L4: Sex Steroids

Question 1

What are the classes of steroid hormones?

Answer 1

• glucocorticoids
• mineralcorticoids
• androgens
• progestagens
• oestrogens

Question 2

What is the function of glucocorticoids?

Answer 2

increase protein turnover and gluconeogenesis, anti-inflammatory

Question 3

What is the function of mineralcorticoids?

Answer 3

control sodium and potassium balance in the body

Question 4

What is the function of androgens?

Answer 4

maintain functional activity of male reproductive system, anabolic and sexual behaviours

Question 5

What is the function of progestagens?

Answer 5

maintenance of pregnancy

Question 6

What is the function of oestrogens?

Answer 6

maintain functional activity of female reproductive system (menstrual cycle and labour); also actions on cardiovascular system and bone

Question 7

Define the complexity of steroid hormones, six possible forms

Answer 7

• 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

Question 8

Which hormones control the human menstrual cycle and how?

Answer 8

• estrogen (follicle steroidogenesis)
• progesterone (corpus lutem steroidogenesis)

Question 9

What is the length of the human mesntrual cycle?

Answer 9

28 days

Question 10

On which day of menstrual cycle do humans ovulate?

Answer 10

14

Question 11

What happens during ovulation? Hormone changes, uterine lining changes

Answer 11

• 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

Question 12

What is the receptive state of the menstrual cycle? how long is it

Answer 12

State of the uterine lining ready for implantation, days 20-24, 7-10 days in secretory phase

Question 13

What are the principal pathways of steroidogenesis in follicular cells?

Answer 13

Theca cell is producing substrate that is being released to granulosa cell and then that makes the oestrogen.
Check L4, SLIDE 9 for diagramm

Question 14

What are the potential targets to disrupt the fertility of the human menstrual cycle (contraception)?

Answer 14

Fertility relies upon co-ordinated interactions between Hypothalamic-Pituitary-Ovarian axis, ovary and uterus –> targets
- folliculogenesis
- ovulation
- embryogenesis
- estrogen
- LH, FSH
- Progesterone
- Receptive state

Question 15

What is the combined contraceptive pill?

Answer 15

combination of an oestrogen and a progesterone analogue, taken 21 of 28 days

Question 16

What is the mechanism of combined contraceptive pill?

Answer 16

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

Question 17

What are the side effects of combined contraceptive pill?

Answer 17

• nausea and vomiting
• weight gain
• loss of, or increase in, libido
• peripheral thrombosis (risk increases with age and smoking)
• prevents lactation

Question 18

What is the failure rate of combined contraceptive pill?

Answer 18

• ‘perfect’ use 0.3% (e.g. randomised controlled trial)
• in ‘real life’, 2-8%

Question 19

What are the examples of combined contraceptive pill?

Answer 19

• many different formulations of synthetic progesterone (e.g. levonotgestrel) and oestrogen (e.g. ethinylestradiol)
• microgynon 30 (Schering)
• Logynon (Schering)
• Marvelon (Organon)
• Femodene (Schering)

Question 20

When are progestogen-only contraceptives used?

Answer 20

• For older women,
• heavy smokers,
• patients with history of venous thrombosis, hypertension, diabetes mellitus

Question 21

What is the available medication as progestogen-only contraceptives?

Answer 21

• daily progesterone as a pill (levonorgestrel)
• depot i.m. every 3 months (medroxyprogesterone acetate)
• implant (etonogestrel in implant 3 years)
• intrauterine (IUDs) (levonorgestrel release)

Question 22

What are the actions of progestogen-only contraceptives?

Answer 22

• endometrium less receptive
• cervical mucus thicker and hostile to sperm
• may affect follicle development

Question 23

What is important to know when using progestogen-only contraceptives?

Answer 23

• timing more important - take at the same time each day - don’t affect ovulation so protection window is shorter

Question 24

What are the side effects of progestogen-only contraception?

Answer 24

• menstrual irregularities, although these usually resolve
• some really don’t get on well, and they get sort of prolonged light blood flow

Question 25

What is **emergency contraception**?

Answer 25

- Progesterone only contraception, within 72 hours, and again 12 hours later - more effective if taken earlier

Question 26

How is fetal adrenal gland important in pregnant sheep?

Answer 26

- 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

Question 27

How is fetal adrenal gland important in pregnant sheep?

Answer 27

cortisol stimulates the 17alpha-hydroxylase, which allows the substrate to move from progesterone through synthetic pathway, which ends up in oestrogen production

Question 28

What are the two types of steroid hormone action?

Answer 28

- 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