HPG axis Flashcards
Which two sex steroids are produced in the testis?
Inhibin and testosterone
Which two sex steroids are produced in the ovary?
Oestrogen and progesterone
What hormone is released by the hypothalamus?
GnRH - decapeptide from 92 AA prepropeptide
What is the characteristic of GnRH secretion at puberty and what is its function?
Pulsatile to activate the gonads
What happens if GnRH is continuously released?
Causes a downregulation and internalisation of GnRH recpetors on gonadotroph cells preventing LH/FSh release.
How can GnRH be used in fertility treatment?
Can use a GnRH antagonist or a GnRH agonist as the peak causes downregulation
What condition results from a failure of GnRH secreting neurons to migrate during development?
Kallmann Syndrome = infertility
Which hormones are released in the pituitary as a result of GnRH and where are they released from?
GnRH stimulates the anterior pituitary indirectly via vascular beds to release gonadotrophins from the gonadotrophs to act on the gonads. They release LH and FSH
Where is hCG produced?
A gonadotrophins produced by embryonic trophoblasts
How do gonadotrophins signals?
Bind to cell surface receptors and signal via GPCR.
Where does LH act?
On LHCGR of:
Leydig cells in testes
Theca and granulosa cells of ovary
Where does FSH act?
On FSHR of:
Sertoli cells in testes
Granulosa cells of ovary
Where does hCG act?
On luteal cells of the corpus luteum
What is the difference between the structure of LH compared to FSH and hCG?
All have a common alpha chain, a unique beta chain. LH has 1 carb chain and the others have 2 chains.
What is the difference between the HPG axis feedback in males and females?
Males always have -ve feedback where as women have both +ve and -ve.
What are sex steroids derived from ?
Cholesterol via acetate.
Where are progestagens released from?
Ovaries and placenta
Where are androgens released from?
Testes mainly, adrenal gland and ovaires
Where are oestrogens released from?
Ovaries, liver, adipose, adrenal, placenta in both males and females.
How are sex steroids transported and where is their receptor?
As they are lipid soluble and act on intracellular receptors via steriod response elements, they are bound to carrier proteins such as albumin, sex hormone binding globulin (HBG) and androgen binding protein (ABP) from testes.
Which sex steroids are produced first?
Progestagens then androgens then oestrogens
What determines the potency of the steroid?
How well it binds to the receptor. It varies due to the chemical structure of each class.
Some steroids can bind receptors from another class. What will result from COC binding to androgen R?
Causes androgeneric action resulting in acne
What is the use of mifepristone?
An anti-progestagen acting as an antagonist to terminate pregnancy.
What are the 3 types of progestagens and their functions?
Progesterone - Preparation and maintenance of uterus
17alpha OHP - Growth of mammary glands during pregnancy
20alpha OHP - Suppresses lactation and regulates gonadotrophins
What are the receptors for progestagens?
PR-A and PR-B. Each activates different genes
What are the 4 types of androgens and what is their function?
DHT - Development and maintenance of male reproductive system
Testosterone - Secondary sexual characteristics
Androstenedione - Sexual function and support
DHEA - Spermatogenesis and regulation of gonadotrophins
At what receptor do androgens act?
AR - have varying isoforms for different sensitivities to androgen levels
Name the 3 types of oesrtogens and their fucntions.
Oestradiol - Puberty to menopause. Secondary sexual characteristics and mammary gland growth and activity.
Oestriol - Pregnancy. Proliferation of endometrium for progesterone action
Oestrone - Post menopausal. Regulates gonadotrophins.
At which receptors do oestrogens act?
ERalpha and ERbeta
How is the amount of steroid or the amount/structure of receptor controlled?
Via feedback loops
What information is not gained from measuring hormone levels?
Structure of receptors
What is central hypogonadism?
LOW FSH and LH causing low gonad function. Arises due to a problem with the hypothalamus or pituitary
What is primary hypogonadism?
Failure to produce sex steroids and therefore a loss of feedback resulting in HIGH FHS and LH. Due to a problem with the gonads.
Why is GnRH not measured when investigating fertility?
It has a pulsatile nature and a short half life
What is the effect of prolactin on the HPG axis during pregnancy?
High prolactin levels in pregnancy and breast feeding inhibit gonad activity by suppressing GnRH release, keeping FSH and LH levels LOW.
How is prolactin used as a contraceptive method after parturition? How effective is this method?
Prolactin suppresses HPG axis to induce lactational amenorrhea. It is 98% effective with contiuous breast feeding and no formula.
What is the result of hyperprolactinaemia outside of pregnancy?
Galactorrhea - discharge unrelated to breast feeding.
What is the difference between male and female gamete production?
Males gametogenesis is continuous bbut female is cyclic, producing one oocyte every month.
What are the 3 stages of the menstrual cycle?
Follicular, ovulation and luteal/secretory (day 14)
On which day of the cycle do menses begin and on which day is ovulation?
Day 1 menses
Day 14 ovulation
On which day should the levels of LH and FSH be measured? What does the level of FSH indicate?
Day 2/3
FSH shows the ovarian reserve - how many oocytes and for how long
On which day should progesterone be measured and what does it provide an indication of?
Day 21/28 to show ovulation
What is oligomenorrhea?
<9 cycles in 12 months
What is amenrrhea?
No bleeding for 6 months.
Primary = never had a period
Secondary = Ceased periods
What is menorrhagia?
Heavy bleeding
What is dysmenorrhea?
Painful bleeding
What happens to the hormone levels at menopause?
When ovarian reserve is depleted and ovulation ceases, progesterone and oestrogen production by the ovary stops. This removes the negative feedback and causes LH and FSH levels to RISE.
How can fertility treatment be used to treat prostate cancer?
Use GnRH antagonists to suppress Testosterone production
