L01: HPG Axis Flashcards
What is the HPG axis
Hypothalamus pituitary gonads axis
What hormone does the hypothalamus release in females and males
GNRH
Where does GNRH act in the head
Anterior pituitary gland
What does the anterior pituitary gland release to the gonads in female and male
LH
FSH
What are the female gonads
Ovary
What are the male gonads
Testis
What hormone does the testis produce
Inhibin
Testosterone
What hormone does the ovary produce
Oestrogen
Progesterone
What happens to the gonads at puberty
They are activated
How is GNRH triggered
A pulsatile secretion
Why is it important to have pulsatile release of GNRH and not a continuous release
A continuous release of GNRH leads to down regulation of GNRH receptors
Where are GNRH receptors found
In the surface of gonadotroph cells in the anterior pituitary gland
What would happen to the levels of FSH/LH if there was a continuous flow of GNRH
No stimulation of FSH and LH
What other hormones does the anterior pituitary gland release
Acth Tsh Gh LH FSH Prolactin
What hormone does the posterior pituitary gland release
ADH
Oxytocin
What does FSH stand for
Follicle stimulating hormone
Luteinising hormone
What is the third important gonadotropin but not produced in the pituitary gland called
HCG
What type of substances are gonadtrohps
Glycoproteins
What type of receptors does glycoproteins bind to
GCPRs
What cell is LH and FSH secreted by
Gonadotrophs
What cell is HCG secreted by
Trophoblast cells in the embryo
What type of cells does LH act on
Leydig
Theca
Granulosa cells
What type of cells does FSH act on
Sertoli
Granulosa cells
What type of cells does HCG act on
Luteal cells in the corpus luteum
In the 3 gonadotrophs what is a similarity in their structure
All have alpha chains that are similiar
What are the differnces in the 3 gonadotrophs
Beta chains differ
How is the beta chain of LH and HCG
They differ very small compared to FSH
What receptor does LH bind to
LHCGR
What receptor does FSH bind to
FSHR
What receptor does HCG bind to
LHCGR
How does the hypothalamus and anterior pituitary gland communicate
Indirectly via vasculature
What is the role of gonads
To produce sex steroids and other regulatory factors e.g inhibition
What type of feedback does the hormones release by the gonads create
Regulatory feedback
What molecule are all steroids derived from
Cholesterol
What are the 3 families of sex steroids
Progesterone
Androgens
Oestrogen’s
What is the feedback in the males called
Negative feedback loop
What is the feedback in females like
More complicated, (will be explained in detail later)
What role does progesterone play a role in
In pregnancy
Where is progesterone produced
Ovaries
Placenta
What type of role does androgen have
Maleness (but also produced in the female)
Where are androgens produced
Gonads
Adrenal glands
What role does oestrogens play
Femaleness ( and some male)
Where are oestrogen produced
Ovaries Testis Liver Adrenal glands Adipose Placenta
Are sex steroid lipid soluble or lipid insoluble
Lipid soluble
If sex steroids are lipid soluble what does it mean in terms of the plasma membrane of a cell
It can pass into the cell
When sex steroids pass into the cell what receptors do they bind to
Nuclear receptors
What do the sex steroids act on the nuclear receptros via
Steroid response elements
If sex steroids are lipophilic what does this mean in terms of them being solution
They cannot be in solution
To allow sex steroid hormones to be in solution what are they bound to
Sex hormone binding globulin
What is sex hormone binding globulin
A carrier protein
Name another carrier protein that is present in the testis
Androgen binding protein
How are sex steroids produced
Progesterones form androgens
Androgens form the oestrogens
How many forms does progestagens have
3
Name the 3 forms of progestagens
Progesterone
17alpha-hydroxyprogesterone (17a-OHP)
20alpha-hydroxyprogesterone (20a-OHP)
What happens to potency of the progestagens as you go from progesterone to 20a-OHP
Decreases
What are the receptors of the progestagens
PR-A
PR-B
How many forms of androgen are there
4
Name the 4 forms of androgen
5alpha-dihydrotestosterone (DHT)
Testesterone
Androstenedione (A4)
Dehydropiandrosterone (DHEA)
What receptors do androgens binds to
AR
What happen to the potency of androgens as you go from DHT to DHEA
Decrease
How many forms of oestrogen are there
3
Name the forms of oestrogen
Oestradiol 17beta (E2)
Oestriol (E3)
Oestrone (E1)
What are the receptors of oestrogens
ER-alpha
ER-beta
What happens to the potency of oestrogen as you go from E2 to E1
Decreases
How does the predominant form of oestrogen vary within the female lifecycle
Puberty to menopause: oestradial (E2)
Pregnancy: oestriol (E3)
Post menopause: oestrone (E1)
What is potency
How well it binds to its receptors
What are the 2 ways that we can regulate steroid action
1) alter amount of steroid produced
2) alter amount or structure of receptors
What is central hypogonadism
Low FSH/LH due to a problem in the hypothalamus or pituitary i.e central because it cannot produce it
What is primary hypogonadism
High FSH and LH because the gonads are not responding to FSH/LH and so are not producing the sex steroids to inhibit it causing lack of feedback.
what role does prolactin play a role in
Breastfeeding
When does prolactin increase
During pregnancy
What doe high levels of prolactin do to the HPG axis
Supress it
If the HPG axis is suppressed what happens to LH/FSH
Decreases
What is lactational ammenrrhoea
Absence of periods due to breastfeeding
What is abnormal increases in prolactin called
Hyperprolactinemia
What can hyperprolactinemia cause
Galactorrhea
What is galatactorrhea
Production of breast milk when you are not pregnant
Is the gametogenesis in males continous or cyclic
Continous
Is gametogenesis in females continous or cyclic
Cyclic - one oocyte released per month
What are the 3 phases of the menstrual cycle in females
Follicular
Ovulation
Luteal/secretory
What is the normal duration of the menstrual cycle
26-32 days
How long does the luteal phase last
14 days
Which phase of the menstrual cycle varies that determines the length of the menstrual cycle
Follicular phase
What is day 1
First day of period
What is oligomennorhea
Less than 9 cycles in the last 12 months
What is ammenorhea
No bleed in the last 6 months
What are 2 types of ammenorhhea
Primary
Secondary
What is primary ammenorhhea
Never had periods
What is secondary amennorhea
Had periods but stopped for some reason
What is mennorhagia
Heavy period
What is dysmenorrhea
Painful periods
Around what age does a female experience menopause
50
Why does a lady get menopoause
Ovarian reserve is depleted
What happens to the LH/FSH levels
High
Why is there high FSH/LH in menopause
Due to loss of negative feedback by sex steroids
What are hormonal contraception
Progestagens
Oestrogen
What does progesterone and oestrogens do
Supress ovulation
Thickens cervical mucus
Thins endometrium
What does fertility treatment involve
Down regulate the HPG axis with GNRH agonist/antagonist
How do we treat prostate cancer
GNRH antagonist to suppress T production
