Lecture 17 Flashcards
What are some examples of molecules which act via nuclear receptors?
Nuclear receptors are activated by a range of hormones e.g testosterone, oestrogen and cortisol, they represent roughly 10-15% of drugs in clinical use, particularly for cancer and inflammation.
How do nuclear receptors work?
The receptor is found in the cytosol and when unactivated is simply floating around, when the agonist binds it forms a drug/receptor complex, two of these complexes join together to forma dimer, this then binds to a specific part of the DNA called the hormone response element and initiates the transcription of certain genes (leading to new proteins).
Summarise nuclear receptors.
They are ligand activated transcription factors located in the cytosol and nucleus, the effector is gene transcription, coupling is via hormone response element, the response time is hours and a good exaample is the oestrogen receptor.
What are the main points for testosterone?
Testosterone is a hormone which activates the androgen receptor (nuclear receptor), clinical use is done via modifies testosterone compoundds for replacement therapy. However it has some adverse drug reactions such as infertility, increased risk of heart attacks and strokes. Non clinically it is often used to increase muscle mass.
How does testosterone cause infertility?
The anterior pituitary releases luteinizing hormone and follicle stimulating hormone in response to gonadotropin releasing hormone from the hypothalamus. The testes secrete testosterone in response to LH and FSH, this inhibits action of the anterior pituitary and the hypothalamus secretion. If we flood the system with testosterone (not the testes) then the testosterone production and hence the production of sperm (which requires testosterone in the testes).
Why isn’t the male contraceptive out yet?
The male contraception isn’t common because the female option is relatively safe and effective (increases risk of deep vein thrombosis), the safety standards are much stricter now than when the female pill came out, this makes it harder to bring out the male pill, it is harder to stop and start the sperm production (3 months forwards or back), there is also no current oral option, big pharma has also withdrawn support.
