scholarly journals Steroid inhibition of calcitriol-induced prolactin production in GH4C1 cells. Specificity and sensitivity

1987 ◽  
Vol 241 (2) ◽  
pp. 397-401 ◽  
Author(s):  
J D Wark ◽  
V Gurtler
Keyword(s):  
Pituitary Tumour ◽  
Dependent Manner ◽  
Hormone Production ◽  
Concentration Dependent Manner ◽  
Dihydroxyvitamin D3 ◽  
Specificity And Sensitivity ◽  
Rat Pituitary ◽  
Increased Sensitivity ◽  
Ic50 Concentration ◽  
Glucocorticoid Effect

The induction of prolactin (PRL)-gene expression by calcitriol (1,25-dihydroxyvitamin D3, 1,25-dihydroxycholecalciferol) in clonal rat pituitary tumour (GH4C1) cells was selectively inhibited by cortisol [IC50 (concentration causing 50% inhibition) = 3.2-4.1 nM]. The steroid specificity of this effect was investigated and various steroids were found to inhibit calcitriol-stimulated PRL production with the following relative potencies: cortisol, 1; dexamethasone, 8; 11-deoxycortisol, 0.5; corticosterone, 0.4; aldosterone, 0.07; testosterone and oestradiol, less than 0.003. The steroid antagonist RU 38486 did not affect basal or calcitriol-stimulated PRL production, but antagonized the effect of 10 nM-cortisol in a concentration-dependent manner. Neither progesterone nor 11-deoxycortisol antagonized the effect of 10 nM-cortisol. Calcitriol-induced PRL production was 14 times more sensitive to dexamethasone inhibition than was non-stimulated PRL production. Growth-hormone production was stimulated by dexamethasone, in the presence or absence of calcitriol, with a concentration-dependence similar to that of dexamethasone inhibition of basal PRL production. These data indicate that steroid inhibition of calcitriol-stimulated PRL production is a specific glucocorticoid effect. The sensitivity of calcitriol-stimulated PRL production to dexamethasone was 14-26-fold greater than that of other measured responses in the same cells. Two of the possible explanations for this selectively increased sensitivity to glucocorticoids are: amplification of the glucocorticoid effect via an induced mediator; and the presence of very-high-affinity glucocorticoid-receptor-binding sites on DNA.

Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells

1985 ◽  
Vol 110 (2) ◽  
pp. 200-206 ◽  
Author(s):  
P. W. Johansen ◽  
E. Haug ◽  
K. M. Gautvik
Keyword(s):  
Cell Line ◽  
Hepatoma Cell ◽  
Cellular Growth ◽  
Maximum Effect ◽  
Epithelial Cell Line ◽  
Hepatoma Cell Line ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Hormone Production ◽  
Rat Pituitary

Abstract. Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 × 10−5 mol/l), a dopamine (DA) agonist, induced a rapid reduction in Prl and GH secretion with maximum effect (approximately 60%) after 15 min of treatment. Bromocriptine also inhibited Prl and GH production in a time- and dose-dependent manner with ED50 at 4 × 10−6 mol/l and 7 × 10−6 mol/l, respectively. Maximum effect was obtained at 5 × 10−5 mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by ∼ 70 and ∼ 50%, respectively. After 9 days of treatment both Prl and GH production was reduced by more than 95%. Bromocriptine also reduced cellular growth rate. The ED50 was ∼ 1 × 10−5 mol/l and the maximum effect (> 50%) was observed at 5 × 10−5 mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The anti-proliferative effect of bromocriptine was also observed using a rat hepatoma cell line (MH1C1) and a human epithelial cell line (HE), suggesting a non-receptor mediated growth inhibition at high concentrations of the drug. In conclusion, the inhibitory effect of bromocriptine on secretion and production of both Prl and GH in GH3 cells occurs at a lower concentration than its effect on cell proliferation. The pharmacological effects of bromocriptine in vivo on Prl and GH producing adenomas may be explained by an action directly at the pituitary level.

scholarly journals The γ-aminobutyrate/benzodiazepine receptor from pig brain. Enhancement of γ-aminobutyrate-receptor binding by the anaesthetic propanidid

1986 ◽  
Vol 233 (1) ◽  
pp. 259-264 ◽  
Author(s):  
E F Kirkness ◽  
A J Turner
Keyword(s):  
Gaba Receptor ◽  
Benzodiazepine Receptor ◽  
Functional Characteristic ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gaba Receptor Complex ◽  
Triton X ◽  
Muscimol Binding ◽  
Ic50 Concentration ◽  
Stimulation Of

