The Gonads 2 Flashcards
Testosterone can be used two make 2 other hormes- what are they?
Testosterone is a precursor that can:
1) Be reduced by 5alpha- reductase to form dihydrotestosterone which is a more stronger and more potent androgen than testosterone. Dihydrotestosterones can will still work on the androgen receptors.
2) Aromatisation by aromatase enzymes to for oestrogens
Reduction of testosterone only happens in certain tissues- which tissues are they?
(i.e. which tissues produce DHT)
- Prostate
- Testes
- Seminiferous tubules
- Seminal valves
- Skin
- Brain
- Adenohypophysis
Where does aromatisation of testosterone occur?
- Adrenals
- Testes (sertoli cells)
- Liver
- Skin
- Brain
How are testosterone and DHT transported?
Mainly in the blood, attached to sex hormone binding globulin (SHGB)
They also attach to albumin which are non-specifc binding protiens. Remember that plasma protein binding is in dynamic equilibrium.
Testosterone can also be found in seminiferoud fluid and here, it is bound to androgen binding protein (ABP)
Around 2% of the hormones are in the free pool and are bioactive
Androgen action on foetus
Development of male internal and external genitalia
Fetal growth (acting with other hormones)- male babies tend to be bigger than female ones.
Behavioural effect associated with androgens.
Androgen action on adult
needed for spermatogenesis
Also needed for the growth and development of male genitalia and secondary sex characteristics like hairy face. Secondary sex characteristics too.
Needed for protein and growth anabolism (muscle and bone growth)-stimulation of protein synthesis.
Behavioural: male sexual behaviour
Pubertal growth spurt (GH)
Define oestrogen
Any substance (natural or synthetic) which induces mitosis in the endometrium.
What are some examples of oestrogens
17ß-oestradiol (the main one in women)
Oesterone (precursor)
Oestriol (main oestrogen produced in pregnancy)
What are the reproductive effects of oestrogen?
- Endometrium- stimulates proliferation- i.e. womb thickening
- Final maturation of the follicle during follicular phase of menstrual cycle.
- Menstrual cycle- tirggers LH surge resulting in ovulation
- increase secretions in vagina and cervix
- Stimulate growth of suctile system in breasts
- decrease sebaceous gland secretion in breast (n.b androgen increase sebaceous gland secretion)
What are the other effects of oestrogen
- Negative and positive feedback regulation (on GnRH)
- Stimulates osteoblasts (androgens also do this)
- Metabolic actions: tend to increase HDL levels. Menopause- oestrogen levels are low so carbs and lipid metabolism will be affected and women will become more susceptible to cardiovascular problems
- Behavioural effects
- Increase in salt and water reabsorption
- Increase plasma protein synthesis (hepatic effect)
- Influence the release of other hormones like prolactin
What is a progestogen?
Any substance (natural or synthetic) inducing secretory changes in the endometrium
Give some examples of some progestogens
Progesterone
17alpha-hydroxyprogesterone
Name the effects of progestogens
Stimulates secretory activity in endometrium and cervix.
Secretions are thick and viscous so are less easily penetrated by the spermatozoa than the oestrogen induced watery secretions.
Negative feedback regulation on hypothalamic GnRH
Stimulates growth of alveolar system in the breast
Decreases renal NaCl reabsorption (competitive inhibition of aldosterone)
Associated with an increase in body temperature when released in large amounts- just after ovulation
Describe the Hypothalamo-pituitary-testicular axis
Neurones in the hypothalamus produce Gonadotrophin Releasing hormone (GnRH)
The activity of GnRH release is pulsatile- generated by the hypothalamus
GnRH passes down to the adenohypophysis and binds to the gonadotrophs there. This stimulates production and release of LH and FSH which both work on the testes
LH binds to the Leydig cells and testosterone is produced
FSH binds to Sertoli cells, stimulating it to produce inhibin
Both the testosterone and the inhibin produced have direct and indirect effects on the axis. The pulsatile frequency will drop. Testosterone production can also reduce LH production and likewise, inhibin can inhibit FSH production.
Describe the hypothalamo-pituitary-ovarian axis
The same as the testis one
Hypothalamus produces gnRH pulsatiles
Anterior pituitary gland produces LH and FSH which both stimulate the ovaries
What is the early follicular phase?
It is the first day of menstrual bleeding in day 1.
Oestrogen and progesterone levels are low so there is little negative feedback and therefore there is a rise in LH, FSH and GnRH.
LH and FSH start stimulating development of follicles in the ovaries. Developing follicles, 5-10 eggs will enlarge and grow. Eventually only one will be dominant.
They are growing under the regulation of FSH. They start producing oestrodiol. Because the follicles are small, they do not have a lot of oestrodiol.
What is the early-mid follicular phase?
There is no further increase in FSH or LH
Oestrogen levels rise dramatically as there is now one dominating follicle making lots or oestrogen. The oestrogen being produced stimulates the granulosa cells to grow more so more oestrogen is produced- snow ball effect. Oestrogen negative feedback stops LH and FSH from being produced.
Progesterone does not change.
What is behind the snowball effect of granulosa cells and oestrogen?
Thecal cell= LH receptor- important for androgen production
Granulosa cell= FSH receptor. When binding occurs, aromatse is activated.
Aromatase converts the androgens produced to 17ß-oestradiol
Oestrogen produced by granulosa cells will bind to the oestrogen receptor on the same granulosa cell and stimulate aromatase enzyme via a second messenger system= AUTO POSITIVE FEEDBACK (granulosa cells actually increase in size)
Lots and lots of oestrogen is produced.
What is the mid follicular phase?
Rising oestrogen falling FSH. Within the follicles, there are developing ova at different stages of development- a lot of them are FSH dependent, so removing the FSH will kill cells that are FSH dependent.
There is usually 1 ovum that grows under its own production of local oestrogens- this is the graafian follicle
What is the late follicular phase?
High oestrogen in the abscence of progesterone for long enough to induce an LH surge.
LH negative feedback means you get lesser FSH surge
Negative feedback effects involving oestradiol and inhibin
Inhibin acts on FSH and inhibits it. LH continues to stimulate production of androgens.
Selective negative feedback for FSH only
Describe the luteal phase
Corpus luteum form after follicle collapse. The corpus luteum has cells wich have FSH and LH receptors.
Oestrogen and progesterone levels fall after ovulation and there is initially FSH and LH being released. Therefore there is stimulation for more oestrogen and progesterone.
High levels of progesterone swamps any chance of positive feedback inorder to produce more oestrogen.
Unless the FSH and LH levels are restored, there cannot be any more oestrogen and progesterone. Levels fall.
This causes reduced negative feedback and the LH and FSH will start to ricse again. If fertilisation occurs, there needs to be a lot of oestrogne and progesterone so hCG is formed as it mimics LH
Negative feedback effects of oestrogen and progesterone
What does amenorrhoea mean?
abscence of menstrual cycles
primary if woman has never had a menstrual cycle
secondary-if woman has had periods which have stopped
What does oligomenorrhoea mean?
Infrequent menstrual cycles
various causes but can be due to abscence of LH surge
What is infertility?
inability to get pregnant/ impregnate
various causes:
- Pituitary failure
- Prolactinoma
- Testicular failure e.g. mumps, Klinefelter syndrome (XXY)
- Ovarian failure e.g. Turner syndrome (XO)
- Polycystic ovarian syndrome (PCOS)
Infrequent periods
Hyper-androgenaemia e.g. increased male pattern hair, acne
Polycystic ovaries (increased number of enlarging ovarian follicles)
