REPRO - Endocrine Flashcards
What hormone does inhibin decrease and activin stimulate?
FSH
Where are the sex steroids E2 and P4 (progesterone) made?
(Gonads) The ovarian follicle
Kisspeptin neurones send projections to …
Causing…
GnRH neurones onto kisspeptin receptor
–> synthesis/release of GnRH
To where does the superficial hypophyseal arteries deliver blood to?
-the capillary network in upper infundibulum
To where do the portal vessels deliver blood with regulatory hormones to?
to the capillary network in the ANTERIOR pituitary
To where does the inferior hypophyseal arteries deliver blood to?
-to the POSTERIOR pituitary
To where do the hypophyseal veins deliver blood to?
to the CVS with pituitary hormones for delivery to the body
What is GnRH (10a.acids) secreted with?
GnRH Associated Peptide (GAP) (56a.acids)
GnRH pulses are every 30-120mins and they stimulate…How?
LH/FSH release from pituitary
-increases gene transcription of a and B subunits of LH/FSH on the pituitary gonadotrophs
What does fast pulse frequency of GnRH favour?
LH
What does slow pulse frequency of GnRH favour?
FSH
How is synthetic GnRH uses clinically?
-stimulates HPA axis in the form of a timed pump e.g. for delayed puberty
GnRH agonists given continuously have what effect?
downregulate response as they decouple the GPCR so less FSH/LH
3 examples of when GnRH agonists may be used (receptor becomes unresponsive so less FSH/LH)
- ovulation induction, IVF,
- endometriosis, uterine fibroids,
- prostate cancer,
- gonadal protection from chemo
Gonadotrophins are heterodimeric peptides, name 3, they all have 2 subunits, what are they?
-LH/FSH/hCG
-common alpha, specific beta subunit
(a made in excess, B synthesis limits hormone conc
What do all the alpha subunits have in common?
glycosylated and have N-linked carbohydrate side chains (O-linked in hCG)
Male: LH acts on receptors where to do what?
On leydig cell receptors of testis to convert more cholesterol to increase androgens
What do androgens in the testis cross over and stimulate?
Sertoli cells to control spermatogenesis
Where does FSH act on receptors in males..to convert..?
Sertoli cells to convert androgens into more oestrogens
What 2 effects does LH have in the female?
- increases Theca cell androgen synthesis during follicular phase to mediate ovulation
- stimulates progesterone production from CL
What 2 effects does FSH have in the female?
- causes follicular maturation
- enables granulosa cells to make oestrogen from androgens under aromatase
What 3 mood/behavioural effects does testosterone have?
- boistrous play
- enhances sex drive
- aggression
What effect does DHT (converted via 5a reductase) have on hair? Hence clinically..
Promotes hair loss, so male pattern baldness treatments include 5a reductase inhibitors
Where is TYPE I vs TYPE II 5a Reductase?
TYPE I - Scalp and Skin
TYPE II - Genital skin and Prostate
What happens in 5adr? (5a reductase deficiency)
- testes develop but no prostate
- ext. genitalia are female
- clitoris enlarges may get penis at 12 S.
What is male pseudohermaphoditism a condition that is a mutation in what? Common in Dominican Republic
-mutation in TYPE II 5a reductase
5 Unwanted effects of excessive androgens? eg. testosterone, DHT, nandolone, oxymetholone, stanozolol
1. -Gynaecomastia as aromatase converts it to oestrogens
- HT and oedema as Ca2+/Na+/H20 retaining
- cholestatic jaundice
- supressed GnRH (neg feedback) so testicular regression and less spermatogenesis
- virilisation and hirsuitism, baldness, acne
- premature closure of long bone epiphysis
Name 2 psychological changes in excessive androgen intake for example anabolic steroid abuse by athetes to increases muscle mass
-change in libido
-increased agression
NB: They are also hepatotoxic and can cause vascular disease
What does the enzyme 21 OH convert progesterone into mainly? What builds up with a deficiency in this enzyme?
Aldosterone
-progesterone shunted to DHEA and androstenedione
What are the effects of 21OH deficiency (CAH) increasing DHEA and androstendione on cortisol and testosterone hence..?
- lack of cortisol so more ACTH and more cholesterol uptake in adrenal
- adrostenedione –> more testosterone so excess male hormones (virilises XX) and adrenal hyperplasia
CAH in XX causes ambiguous genitalia and acne, what does it cause in XY?
- precocious deep voice
- enlarged penis
- small testes
- pubic hair
What are Cyproterone, Danazol and other androgen antagonists used to treat?
Exccess androgens for example in CAH
What is Gonadorelin administered by a pump.
It is synthetic GnRH
GnRH agonist analogues such as goserelin and buserelin are useful in prostate and breast cancer and endometriosis. How do they work?
- cause an initial LH/FSH rise
- remain bound to gonadotroph receptors
- desensitisation so less testosterone
What are GnRH antagonist like Cetrorelix and Ganirelix used to control?
- control LH secretion in IVF
- for prostate and breast cancer
Mesterolone (Methyltestosterone) is used to treat male what?
Male infertility associated with hypogonadism
In partial AIS with impaired masculinisation of the genitalia, and lack of secondary sexual characteristics what may be given?
DHT, testosterone
What is Danazoll’s mechanism? It is used for gynaecomastia, mastalgia, endometriosis and benign fibrocystic disease.
Danazol is an androgen derivative which is not converted to oestrogen so it inhibits testicular and ovarian function e.g. stops ovulation
What is a possible chromosomal cause of 1ry hypogonadism?
Klienfelters 47XXY low testosterone levels, less neg feedback so FSH and LH are high
What is a syndromic cause of 2dry hypogonadism. May be due to low GnRH secretion hence low LH/FSH
Kallman’s Syndrome
In Kallman’s syndrome, what hormones may be given to correct the delayed puberty/infertility?
Gonadorelin or LH/FSH
Give 3 uses for the androgen antagonist ‘cyproterone acetate’ that inhibits peripheral androgen receptors
- male precocious puberty
- supress Goserelin/Buserelin initial surge
- for acne, hirsuitism, virilisaiton of females
- in CAH
What type of prostate cancers can œstrogens like Ethinyloestradiol and diethylstilbestrol treat?
Androgen dependent prostate cancers
5a reductase inhibitors also supress these
Dutasteride is a TYPE I and TYPE II 5a reductase inhibitor, what about Finasteride? Where does it work?
- Finasteride is only TYPE II 5a r. Inhibitor
- only genital skin and prostate action