The binding of [3H]muscimol, a gamma-aminobutyrate (GABA) receptor agonist, to a membrane preparation from pig cerebral cortex was enhanced by the anaesthetic propanidid in a concentration-dependent manner. At 0 degrees C, binding was stimulated to 220% of control values, with 50% stimulation at 60 microM-propanidid. At 37 degrees C, propanidid caused a more powerful stimulation of [3H]muscimol binding (340% of control values). Propanidid (1 mM) exerted little effect on the affinity of muscimol binding (KD approx. 10 nM), but increased the apparent number of high-affinity binding sites in the membrane by 2-fold. Enhancement of [3H]muscimol binding was observed only in the presence of Cl- ions, half-maximal activation being achieved at approx. 40 mM-Cl-. Picrotoxinin inhibited the stimulation of [3H]muscimol binding by propanidid with an IC50 (concentration causing 50% inhibition) value of approx. 25 microM. The enhancement of [3H]muscimol binding by propanidid was not additive with the enhancement produced by secobarbital. Phenobarbital inhibited the effect of propanidid and secobarbital. The GABA receptor was solubilized with Triton X-100 or with Chaps [3-[(3-cholamidopropyl)dimethylammonio]propanesulphonate]. Propanidid and secobarbital did not stimulate the binding of [3H]muscimol after solubilization with Triton X-100. However, the receptor could be solubilized by 5 mM-Chaps with retention of the stimulatory effects of propanidid and secobarbital. Unlike barbiturates, propanidid did not stimulate the binding of [3H]flunitrazepam to membranes. It is suggested that the ability to modulate the [3H]muscimol site of the GABA-receptor complex may be a common and perhaps functional characteristic of general anaesthetics.

Effects of glucocorticosteroids on prolactin and growth hormone production and characterization of the intracellular hormone receptors in rat pituitary tumour cells

1980 ◽  
Vol 95 (3) ◽  
pp. 319-327 ◽  
Author(s):  
Oddvar Naess ◽  
Egil Haug ◽  
Kaare Gautvik
Keyword(s):  
Growth Hormone ◽  
Hormone Receptors ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Scatchard Analysis ◽  
Hormone Production ◽  
Single Class ◽  
High Affinity ◽  
Rat Pituitary

Abstract. The effect of corticosterone and dexamethasone on the production of growth hormone and prolactin was studied in rat pituitary tumour cells (GH3-cells) in culture. Corticosterone and dexamethasone caused a dose-dependent stimulation of growth hormone synthesis, and the highest concentration (10−6 mol/l) increased growth hormone levels to 250% of controls. This concentration, however, decreased prolactin synthesis to 25% of the control values. The cytosol fractions from monolayer cultures as well as from tumours of GH3-cells were found to possess receptor molecules for glucocorticoid hormones, having a sedimentation constant close to 8 S in a salt-free buffer and 4 S in the presence of 0.5 mol/l KCL. Isoelectric point of the receptor was 5.8. Scatchard analysis showed one single class of binding sites with high affinity (Kd 2.1 ± 0.4 (sd × 10−9 mol/l). Studies on the steroid specificity revealed that dexamethasone had the highest affinity for the receptor. Corticosterone, cortisol and progesterone had also high affinity, whereas testosterone and oestradiol-17β had no significant affinity for the receptors. After in vivo administration of [3H]dexamethasone to GH3 tumour-bearing rats, radioactivity could be extracted from purified nuclei bound to 4 S macromolecules. The presence of receptors for glucocorticosteroid hormones in the GH3-cells, suggests that these hormones may alter growth hormone and prolactin production at the anterior pituitary level.

Acetylcholine increases intracellular Ca2+ in the rat pituitary folliculostellate cells in primary culture

2001 ◽  
Vol 280 (4) ◽  
pp. E608-E615 ◽  
Author(s):  
Yusaku Nakajima ◽  
Maki Uchiyama ◽  
Yasumasa Shirai ◽  
Yasuo Sakuma ◽  
Masakatsu Kato
Keyword(s):  
Phospholipase C ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Dependent Manner ◽  
Bioactive Substances ◽  
Concentration Dependent Manner ◽  
Cellular Processes ◽  
Folliculostellate Cells ◽  
Rat Pituitary ◽  
Male Wistar Rats

