ABSTRACT
Thyroid hormone receptor α1 (TRα1) undergoes nucleocytoplasmic shuttling and mediates gene expression in response to thyroid hormone (T3). In Resistance to Thyroid Hormone Syndrome α (RTHα), certain TRα1 mutants have higher affinity for nuclear corepressor 1 (NCoR1) and may form stable complexes that are not released in the presence of T3. Here, we examined whether NCoR1 modulates intranuclear mobility and nuclear retention of TRα1 or RTHα-associated mutants in transfected human cells, as a way of analyzing critical structural components of TRα1 and to further explore the correlation between mutations in TRα1 and aberrant intracellular trafficking. We found no significant difference in intranuclear mobility, as measured by fluorescence recovery after photobleaching, between TRα1 and select RTHα mutants, irrespective of NCoR1 expression. Nuclear-to-cytoplasmic fluorescence ratios of RTHα mutants, however, varied from TRα1 when NCoR1 was overexpressed, with a significant increase in nuclear retention for A263V and a significant decrease for A263S and R384H. In NCoR1-knockout cells, nuclear retention of A263S, A263V, P389R, A382P, C392X, and F397fs406X was significantly decreased compared to control (wild-type) cells. Luciferase reporter gene transcription mediated by TRα1 was significantly repressed by both NCoR1 overexpression and NCoR1 knockout. Most RTHα mutants showed minimal induction regardless of NCoR1 levels, but T3-mediated transcriptional activity was decreased for R384C and F397fs406X when NCoR1 was overexpressed, and also decreased for N359Y in NCoR1-knockout cells. Our results suggest a complex interaction between NCoR1 and RTHα mutants characterized by aberrant intracellular localization patterns and transcriptional activity that potentially arise from variable repressor complex stability, and may provide insight into RTHα pathogenesis on a molecular and cellular level.
ABSTRACT
OBJECTIVES: This study describes hormonal contraception services provided by pharmacists and characterizes patient populations utilizing the service at one supermarket-based pharmacy chain in California and Oregon. STUDY DESIGN: This is a descriptive study of 391 pharmacies in California and Oregon within a supermarket-based pharmacy chain providing hormonal contraception services and the patients who utilized those services in a 6.5-month period between August 2016 and February 2017. Data were extracted from pharmacy prescription records and available visit documentation forms to describe services provided and patient characteristics. RESULTS: During the study period, 381 trained pharmacists from the pharmacy chain provided hormonal contraception services in 391 pharmacy locations in Oregon and California. A total of 2117 visits were completed and 1970 hormonal contraception prescriptions were issued and dispensed during the study period. Researchers were able to access documentation for 676 visits (32%). Patients from various age groups (range 13-55â¯years old) and geographical locations (22 states total) utilized the service. Most had health insurance (74%), had seen a primary care provider in the past year (89%) and were previous hormonal contraception users (91%). Contraceptive methods prescribed include pill (n=1886, 95.7%), patch (n=31, 1.6%), vaginal ring (n=51, 2.6%) and injectable (n=2, 0.1%). CONCLUSION: Following scope of practice expansion, pharmacists in a community-based pharmacy setting are serving as an access point for women to obtain hormonal contraception services and supplies. IMPLICATIONS: This study provides an initial look at California's and Oregon's expansion of hormonal contraception prescribing authority to pharmacists. The service was available across all pharmacy locations of a supermarket-based chain in California and select locations in Oregon and utilized by diverse populations of patients. Pharmacists effectively provided hormonal contraception services and supplies to most patients seeking hormonal contraception.