic epithelium. This cell type is the likely origin of prostatic neoplasia, with expression of CK8, 18, and 19 but not CK14. Androgen receptors, prostatic-specific antigen, and prostatic acid phosphatase are also expressed in vitro but at lower level than in situ. The lower cell layer expressed most of the same determinants but at a much lower level, suggestive of a stem-cell type. The HPF cultured in RPMI serum supplemented media retained the stromal pattern of the cells observed in situ. Culture systems which conserve the characteristics of their normal counterparts in vivo should provide useful models for studying in vitro genetic and epigenetic factors associated with differentiation and proliferation, but also with tumorigenic progression in the prostatic gland.

Biomarkers↗
PubMed2000

Profiles of gonadal development, sex steroids, aromatase activity, and gonadotropin II in the controlled sex change of protandrous black porgy, Acanthopagrus schlegeli Bleeker.

The objectives of the present study were to investigate the effects of oral administration of estradiol-17 beta (E(2)) on the sex steroids and gonadotropin II (GTH II) in plasma, aromatase activity in gonad and brain, and sex change in protandrous black porgy, Acanthopagus schlegeli Bleeker. Two-year-old black porgy were divided into two groups, one fed a control diet and the other a diet mixed with E(2) (4.0 mg/kg feed) for 7 months. Significantly higher GSI was observed in the E(2) group. Fish treated with E(2) showed complete suppression of spermatogenesis and spermiation and induced sex change with vitellogenic oocytes and large primary oocytes. Lower levels of plasma 11-ketotestosterone and higher levels of plasma vitellogenin were shown in the E(2) group. Higher gonadal aromatase activity in concordance with elevated plasma levels of GTH II was observed in the E(2) group. The highest aromatase activity in the forebrain in the control group was observed in January. Higher aromatase activity in forebrain, midbrain, and hindbrain was also detected in the E(2) group than the control group. The change of aromatase activity in brain was more susceptible than that in gonad. The data showed that the increase of plasma GTH II levels and gonadal aromatase activity may be important to the controlled sex change by administration in black porgy.

Animals↗
PubMed2003

Elevated serum concentrations of androgens in women with pregnancy-induced hypertension.

Alterations of steroid hormone profiles have been suggested to be involved in the pathophysiology of pregnancy-induced hypertension (PIH). The aim of our study was first to investigate serum concentrations of testosterone, dihydrotestosterone, androstenedione and dehydroepiandrostenedione sulfate in women with PIH and normotensive pregnant women and secondly to evaluate an association between elevated serum concentrations of androgens and the development of severe disease. Serum concentrations of androgens were measured in 40 patients with PIH and 40 normotensive pregnant women, matched for gestational age, determined by enzyme linked immunosorbent assay. Multivariate logistic regression models were used to analyze the influence of elevated serum concentrations of androgens on the occurrence of PIH and the development of severe disease. The median serum concentrations of androstenedione and testosterone were significantly elevated in women with PIH compared to controls (6.3 and 5.0 ng/ml, 1.8 and 1.1 ng/ml, p = 0.005 and p = 0.04, respectively). The difference between the median serum concentrations of dihydrotestosterone and dehydroepiandrostenedione sulfate in women with PIH and controls was not significant. Elevated serum concentrations of androstenedione revealed a significant influence on the odds of presenting with PIH (p = 0.043) and were significantly associated with the development of severe disease (p = 0.014). Women with PIH have elevated serum concentrations of androstenedione and testosterone. Moreover, elevated serum concentrations of androstenedione are associated with development of severe disease.

Adult↗
PubMed2026

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug&#xa0;(NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article↗
PubMed1986

Histologic and hormonal documentation of the luteinized unruptured follicle syndrome.

Histologic and hormonal documentation of a luteinized unruptured follicle that occurred during a spontaneous menstrual cycle in a rhesus monkey is presented. Frequent (every 2 hours) blood sampling to assess midcycle hormonal dynamics in the monkey with the luteinized unruptured follicle and in five monkeys with an ovulatory stigma revealed significant aberrations in the gonadotropin and steroid hormone profiles associated with a luteinized unruptured follicle. Although the midcycle 17 beta-estradiol surge was normal, the monkey with the luteinized unruptured follicle demonstrated (1) blunted midcycle bioassayable luteinizing hormone, immunoassayable luteinizing hormone, and follicle-stimulating hormone surges; (2) absence of disparity in the bioassayable luteinizing hormone: immunoassayable luteinizing hormone ratio during the gonadotropin surge; (3) absence of progesterone and 17 alpha-hydroxyprogesterone secretion during the gonadotropin surge; and (4) delayed and blunted rise in progesterone and 17 alpha-hydroxyprogesterone after the gonadotropin surge. These findings suggest that an impaired luteinizing hormone surge, perhaps mediated by insufficient midcycle progestin secretion, is one possible cause of the luteinized unruptured follicle syndrome.

