Hormone regulated cancer

• Nuclear Hormone Receptors are a super family of transcription factors and transcriptional complexes recruited to the area determine the transcription start site.
• Nuclear Hormone Receptors bind to specific DNA segments throughout the genome, leading to changes in chromatin by recruiting chromatin remodelers to the area.
• The conformational change and the binding of Nuclear Hormone Receptors lead to the recruitment of the transcription machinary to the area.
• There are 7 classes of the superfamily of nuclear hormone receptors, focusing on class 3 which includes the glucocorticoid, androgen and estrogen receptors.
• Nuclear Hormone Receptors are critical for the homeostasis in our body, hence why they are very tightly regulated.
• Disruption in the system of Nuclear Hormone Receptors causes many pathologies, one of them being cancers and metabolic disorders like diabetes.
• The top 5 ligands of Nuclear Hormone Receptors have very similar structures as they are steroid hormones.
• Retinoic acids and vitamin D3 can also present themselves as ligands for nuclear receptors.
• Increase in growth can lead to an increase in survival, increase in PSA (prostate specific antigen), and possible progressive growth of prostate cancer.
• It is possible to target components that are involved in prostate cancer growth.
• Dimerization leads to DNA binding, which in turn leads to transcriptional activation or regression.
• Inhibiting the step involved in testosterone production, 5 a - reductase, which is responsible for testosterone conversion to DHT, can help block binding of testosterone to its respective receptor.
• Prostate cancer biomarkers (PSA) are screened in the bloodstream to see if a patient may potentially have prostate cancer.
• Hormonal therapy in prostate cancer involves the use of drugs that can inhibit prostate cancer proliferation at various stages.
• Eliminating testicular production of testosterone, as 90% of testosterone is produced here, can help suppress hormones that lead to stimulation of the testes.
• The molecular basis of androgen receptor function involves the binding of testosterone to the androgen receptor, causing a conformational change that leads to dimerization.
• The function of Nuclear Hormone Receptors is transcription and HREs.
• Under stress, our body receives a signal which is noticed by the hypothalamus, stimulating the release of CRF (corticotropin realising factor).
• The hypothalamus then stimulates the pituitary glands which releases ACTH (adrenocorticotropic hormone).
• ACTH reaches the adrenal glands as a result cortisol is released.
• Cortisol is then able to bind to receptors on target cells.
• The hypothalamus receives stimulation and upon stimulation hypothalamus is then able to release GnRH (gonadotropin releasing hormone).
• GnRH reaches the anterior pituitary which starts to release stimulating hormones LH (leuteinizing hormone) and FSH (follicle stimulating hormone).
• LH and FSH then stimulate the target tissues, the corpus luteum in the ovaries to release progesterone and the follicle in the ovaries to release estrogen.
• Raloxifen is another treatment option for breast cancer, with one tablet taken daily for 5 years.
• Once stopped taking Tamoxifen, the benefits will last for 11 years.
• 16/1000 women will get a blood clot while using Raloxifen.
• Once stopped taking Raloxifen, the benefits will last for 2 years.
• While taking Raloxifen, 43/1000 women will develop cancer.
• While taking Tamoxifen, 35/1000 women will develop cancer.
• Raloxifen does not increase the risk of endometrial cancer.
• 20/1000 women will get a blood clot while using Tamoxifen.
• Prostate cancer is managed by hormone secretion involving the Hypothalamus, Pituitary glands, Testes.
• The testosterone binds to the DNA, which can lead to cell proliferation.
• Aromatase is the enzyme that converts androgens (testosterone and androstenedione) to estrogens (estradiol and estrone).
• SERMs are all synthetic.
• Aromatase is a microsomal cytochrome P450 in which the haem protein binds the androgenic substrate and catalyzes a series of reactions that lead to the formation of the phenolic A - ring.
• Different aromatase inhibitors that are available include Faslodex (fulvestrant), Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole).
• It is possible to produce some testosterone from the adrenal glands, with 90% coming from the testes and 10% from the adrenal glands.
• Aromatase Inhibitors are used in postmenopausal women or obese, high plasma estrogen levels are associated with an increased risk of breast cancer.