Prolactin Interaction with its Receptors and the Relationship to the Subsequent Regulation of Metabolic Processes
James A. Rillema in Actions of Prolactin on Molecular Processes, 1987
Down regulation in mammary tumor cells requires energy, but not the integrity of cytoskeletal elements, which is also true for normal mammary tissue.118 In addition, NH4Cl, which prevents hormone degradation in both normal and neoplastic tissue, does not inhibit down regulation in tumor cells. This indicates that hormone degradation is not essential for down regulation, and it does not appear to be necessary for biologic responsiveness.115,121 It has been suggested that NH4C1 prevents prolactin receptor down regulation in normal mammary gland.124 Initially, this might appear to be a potentially important difference in normal vs. neoplastic mammary cell receptor processing. This apparent difference, however, can be explained by the different methods employed. In tumor cells, down regulation was defined as a decrease in cell surface receptors.34 By contrast, in normal mammary tissue,124 receptors were quantitated in membrane preparations having both surface and internalized receptors. Thus, NH4Cl blocks hormone degradation without preventing uptake of prolactin-receptor complexes, but also inhibits degradation of internalized receptors. Preliminary experiments in our laboratory indicate that prolactin binding increases in membranes prepared from cells treated with NH4C1. Thus, NH4C1 may also prevent receptor degradation in tumor cells.
ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
Receptor sensitization is not to be confused with DOWN REGULATION, which occurs when receptors are exposed to stimulation over longer periods of time (hours rather than minutes). Down-regulation involves changes in the numbers of BINDING SITES and destruction of receptor PROTEINS, over and above the changes in second messenger activation brought about by short term sensitization. UP-REGULATION can also occur. It is typically seen when a NEURON loses its normal inputs through natural or experimental degeneration. Up-regulation is typically manifest through increased numbers of receptor binding sites. The terms SUBSENSITIVITY and SUPERSENSITIVITY are also used to describe down- and up-regulation respectively. In biological psychology, the most common demonstration of super-sensitivity is the behavioural response to DOPAMINE receptor stimulation in rats that bear a UNILATERAL dopamine-depleting LESION of the NIGROSTRIATAL DOPAMINE SYSTEM; see ROTATION for an explanation of this.
Pharmacological management of depression in older people
Stephen Curran, John P Wattis in Practical Management of Affective Disorders in Older People, 2018
For nearly 40 years, the principal theory to explain the biological basis of depression has been the monoamine hypothesis. This theory proposes that depression is due to a deficiency in one or more of three monoamines, namely noradrenaline, serotonin and dopamine in the synaptic clefts of the appropriate neurones. For example, tricyclic antidepressants (TCAs) block the neurotransmitter reuptake pump, causing neurotransmitters to accumulate in the synaptic cleft thus returning the neuron to a ‘normal state’. However, despite the fact that neurotransmitter levels return to normal fairly quickly the clinical effect is delayed as is the down-regulation of receptor sensitivity. A related theory is the monoamine receptor hypothesis. The consequence of neurotransmitter depletion is that postsynaptic receptors become up-regulated (increased in number) and the degree of up-regulation correlates with the degree of depression. In addition, down-regulation correlates with the onset of antidepressant action.10
Flow cytometry and receptor occupancy in immune-oncology
Published in Expert Opinion on Biological Therapy, 2022
Alessandra Audia, Gregory Bannish, Rachel Bunting, Chelsea Riveley
The biology of the target receptor and its role in delivering the biotherapeutic message to the cells in order to modify a mechanism otherwise altered, is of fundamental importance for design of a ROA. In association to these methods, modulation of ROA can be designed to assess modification in the biologic turnover of the receptor upon binding to the biotherapeutic. These modifications may involve up-regulation, down-regulation, internalization of the target receptor or even release of membrane-bound receptors. Modulation of ROA can be also used to assess drug interference during combo treatment (labeled biotherapeutic in combination with therapeutic B) that can be observed through change in fluorescence of the labeled biotherapeutic (Figure 2). Receptor modulation assessment can be performed by monitoring changes in total receptor relative to drug treatment dosage and time.
Silica nanoparticles on the oral delivery of insulin
Published in Expert Opinion on Drug Delivery, 2018
Xinyi Tan, Xiaolin Liu, Yan Zhang, Hongjuan Zhang, Xiaoyang Lin, Chenguang Pu, Jingxin Gou, Haibing He, Tian Yin, Yu Zhang, Xing Tang
Transcellular transport can be achieved by absorptive polarized enterocytes and epithelial microfold cells (M cells), which are mostly located at the ileum and overlaid on Peyer’s patches. Dependent on cell type, incubation time or physical properties of SNs such as size, surface area, shape and surface chemistry, endocytic uptake of naked SNs can mostly be achieved by nonspecific clathrin- or caveolin-mediated endocytosis or clathrin- and caveolin-independent endocytosis [43,80–82]. Like most nanoparticles, nonspecific absorption can be limited, and thus surface functionalization by with bioactive ligands such as CSK peptide, Fc fragment, transferrin, wheat germ agglutinin (WGA), some vitamins including folic acid, vitamin B12, and biotin can be applied to specifically target corresponding receptors or macromolecules and efficiently increase oral uptake. However, down regulation of these receptors is possible in vivo, which likely influences the long-term administration.
Bemfola® fixed dose pens potentially reduce drug wastage and associated costs of infertility treatment
Published in Human Fertility, 2018
Graham Foxon, Paul Mitchell, Nikki Turner, Anne McConnell, Helen Kendrew, Julian Jenkins
An audit was conducted in which fertility centres across the UK were asked to provide retrospective data for the previous 12 months, related to the use of Gonal-f® or Menopur® for IVF/ICSI treatment cycles. Five UK fertility clinics, representing both private and NHS funded clinics, responded providing individual cycle data on: (i) number of treatment cycles conducted in the previous 12 months; (ii) daily dose of Gonal-f® or Menopur® used per cycle; (iii) FSH formulation(s) prescribed; (iv) average number of days to first ultrasound scan; (v) dose adjustment following ultrasound scan; (vi) average length of Gonal-f® or Menopur® treatment cycles and (vii) down regulation protocol used for each cycle. The data were provided on a data input sheet developed for this study. No personal patient data, such as age, cause of infertility or partner evaluation, were collected for this analysis. All submitted cycles were analysed and there was no data censoring. Starting dose, type of FHS and dose adjustments were prescribed as per each clinic’s routine clinical practice.
Related Knowledge Centers
- Biochemistry
- Protein
- Rna
- Liver
- Neurotransmitter
- Receptor
- Regulation of Gene Expression
- Gene Product
- Cell
- Hormone