17-alpha-Hydroxyprogesterone↗
PubMed1983

A comparison of the female reproductive cycles of autumn-spawning and winter-spawning strains of rainbow trout (Salmo gairdneri Richardson).

Annual changes in the plasma concentration of testosterone, 17 beta-estradiol, 17 alpha-hydroxy-20 beta-dihydroprogesterone, vitellogenin, and gonadotrophin were monitored by radioimmunoassay in females of autumn- and winter-spawning strains of rainbow trout. The annual profile of steroids and of vitellogenin, and the relationships between these parameters, were similar in the two strains, except that most changes occurred 2 months later in the winter-spawning strain than they did in the autumn-spawning strain. The times during which most fish ovulated in each strain were approximately 3 months apart, while gonadotrophin peaks, which were only detected about the time of ovulation, were 4 months apart. This phase shifting between the strains is discussed in terms of the environmental control of the reproductive cycle.

Animals↗
PubMed1990

Seasonal changes in gonadal steroids of a monogamous versus a polyandrous shorebird.

We examined the relationship between circulating levels of gonadal steroids (testosterone, progesterone, and estradiol) and breeding behavior in semipalmated sandpipers (Calidris pusilla) and red-necked phalaropes (Phalaropus lobatus) breeding sympatrically at La Pérouse Bay, 40 km east of Churchill, Manitoba. Semipalmated sandpipers are territorial and monogamous. Both parents incubate equally. Red-necked phalaropes are nonterritorial and polyandrous. Only male phalaropes care for eggs and young. Gonadal steroid hormone profiles were not reversed in the sex-role-reversed species. There was little difference in testosterone profiles between males of the territorial and nonterritorial species.

Animals↗
PubMed1989

Leanness, peptide hormones and premenopausal breast cancer.

Environmental factors promote the development of and decrease survival from Breast Cancer. Prospective morphological and hormonal studies indicate biological markers for this disease are evident in premenopausal women. The majority of premenopausal patients are non-obese (Body Mass Index, BMI less than 25). Lean women have a greater proportion of estrogen receptor negative (ER-) tumours, which may grow faster and have a higher concentration of epithelial growth factor (EGF). We have reported that lean, BMI less than 23, versus obese, BMI greater than 28, women have a different gut-pancreatic peptide hormone response to meals and that differences in these peptide hormones occur between healthy and age weight matched premenopausal patients. We hypothesize that the diet peptide hormone control of food intake in lean women is associated with the development of mammary dysplasia, change in growth factor profile and steroid hormone metabolism.

Breast Neoplasms↗
PubMed1994

The structure, organization and differential expression of the gene encoding rat heme oxygenase-2.

Overlapping phage lambda clones were utilized to determine the complete nucleotide (nt) sequence of the rat gene encoding HO-2, the major heme oxygenase isozyme in the brain. This isozyme is the constitutive cognate of HSP32 (HO-1). The 12,563-bp gene consists of five exons and four introns, the first two exons are separated by a large intron of 8429 nt. The minus strand of intron 1 contains a nested sequence of 1046 nt with 87% identity to the cDNAs encoding the mouse and human non-histone chromosomal protein, HMG-17. In addition to the coding region, the similarity includes 40 bp upstream from the putative start codon and 800 bp of 3' untranslated sequence. The HO-2 gene lacks a conventional TATA box, but a TATA-like sequence (TAACTA) is found 26 nt upstream from the major transcription start point (tsp), as determined by primer extension. Upstream of the tsp, only a glucocorticoid-response element is found. The structure of the regulatory region is consistent with the previously demonstrated refractory nature of this isozyme to common inducers of gene expression and its apparent response to developmental changes in the adrenal steroid hormone profile. HO-2 is encoded by two transcripts (approx. 1.3 and approx. 1.9 kb), the larger of which is translated less efficiently than the smaller. Presently, we show that the transcripts are the products of a single gene and differ in the use of the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cytochrome P-450 mediated metabolism of progesterone by adrenal microsomes of PCB-treated and untreated barn owl (Tyto alba) and marsh turtle (Mauremys caspica) in comparison with the guinea-pig.

1. Significant differences between species were observed in the profile of steroids produced from progesterone by adrenal microsomes as well as in the effects elicited by Aroclor 1254 on cytochrome P-450-mediated activities. 2. In the guinea-pig, the major metabolites were products of the corticosteroid pathway but products of the androgenic pathway were also detected; in the barn owl products of both pathways were also formed while in the marsh turtle only products of the corticosteroid pathway were detected. 3. The effect of Aroclor 1254 on P-450C21 activity in the turtle and barn owl was inductive in contrast to the inhibitory effect observed in the guinea-pig.

17-alpha-Hydroxyprogesterone↗