Norethisterone is bioconverted to oestrogenic compounds that activate both the oestrogen receptor alpha and oestrogen receptor beta in vitro. | LitMetric
In the present study, we used [3H]norethisterone to explore the bioconversion of this compound to A-ring reduced metabolites in African Green Monkey Kidney CV-1 cells and breast cancer T-47D cells. Additionally, we analyzed the capability of each norethisterone tetrahydro-reduced compound to bind the human oestrogen receptors alpha and beta and transactivate an oestrogen-sensitive reporter gene. The results showed that norethisterone is mainly metabolized to 3 alpha,5 alpha-norethisterone (>85% of total [3H]norethisterone added) by CV-1 and T-47D cells, and that both A-ring tetrahydro-reduced metabolites exhibit different capabilities to displace [3H]17beta-oestradiol from the oestrogen receptor alpha and beta, being 3 alpha,5 alpha-norethisterone the weakest competitor. We also found that 3 alpha,5 alpha-norethisterone and 3beta,5 alpha-norethisterone activate both oestrogen receptors at nanomolar concentrations and that the transactivation induced by the oestrogen receptor alpha was generally higher (1.7- to 4.0-fold) than that provoked by the beta receptor isoform. In oestrogen receptor alpha-transfected CV-1 and T-47 D cells, the oestrogenic-like potency of the 3beta,5 alpha-tetrahydro-reduced form was similar to that exhibited by 17beta-oestradiol and 2.5- to 4.0-fold higher than that shown by the 3 alpha,5 alpha-reduced compound; conversely, in the oestrogen receptor beta system the potency of the natural ligand was higher than that presented by the 3beta,5 alpha-tetrahydro-reduced metabolite. In CV-1 cells expressing the oestrogen receptor beta, the transactivation potency of 3beta,5 alpha-norethisterone was approximately 2-fold higher than that exhibited by its 3 alpha,5 alpha-tetrahydro-reduced isomer, whereas in T-47D cells the potency of the 3 alpha,5 alpha-tetrahydro-reduced compound was slightly higher than that shown by the 3beta,5 alpha A-ring reduced norethisterone metabolite. These results demonstrate that CV-1 and T-47D cells possess the enzymatic machinery to bioconvert norethisterone into the 5 alpha-reduced, 3 alpha-hydroxylated form and that neither 3 alpha,5 alpha- or 3beta,5 alpha-norethisterone exhibit preference or selectivity towards a particular oestrogen receptor isoform to induce a particular oestrogenic effect in these cell lines.
Progesterone receptor is one of the markers used in antibody-based immunohistochemistry for the diagnostics of breast cancer. The shortcomings of antibodies raise the need to focus on alternative molecular recognition. Aptamers are chosen due to their many advantages as compared to antibodies.
Department of Biological Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.
Background: Benign prostatic hyperplasia (BPH) is a disease linked to the hormonal imbalance that occurs during aging and over the last decades, complementary and alternative medicines have come on the scene as a treatment option for BPH, such as herbal medicines. Coconut oil has been shown to be capable of interfering in testosterone-induced BPH. However, until now there is no study of the effect of coconut oil during aging.
Major depressive disorder (MDD) is one of the most common diseases affecting millions of people worldwide. The use of existing antidepressants in many cases does not allow achieving stable remission, probably due to insufficient understanding of pathological mechanisms. This indicates the need for the development of more effective drugs based on in-depth understanding of MDD's pathophysiology.
Invasive lobular breast cancer (ILBC) is a common cause of breast cancer. Prognosis is dependent on many factors such as metastasis location and hormone receptor positivity. A 59-year-old postmenopausal African-American female who was referred to our clinic in May of 2022 presented with a suspicious small bowel lesion seen on surveillance imaging.
Introduction: Breast cancer liver metastasis presents a significant challenge in clinical oncology, with limited treatment options and poor prognosis. This case series study explores the extended survival achieved in breast cancer patients with liver metastases through a combination of surgical and medical interventions.
Case Presentation: We present three cases of Javanese female patients with breast cancer (51 years old, 42 years old, and 55 years old) with liver metastases who underwent hepatic resection followed by systemic therapy.
