Reproductive Endocrinology Flashcards
What are hormones found in the ovary?
Oestrogen and progesterone
What happens to the water soluble hormones?
They can float around in the bloodstream but need to enter through G-protein receptors into the cells via ATP and cAMP mechanisms. Once within cells they cause a cascade through protein kinase phosphorylising enzymes of interest. This causes the response in the cell.
How do lipid hormones enter the cell?
They need a transport protein to travel around the blood but can diffuse into the cells directly. They then activate receptor hormones in the nucleus changing the gene expression. This newly formed mRNA creates new proteins
What are the actions of gonadotropins - males?
FSH and LH travels from pituitary to the gonads where they act. FSH acts in the serotoli cells to help support soerm. They LH works on the leydig cells which can secrete testosterone
Actions of the gonadotropins - females?
LH works on the Theca cells to make androstenedione. Astrostenedione works with FSH in the granulosa cell to make estradiol.
FSH works on the granulosa cells to make Estradiol.
What is the actions of testosterone?
Male reproductive function e.g make sperm
Secondary make characterus5uce
Make sex determination and genital development.
What are the actions of oestradiol?
Endometrial proliferation during menstrual cycle
Female genital development
Secondary female sex characteristics
What does progesterone regulates?
Endometrial secretion and vascularisation during menstrual cycle
Maintains pregnancy and support embryo
What do Hormonal contraceptions do?
Manipulation of steroid gonadal hormones
What does hormonal contraceptives do in females?
Suppress ovulation via negative feedback of progesterone
Oestrogen in combined pill provides additional feedback and promotes progesterone receptor expression
Secondary effects on female genital tract
What does hormonal contraceptive in males do?
Suppress spermatogenesis via negative feedback of testosterone
What happens if you stop taking contraception?
Own HPG axis reawakens
Negative feedback in HPG axis?
Gonadotropin releasing hormone from the hypothalamus causes release of LH and FSH from pituitary which act in the ovary. Oestrogen, progesterone and androgens act back in the pituitary and hypothalamus to reduce secretion of LH/FSH/GnRH
What is positive feedback in HPG axis especially in the sertoli and granulosa cells?
Activins are hormones produced by Sertoli cells and granulosa cells which encourage FSH secretion from anterior pituitary
How is positive feedback happening when a follicle grows?
Follicles growing produce more oestrogen which at certain thresholds had a positive affect in FSH secretion and the LH surge
What is the positive feedback when a pregnancy happens?
The blastocyst makes HcG so causes FSH to rise and LH, progesterone to increase.
How does lactation work?
Baby suckles at teat and this sends nerve impulses to the brain causing oxytocin (from posterior pituitary) and prolactin (from anterior pituitary) to be released.
What does prolactin do?
Causes alveoli to swell and secrete milk. There is however a steroid block from placenta preventing lactation before birth. There is a negative feedback on FSH/LH levels
What does oxytocin do?
Causes smooth muscle contraction of the myoepithelial cell around the alveoli making milk eject. This also induces labour
What is the anti-mullarian hormone?
Critical for sex determination in male embryos
What activates AMH?
Sox9 in Sertoli cells which inhibits the development of the Müllerian duct which would normally make fallopian tubes, vagina, uterus etc.
Where is AMH made in females and what does it inhibit/ unaffected by?
Made in granulosa cells and inhibits follicular development. It is unaffected by gonadotropins/steroid hormone
Why is AMH used clinically?
It’s a reliable way to reflect growing follicles
What is the fundamental way to tell how fertile you are?
Primordial follicles but there is no way to measure this
What releases GnRH?
Neurones in the hypothalamus
Where is GnRH released to?
Pulsatile released into hypophyseal portal system
What does GnRH release to the hypophyseal portal system do?
Prevents receptor desensitisation and downregulation
Why is GnRH important?
There is a surge just before ovulation and is important for timing of puberty and menstrual cycle.
If GnRH is released quickly what hormone does this affect?
FSH
If GnRH is released slowly what hormone does this affect?
LH
How does GnRH respond to the ovarian hormonal feedback because it does not have any receptors?
Kisspeptin signalling pathway
What is kisspeptin essential in?
Puberty, gonadotropin secretion and regulation of reproduction, sexual and social behavious, emotional brain processeing, mood, audition etc.
What gene controls the kisspeptide?
KiSS1
What is the kiss1 receptor and where is it found?
KiSS1 receptor is a G-protein coupled receptor found on KiSS neurons in hypothalamus.
What is the experimental evidence to confirm Kisspeptin is involved in reproduction endocrinology? (4)
- Kisspeptin causes depolarisation and increases firing in GnRH neurones
- Stimulates secretion of GnRH in hypothalamic explant cultures
- GnRH mRNA upregulated in GnRH neurones after exposure to Kisspeptin.
- Kisspeptin can directly stimulate pituitary gonadotropes to release LH/FSH but this is probably secondary
What happens in KiSSR mutations?
- There are puberty disorders in humans e.g. Inactivating mutations (delayed puberty), activating/missense mutations (precocious puberty).
The kisspeptin signalling pathway - is kisspeptin neurones located in different locations in the rodent brain and human brain?
The kisspeptin neurones are found in different locations in rodents VS humans.
What do KiSS neurones release?
KiSS neurones only release KiSSpeptin
What do KDNy (candy) neurones release?
KDNy neurones release KiSS and neurokininD and Dynorfin.
What do KDNY neurones do?
These can help regulate Kisspeptin and also have eostrogen receptors so are involved in the negative feedback which would decrease GnRH.
Can KiSS neurones take information from more than one body location than just the gonads?
Yes - body fat, adrenal gland (cortisol - this is why stress can affect your period), environmental cues and immune cells.
What does Kisspeptin do in males?
Secretes LH and testosterone production although there is no KiSS receptors on testosterone.
Is testosterone aromatised before binding to ER alpha on KiSS neurones?
Yes
What is the only neurones that can cause the LH surge?
AVPV neurones
What exposure is important in utero to determine gender of neurones?
Sex steroids
Are we starting to manipulate KiSS signalling?
Yes because this can change LH which could be very helpful to some women suffering from these conditions
What is hypogonadism?
Gonads producing too little hormones
What does Hypogonadotropic mean?
Problem with pituitary or hypothalamus
When would you diagnose hypogonadotropic hypogonadism?
In males - newborns due to micropenis, cyrptochodism
In females - at puberty
What are causes of hypogonadotropic hypogonadism?
Structural lesions in pituitary/hypothalamus area
Congenital e.g. mutations
Acquired infection, trauma, drugs, tumours etc.
Functional (usually reversible) e.g. diet, over-exercise, stress
What is the treatment of hypogonadotropic hypogonadism?
HRT
What is PCOS?
Heterogenous condition with the symptoms of oligo/anovulation, evidence of hyperandrogenism or polycystic ovaries.
What is the cause of PCOS?
High LH low FSH
Increase androgen production from follicle
Excess androgens cause cystic ovaries
Increased weight
Insulin augments theca cells and androgen production
Vicious cycle between insulin and weight gain
How do you manage PCOS?
Lifestyle changes, metformin, HRT
What is premature ovarian insufficiency (POI)?
Menapause before the age of 40 charecterised by amenorrhea, hypoestorgenism and loss of fertility.
Diagnosis of POI?
Hihg LH, high FSH, low oestrogen
Causes of POI?
Genetic, iatrogenic, autoimmune
Treatment of POI?
HRT however no treatment allows pregnancy only donor eggs/ adoption.