Pituitary folliculostellate cells (FSCs) are thought to partially inhibit pituitary hormone secretion through a paracrine mechanism. In this process, one of the important questions is what factors regulate the function of FSCs. Because ACh is synthesized in and possibly released from the corticotrophs and lactotrophs, we examined whether FSCs respond to ACh by the method of Ca2+ imaging in primary cultured FSCs from male Wistar rats. ACh (30 nM-3 μM) increased intracellular calcium concentration ([Ca2+]i) of FSCs in a concentration-dependent manner, with an initial rapid rise followed by a relatively sustained increase. The complete block of the response by atropine and pirenzepine suggests involvement of muscarinic receptors. Depletion of the stored Ca2+ by thapsigargin blocked the response completely. Blockers of phospholipase C, U-73122 and neomycin, suppressed significantly the rise of [Ca2+]i. These results suggest that ACh increases [Ca2+]i in FSCs by activating phospholipase C, presumably through activation of M1receptors. The rise in [Ca2+]i could trigger a variety of Ca2+-dependent cellular processes, including the synthesis and release of bioactive substances, which in turn act on endocrine cells.

Low-Mg2+ treatment increases sensitivity of voltage-gated Na+ channels to Ca2+/calmodulin-mediated modulation in cultured hippocampal neurons

2015 ◽  
Vol 308 (8) ◽  
pp. C594-C605 ◽  
Author(s):  
Feng Guo ◽  
Pei-Dong Zhou ◽  
Qing-Hua Gao ◽  
Jian Gong ◽  
Rui Feng ◽  
...  
Keyword(s):  
Binding Sites ◽  
Hippocampal Neurons ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Functional Roles ◽  
Voltage Gated ◽  
Increased Sensitivity ◽  
Cam Regulation

Culture of hippocampal neurons in low-Mg2+ medium (low-Mg2+ neurons) results in induction of continuous seizure activity. However, the underlying mechanism of the contribution of low Mg2+ to hyperexcitability of neurons has not been clarified. Our data, obtained using the patch-clamp technique, show that voltage-gated Na+ channel (VGSC) activity, which is associated with a persistent, noninactivating Na+ current ( INa,P), was modulated by calmodulin (CaM) in a concentration-dependent manner in normal and low-Mg2+ neurons, but the channel activity was more sensitive to Ca2+/CaM regulation in low-Mg2+ than normal neurons. The increased sensitivity of VGSCs in low-Mg2+ neurons was partially retained when CaM12 and CaM34, CaM mutants with disabled binding sites in the N or C lobe, were used but was diminished when CaM1234, a CaM mutant in which all four Ca2+ sites are disabled, was used, indicating that functional Ca2+-binding sites from either lobe of CaM are required for modulation of VGSCs in low-Mg2+ neurons. Furthermore, the number of neurons exhibiting colocalization of CaM with the VGSC subtypes NaV1.1, NaV1.2, and NaV1.3 was significantly higher in low- Mg2+ than normal neurons, as shown by immunofluorescence. Our main finding is that low-Mg2+ treatment increases sensitivity of VGSCs to Ca2+/CaM-mediated regulation. Our data reveal that CaM, as a core regulating factor, connects the functional roles of the three main intracellular ions, Na+, Ca2+, and Mg2+, by modulating VGSCs and provides a possible explanation for the seizure discharge observed in low-Mg2+ neurons.

Normal and abnormal sexual differentiation

2020 ◽  
pp. 2435-2448
Author(s):  
S. Faisal Ahmed ◽  
Angela K. Lucas-Herald
Keyword(s):  
Sexual Differentiation ◽  
Fetal Development ◽  
Sex Chromosome ◽  
Disorders Of Sex Development ◽  
Androgen Insensitivity Syndrome ◽  
Dependent Manner ◽  
Hormone Production ◽  
Concentration Dependent Manner ◽  
Sex Development ◽  
Partial Androgen Insensitivity Syndrome

Human sex development follows an orderly sequence of embryological events coordinated by a cascade of gene expression and hormone production in a time- and concentration-dependent manner. Underpinning the entire process of fetal sex development is the simple mantra: sex chromosomes (XX or XY) dictate the gonadotype (ovary or testis), which then dictates the somatotype (female or male phenotype). The constitutive sex in fetal development is female. Disorders of sex development (DSD) can be classified into three broad categories based on the knowledge of the karyotype: sex chromosome abnormality (e.g. X/XY, mixed gonadal dysgenesis); XX DSD (e.g. congenital adrenal hyperplasia); XY DSD (e.g. partial androgen insensitivity syndrome).

