HPG Axis Flashcards
What is the HPG axis in women?
hypothalamus (GnRH) –> a. pituitary (LSH/FH) –> ovary (oestrogen/progesterone)
- oestrogen provides negative/positve feedback to a.pituitary
- progesterone provides negative feedback to a/pituitary
What is the HPG axis in men?
hypothalamus (GnRH) -> a. pituitary (FSH/LH) –> testis (inhibin and testosterone)
- inhibin and testosterone provide negative feedback to a. pituitary
What is the hypothalamus?
What does it control?
region found at the base of the brain between midbrain and forebrain
collection of brain nuclei or centres
controls endocrine function via pituitary gland
What is the hormone released from the hypothalamus on the HPG-axis?
GnRH
gonadotropin releasing hormone
What type of hormone is GnRH?
What is Kallmann Syndrome?
a peptide hormone. decapeptide, from a 92 aa prepropeptide
Kallmann Syndrome = failure of GnRH secreting neurones to migrate during development –> infertility
What kind of GnRH secretion triggers gonadal activation
pulsatile GnRH secretion at puberty
What is the effect of continuous GnRH secretion?
leads to down regulation of GnRHR on surface of gonadotroph cells - no stimulation of FSH/LH release
It is possible to block GnRH effects using an antagonist and an agonist. TRUE/FALSE
TRUE
What is secreted by the pituitary gland?
LH/FSH GH ACTH FSH Prolactin
ADH
oxytocin
What are the 3 gonadotropins?
What kind of hormones are they?
How do they interact with their target cells?
FSH LH hCG
glycoproteins
bind receptors on cell surface and signal via GPCRs
LH:
- what is it secreted by?
- what cells does it act on? where are these cells?
- what is its structure?
- what is its receptor?
- gonadotrophs (a. pituitary)
- leydic cells (testis), theca/granulosa cells (ovary)
- common alpha chain, unique B chain, one carb chain
- LHCGR
FSH:
- what is it secreted by?
- what does it act on?
- what is its structure?
- what is its receptor?
- gonadotrophs (a.pituitary)
- sertoli cells (testis), granulosa cells (ovary)
- common alpha chain, unique B chain, two carb chains
- FSHR
hCG:
- what is it secreted by?
- what does it act on?
- what is its structure?
- what is its receptor?
- trophoblast cells (embryo)
- luteal cells (corpus luteum)
- common alpha chain, unique B chain, two carb chains
- LHCGR
What are the two forms of communication between the hypothalamus and pituitary?
Direct i.e. neural to posterior pituitary
Indirect i.e. vascular to anterior pituitary
Where are all sex steroids derived from? and via?
What are the characteristics of sex steroids?
What do they act on?
What are they bound to in the blood?
all derived from cholesterol (via acetate)
lipid soluble, nuclear receptors
act via steroid response elements (SREs)
bound to carrier proteins - albumin, sex hormone binding globulin (SHBG), androgen binding protein (ABP)
What are the 3 families of sex steroids?
What are they responsible for?
progestogens - pregnancy (plancenta/ovary)
androgens - maleness
oestrogens - femaleness (liver, adrenals, adipose, placenta)
What is the order of cleavage for the 3 classes of sex hromenss?
progestogens
androgens
oestrogens
What are the 3 progestogens?
Progesterone (P4)
17a-hydroxyprogesterone (17a-OHP)
20a-hydroxyprogesterone (20a-OHP)
What are the reproductive functions progestagens?
- preparation of uterus
- maintenance of uterus during pregnancy
- growth of mammary glands
- suppression of lactation
- catabolic effects
- regulation of gonadotrophin
What are the receptors for progestagens?
PR-A and PR-B
activate different genes
What are the 4
androgens?
5a-dihydrotestosterone (DHT)
testosterone (T)
androstenedione (A4)
dehydroepiandrosterone (DHEA)
What are the reproductive functions of androgens?
- development and maintenance of male reproductive system
- secondary sexual characteristics
- sexual function
- support spermatogenesis
- regulation of gonadotrophins
What are the receptors for androgens?
AR
polymorphoc in exon 1 with isoforms showing differing sensitivities to androgen levels
What are the 3 oestrogens?
oestradiol 17B (E2)
oestriol (E3)
oestrogen (E1)
What are the reproductive functions of oestrogens?
- secondary sexual characteristics
- stimulate growth and activity of mammary glands
- stimulation proliferation of endometrium fro progesterone action
- regulate gonadotropins
What are the receptors for oestrogens?
ERalpha and ERbeta
Which of the 3 oestrogens are dominant in each of the following:
- puberty to menopause
- pregnancy
- post-menopause
- puberty to menopause = oestradiol
- pregnancy = oestriol
- post-menopause = oestrone
What determines potency?
depends on how well steroid ‘fits’ binding site on receptor
Some steroids fit receptors from other classes. Give an example
synthetic progestogens in contraceptive pill can be androgenic - side effects e.g. acne
Some steroids bind but don’t activate. Give an example
act as antagonists e.g. Mifepristone (RU486)
- anti-progestogen / abortion pill
In what two ways can steroid action be regulated?
How does this affect measuring hormone levels?
- alter amount of steroid produced
- alter amount or structure of receptor
- sex steroids are both regulated by and regulate gonadotrophin of the anterior pituitary via feedback loops
- only measuring hormone levels will not give complete picture
What is central hypogonadism?
What is primary hypogonadism?
central - hypothalamus/pituitary –> low FSH/LH
primary - ovary/testis –> high FSH/LH
Why is GnRH rarely measured?
pulsatile and short halflife
What are the functions of prolactin?
- stimulates milk production
- inhibits gonadal activity through central suppression of GnRH (and thus decreased LH/FSH) –> induces lactational amenorrhea
What are the 3 phases of the menstrual cycle?
follicular/proliferative
ovulation
luteal/secretory
What is the normal duration of the menstrual cycle?
What is the normal duration of luteal phase?
When is Day 1?
When is FSH/LH tested for?
When is ovulation tested?
26-32 days (28 days) 14 days first day of menses day 2 or 3 P4, tested on day 21
What is oligomenorrhea? What is primary amenorrhea? What is secondary amenorrhea? What is menorrhagia? What is dysmenorrhea?
irregular periods no bleed ever no bleed in last 6 months heavy periods painful periods
What is menopause?
females are born with a finite number of oocytes
around the age of 50, ovarian reserve is depleted and ovulation ceases
no production of progesterone or oestrogen by ovary
removal of negative feedback leads to high FSH/LH levels
How does hormonal contraception work?
synthetic progestogens and oestrogens - suppresses ovulation, thickens cervical mucus, thin endometrium
How does fertility treatment work?
IVF –> ovarian stimulation
down regulate HPG axis with GnRH agonist/antagonist. stimulate with FSH, induce oocyte maturation with hCG
What is the treatment for prostate cancer?
GnRH antagonists to suppress T production
