Reproductive Hormones Flashcards
Basic Physiology and Functions of LH/FSH
GnRH secreted episodically (1-2h) –> LH/FSH
LH/FSH are glycoproteins constructed on 2 polypeptide subunits
- -> alpha common to both (as with TSH, hCG)
- -> beta unique
LH
- male: leydig cells secrete testosterone (negative feedback on LH)
- female: surge causes ovulation, development of corpus luteum, stimulates progesterone secretion, production of androstenedione and testosterone at theca cells
FSH
- male: sertoli cells secrete androgen binding protein and sustain spermatogenesis (inhibin negative feedback)
- female: develops ovarian follicles, stimulates estrogen secretion (aromatisation of androstenedione and testosterone at granulosa cells)
Recall androgen synthesis pathway
Zona reticularis
Pregnenolone –> 17-OH pregenenolone –> DHEA –> Androstenedione –> testosterone or estrone –> estradiol
Testosterone –> DHT by 5 alpha reductase
DHEA –> DHEAS (or vice versa) by sulphokinase
Production of androgens in male
Potent androgens:
- testosterone (from testes) and dihydrotestosterone (conversion from T by 5 alpha reductase at target sites)
Weak androgens:
- DHEAS, androstenedione from adrenal glands
- requires conversion to T and DHT to express androgenic effect in peripheral tissues
Androgen actions (male)
Intracellular receptors (specific response elements in nucleus)
- Masculinisation of male foetus in before 10th wk
- stimulate development of secondary sexual characteristics after puberty e.g. penis, axillary/pubic/body hair, muscles, deepening of voice, bone growth etc.
Testosterone
- foetus: internal genitalia including Wolffian duct
- puberty: initiate spermatogenesis, psyochosexual behaviour, muscle, voice
DHT
- foetus: external genitalia
- puberty: prostate development, male pattern hair growth
Androgens in female (sources)
Testosterone (10% of male levels)
- from ovaries, adrenal glands
- 50% from circulating androstenedione
DHEA
- adrenal glands (95%)
Androstenedione
- 50% ovaries, 50% adrenal glands
==> essential precursor for oestrogen’s
==> bone growth and libido
Menstrual cycle
- Low levels of estrogen/progesterone at the beginning of cycle (shedding) –> less inhibition on FSH –> increase FSH
- FSH stimulates follicles to grow which secrete increasing estrogen
- Endometrium thickens and builds up due to estrogen
- During late follicular phase, high and rising estrogen stimulates LH surge with positive feedback
- Ovulation
- Under the influence of LH, progesterone is secreted by corpus luteum and peaks at day 21
- Progesterone converts endometrium to secretory form to prepare for pregnancy
- Increase progesterone = negative feedback on LH
- Suppressed LH = can’t maintain corpus luteum
- Regression of corpus luteum = progesterone decreases
- Decrease in steroids = disintegration of endometrium –> menses
(if ovum is fertilised, hCG from trophoblast takes over corpus luteum stimulation with continuous steroid production to maintain pregnancy during 1st 3 months)
Estrogen types, functions
Oestrone (E1) = from peripheral aromatisation of androstenedione
Oestradiol (E2) = most potent – from ovaries and testes, aromatisation of testosterone
Oestriol (E3) = during pregnancy
Functions
- secondary sex characteristics in females
- regulation of menstrual cycle
Mature follicle –> 1000-1500 pmol/L oestradiol
Peak just prior to ovulation followed by second minor peak during ensuing luteal phase
Sex hormone binding globulin
Major carrier protein for T and E2, produced mainly by liver with high affinity (T>E2)
Plasma levels increased by oestrogen and thyroxine, decreased by androgens
T:SHBG ratio (%) i.e. free androgen index indirectly reflects free T levels (though it tends to overestimate and doesn’t consider albumin-bound fraction)
<3% hormones circulation in free form, 40% weakly bound to albumin (also considered active)
==> free and albumin bound testosterone = bioavailable testosterone
Hypogonadism types
Primary = gonadal defect
- high FSH and LH
- hypergonadotrophic
Secondary = pituitary, hypothalamus
- low FSH and LH
- hypogonadotrophic - low GnRH
Presentation of hypogonadism in female
Prepubertal
- delayed puberty (after 13 yrs)
Reproductive
- amenorrhea (primary = haven’t began menses by 15 or secondary = miss 3 cycles in a row)
- infertility
- decreased libido
- osteoporosis
- hot flushes
Perimenopausal, menopause (senescent ovaries stop producing oestrogen)
Presentation of hypogonadism in male
Prepubertal
- delayed puberty (after 14 yrs)
Reproductive
- infertility
- decrease libido
- erectile dysfunctions
- osteoporosis
- decreased bear and body hair, breast enlargement, and muscle loss
- 1-2% decline in plasma testosterone per year after 30
Late onset hypogonadism (andropause)
Eunuchoidal proportions
Bone age delayed due to insufficient sex steroids –> delayed epiphyseal closure
==> long bones grow longer than they should leading to disproportionate arms and legs (arm span longer>height)
If an adults has hypogonadism with arm span = height –> defect after puberty
Hypergonadotrophic hypogonadism causes and examples
Male e.g. klinefelter syndrome (47,XXY), late onset male hypogonadism, anorchia or cryptochidism, androgen resistance
Female e.g. Turner syndrome (45,X), menopause
- gonadal dysgenesis/agenesis
- Gonadal diseases e.g. autoimmune, infection, irradiation, chemotherapy
- Steroidogenic enzyme deficiencies e.g. 17 alpha hydroxylase, 17,20 lyase, 20,22 desmolase, 17 beta HSD, 3 beta HSD
- haemochromatosis
Klinefelter Syndrome manifestations
47, XXY
1/1000 males - MC cause of hypoGn and infertility in men
–> small testes
–> poorly developed secondary sexual characteristics
–> tall with eunuchoidal proportions
–> learning disabilities
+/- gynaecomastia (risk of CA breast as for normal females)
+/- 50% have metabolic syndrome
Turner Syndrome
45,X
1/3000 females - MC cause of primary amenorrhea in girls
- -> short stature
- -> cubitus valgus
- -> webbed neck
- -> gonadal dysgenesis (no puberty, infertile)
- -> congenital heart (coarctation)
- -> kidney abnormalities
- -> hypothyroidism and DM
- -> normal intelligence