Normal and abnormal sexual differentiation

2010 ◽  
pp. 1963-1975 ◽  
Author(s):  
I.A. Hughes
Keyword(s):  
Gene Expression ◽  
Sex Chromosomes ◽  
Sexual Differentiation ◽  
Dependent Manner ◽  
Hormone Production ◽  
Concentration Dependent Manner ◽  
Fetal Sex ◽  
Entire Process ◽  
Sex Development ◽  
Male Phenotype

Human sex development follows an orderly sequence of embryological events coordinated by a cascade of gene expression and hormone production in a time- and concentration-dependent manner. Underpinning the entire process of fetal sex development is the simple mantra: sex chromosomes (XX or XY) dictate the gonadotype (ovary or testis), which then dictates the somatotype (female or male phenotype)....

scholarly journals Highly Sensitive and Cost-Effective Portable Sensor for Early Gastric Carcinoma Diagnosis

Sensors ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 2639
Author(s):  
Saw Lin Oo ◽  
Shishir Venkatesh ◽  
Vaithinathan Karthikeyan ◽  
Clement Manohar Arava ◽  
Spoorthy Pathikonda ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
High Specificity ◽  
Cost Effective ◽  
Electrical Current ◽  
Early Gastric Carcinoma ◽  
Rna Modification ◽  
Dependent Manner ◽  
Cancer Antigen ◽  
Concentration Dependent Manner ◽  
Specificity And Sensitivity

Facile and efficient early detection of cancer is a major challenge in healthcare. Herein we developed a novel sensor made from a polycarbonate (PC) membrane with nanopores, followed by sequence-specific Oligo RNA modification for early gastric carcinoma diagnosis. In this design, the gastric cancer antigen CA72-4 is specifically conjugated to the Oligo RNA, thereby inhibiting the electrical current through the PC membrane in a concentration-dependent manner. The device can determine the concentration of cancer antigen CA72-4 in the range from 4 to 14 U/mL, possessing a sensitivity of 7.029 µAU−1mLcm−2 with a linear regression (R2) of 0.965 and a lower detection limit of 4 U/mL. This device has integrated advantages including high specificity and sensitivity and being simple, portable, and cost effective, which collectively enables a giant leap for cancer screening technologies towards clinical use. This is the first report to use RNA aptamers to detect CA72-4 for gastric carcinoma diagnosis.

scholarly journals A peptide mimetic of the mycobacterial mannosylated lipoarabinomannan: characterization and potential applications

2007 ◽  
Vol 56 (5) ◽  
pp. 579-586 ◽  
Author(s):  
Ayelet Barenholz ◽  
Avi-Hai Hovav ◽  
Yolanta Fishman ◽  
Galia Rahav ◽  
Jonathan M. Gershoni ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phage Display ◽  
Peptide Libraries ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Keyhole Limpet Haemocyanin ◽  
Peptide Epitope ◽  
Specificity And Sensitivity ◽  
Potential Applications ◽  
Good Substitute

Mannosylated lipoarabinomannan (ManLAM), a complex lipoglycan, is a major component of Mycobacterium tuberculosis, the agent of tuberculosis (TB), and is an antigen used for serological diagnosis of TB. Screening random phage-display peptide libraries with anti-ManLAM mAb CS40 for peptide epitope mimics (mimotopes) led to the isolation of a panel of peptides. One of these peptides (B11) was characterized as a ManLAM mimotope: it bound the anti-ManLAM CS40 mAb and competed with ManLAM for antibody binding. Mice immunized with keyhole limpet haemocyanin-conjugated B11 peptide in a proper adjuvant developed antibodies that recognized ManLAM. Competition experiments demonstrated that the B11 peptide inhibited binding of mAb CS40 to ManLAM in a concentration-dependent manner. The data indicated that the affinity of CS40 mAb to B11 (K D 1.33×10−8) is higher than its affinity to ManLAM (K D 3.00×10−7). The sera of TB patients, as well as the sera of mice experimentally infected with M. tuberculosis, contained significant levels of antibodies that recognized both the B11 peptide and ManLAM. The specificity and sensitivity of the ELISA B11-based test were similar to those of the ELISA ManLAM-based test, indicating that the B11 antigen could be a good substitute for ManLAM serology for the diagnosis of TB.

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