Reproductive Steroids Flashcards
What do glucocorticoids do?
increase protein turnover & gluconeogenesis; anti-inflammatory
What do androgens do?
maintain functional activity of male reproductivesystem (spermatogenesis, accessory sex organs); anabolic(muscle) and sexual behavioural actions
What do Mineralocorticoids do?
control sodium and potassium balance in the body
What do progestagens do?
Maintain the pregnancy
What do oestrogens do?
maintain functional activity of female reproductive system (menstrual cycle and labour); also actions on cardiovascular system and bone
What tissues do steriod have an affect on?
Many - e.g. brain and nervous systen, liver, kidney, breast, skin and hair etc.
Can steroids affect cancers?
Yes
Why are steroids complex?
Multiple enzyme pathways which can be affected by the availability of substrates. There is different forms, active and inactive triggered by multiple signalling pathways (endocrine and local) with different orgna, tissue and cell interactions that can either be genomic or non genomic. There is also different receptor types with multiple pathways and promotor/receptors. Also the bioavailability of the steroids for its receptor - actions of binding proteins.
How is the human menstrual cycle controlled by steriods?
Folliculogenesis involves high eostrogen and low progesterone until just after ovulation when both are low. It then enters the embryogenesis stage and progesterone increases immensely whilst oestrogen increases once more but not as high.
What does oestrogen do to the endometrium?
Causing endometrium to proliferate
What happens after ovulation?
The empty follicle turns into the corpus luteum which secretes progesterone making the endothelium a secretionary endothelium so it can support the possibly fertilised egg.
How does the theca cell help create oestrogen from the granulosa cell?
It secretes androsteroine which works in the granulosa cell to make oestrogen
What does fertility rely upon?
Co-ordinated interactions between Hypothalamic-pituitary-ovarian axis, ovary and uterus (the targets).
What is the combined contraceptive pill?
Combination of oestrogen and progesterone which inhibits FSH and LH release preventing follicular development, egg maturation and ovulation.
What are less well defined results of the combined pill?
Unreceptive endometrium
Cervical mucus is hostile to sperm
Egg transport to fallopian tube
What are side affect of the combined pill?
Nausea, vomiting, gain of weight, loss of or increase in libido, peripheral thrombosis and prevents lactation rate.
What is the failure rate of the combined pill?
2 - 8%
What are different formulations of synthetic progesterone?
Microgynon
Logynon
Marvelon
Femodene
Patch (new one each week)
Who would use the progesterone only pill?
Older women, smokers, history of venous thrombosis, hypertension or diabetes.
What are the different forms of delivery for the progestogen only pill?
Daily pill, implant, IUDs
What are the actions of the progestogen only pill?
Makes endometrium less receptive, cervical mucus thicker and hostile to sperm. It may affect follicle development.
What are the issues/ side affects of the progestogen only contraceptive?
Menstrual irregularities
Is the timing more important in the combined or the progestogen-only contraceptive?
Progestogen
How effective is the progestogen pill?
90 - 95%
Is it better to have an emergency contraception (progesterone only contraception) earlier?
Yes and if you are sick within 2 hours you need to take it again
What is progesterone essential in?
Maintaining pregnancy
What happens in sheep fetus’s to encourage delivery?
The sheep fetus secretes cortisol from its growing adrenal gland which acts as a trigger for birth. When the cortisol level is high enough this means the sheep and therefore adrenal gland is big enough to live.
What does fetal cortisol levels stimulate?
17alpha-hydroxylase and aromatase expression in the placenta
What happens in humans - what secretes progesterone?
placental trophoblast cells
In humans is there co-operation between fetal adrenal and placenta and whats different between sheep and human placenta?
Yes but there is no 17 alpha hydroxylase in placenta unlike in sheep
Is oestradiol synthesised in cholesterol?
Yes -
Steroidogenesis in the rodent testis - what cell secretes dihydrogenase?
Leydig cells
What is the differences between P450’s and steroid dehydrogenase?
Different activities, different substrate specificities/preferences
Differential expression in cells and tissue
Species differences in human/animal model and different expression and synthetic/metabolic pathways
How does endocrine signalling work?
A signal/ hormones from one cell travels through the blood to another
How does autocrine signalling work?
A signal from one type of cell works on a neighbouring cell if it is the same type of cell e.g. two skin cells
How does paracrine signalling work?
A signal goes from one cell to a neighbouring cell that does not need to be the same type of cell e.g. skin cell to hair cell.
How does intracrine signalling work?
A signal is produced in a cell and works on a receptor within the cell itself.
What does genomic signalling involve?
Cognate steroid receptors which are ligand activated and translocate the the nucleus to act in a dimeric state.
What does non-genomic steroid signalling involve?
Some cognate receptors but trafficked to plasma membrane and may have novel GPCRs. They are typically involved in distinct signalling pathways to nuclear action ones.
What is quicker genomic or non-genomic steroid signalling?
Non-genomic takes seconds whereas genomic is slow because it involves transcription.
What is an ERE?
Eostrogen response element
How many oestrogen receptors is there and what are these called?
2 - alpha and beta
How many receptors does progesterone have and does this involve alternative gene splicing?
1 and yes (PRa and PRb)
Do oestrogen receptors need to make a dimer to work on the ERE?
Yes
Is there distinct responses to steroids?
Yes as some times they don’t need receptors to do things.
