L4: Sex Steroids Flashcards
What are the classes of steroid hormones?
- glucocorticoids
- mineralcorticoids
- androgens
- progestagens
- oestrogens
What is the function of glucocorticoids?
increase protein turnover and gluconeogenesis, anti-inflammatory
What is the function of mineralcorticoids?
control sodium and potassium balance in the body
What is the function of androgens?
maintain functional activity of male reproductive system, anabolic and sexual behaviours
What is the function of progestagens?
maintenance of pregnancy
What is the function of oestrogens?
maintain functional activity of female reproductive system (menstrual cycle and labour); also actions on cardiovascular system and bone
Define the complexity of steroid hormones, six possible forms
- Multiple enzyme pathways
- They are reflected by availability of substrate, complicated because you can make steroids from cholesterol everywhere in every membrane
- There is a possibility of interaction and interconversion between active and inactive forms
- There’s multiple signalling pathways (not only genomic, but there’s also non-genomic)
i) They can act in endocrine or local effect (paracrine, autocrine)
ii) Organ, tissue and cell interactions because of receptor expression and availability
iii) Genomic and non-genomic - Multiple receptor types
i) With multiple molecular pathways
ii) With multiple promotor / repressor transcription actions - Bioavailability of the steroid for its receptor – actions of binding proteins
Which hormones control the human menstrual cycle and how?
- estrogen (follicle steroidogenesis)
- progesterone (corpus lutem steroidogenesis)
What is the length of the human mesntrual cycle?
28 days
On which day of menstrual cycle do humans ovulate?
14
What happens during ovulation? Hormone changes, uterine lining changes
- After ovulation, empty follicle turns into corpus luteum (progesterone factory), which then turns proliferative uterus into secretory uterine lining, it’s secretory so it can support fertilized oocyte
What is the receptive state of the menstrual cycle? how long is it
State of the uterine lining ready for implantation, days 20-24, 7-10 days in secretory phase
What are the principal pathways of steroidogenesis in follicular cells?
Theca cell is producing substrate that is being released to granulosa cell and then that makes the oestrogen.
Check L4, SLIDE 9 for diagramm
What are the potential targets to disrupt the fertility of the human menstrual cycle (contraception)?
Fertility relies upon co-ordinated interactions between Hypothalamic-Pituitary-Ovarian axis, ovary and uterus –> targets
- folliculogenesis
- ovulation
- embryogenesis
- estrogen
- LH, FSH
- Progesterone
- Receptive state
What is the combined contraceptive pill?
combination of an oestrogen and a progesterone analogue, taken 21 of 28 days
What is the mechanism of combined contraceptive pill?
primary mechanism - inhibits FSH and LH release, preventing:
- follicular development
- egg maturation
- ovulation
other actions:
- unreceptive endometrium
- cervical mucus is hostile to sperm
- egg transport in fallopian tube
What are the side effects of combined contraceptive pill?
- nausea and vomiting
- weight gain
- loss of, or increase in, libido
- peripheral thrombosis (risk increases with age and smoking)
- prevents lactation
What is the failure rate of combined contraceptive pill?
- ‘perfect’ use 0.3% (e.g. randomised controlled trial)
- in ‘real life’, 2-8%
What are the examples of combined contraceptive pill?
- many different formulations of synthetic progesterone (e.g. levonotgestrel) and oestrogen (e.g. ethinylestradiol)
- microgynon 30 (Schering)
- Logynon (Schering)
- Marvelon (Organon)
- Femodene (Schering)
When are progestogen-only contraceptives used?
- For older women,
- heavy smokers,
- patients with history of venous thrombosis, hypertension, diabetes mellitus
What is the available medication as progestogen-only contraceptives?
- daily progesterone as a pill (levonorgestrel)
- depot i.m. every 3 months (medroxyprogesterone acetate)
- implant (etonogestrel in implant 3 years)
- intrauterine (IUDs) (levonorgestrel release)
What are the actions of progestogen-only contraceptives?
- endometrium less receptive
- cervical mucus thicker and hostile to sperm
- may affect follicle development
What is important to know when using progestogen-only contraceptives?
- timing more important - take at the same time each day - don’t affect ovulation so protection window is shorter
What are the side effects of progestogen-only contraception?
- menstrual irregularities, although these usually resolve
- some really don’t get on well, and they get sort of prolonged light blood flow
What is emergency contraception?
- Progesterone only contraception, within 72 hours, and again 12 hours later
- more effective if taken earlier
How is fetal adrenal gland important in pregnant sheep?
- There’s then a signalling cascade of events that stimulate labour and that’s reliant on the foetus: foetus is maturing, and it is a reflection of that maturation – adrenal gland is maturing. Adrenal gland produces cortisol, which is useful for the maturation of the foetus, because it makes its lungs develop. But it’s also a timing signal for delivery of the baby
- That glucocorticoid (cortisol) from the foetal adrenal gland regulating the steroid production, so it can produce oestrogen
How is fetal adrenal gland important in pregnant sheep?
cortisol stimulates the 17alpha-hydroxylase, which allows the substrate to move from progesterone through synthetic pathway, which ends up in oestrogen production
What are the two types of steroid hormone action?
- Genomic:
i) Slow – involves transcription (>30 mins)
ii) Involves cognate steroid receptors
iii) Ligand-activated receptors translocate to nucleus (act in dimeric state) - Non-genomic:
i) Rapid
ii) May involve same cognate receptors but trafficked to plasma membrane (act in monomeric state)
iii) May be novel GPCRs
iv) Typically involve distinct signalling pathways to nuclear action ones
