The Gonads 2

Question 1

Testosterone can be used two make 2 other hormes- what are they?

Answer 1

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

Question 2

Reduction of testosterone only happens in certain tissues- which tissues are they?

(i.e. which tissues produce DHT)

Answer 2

• Prostate
• Testes
• Seminiferous tubules
• Seminal valves
• Skin
• Brain
• Adenohypophysis

Question 3

Where does aromatisation of testosterone occur?

Answer 3

• Adrenals
• Testes (sertoli cells)
• Liver
• Skin
• Brain

Question 4

How are testosterone and DHT transported?

Answer 4

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

Question 5

Androgen action on foetus

Answer 5

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.

Question 6

Androgen action on adult

Answer 6

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)

Question 7

Define oestrogen

Answer 7

Any substance (natural or synthetic) which induces mitosis in the endometrium.

Question 8

What are some examples of oestrogens

Answer 8

17ß-oestradiol (the main one in women)

Oesterone (precursor)

Oestriol (main oestrogen produced in pregnancy)

Question 9

What are the reproductive effects of oestrogen?

Answer 9

• 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)

Question 10

What are the other effects of oestrogen

Answer 10

• 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

Question 11

What is a progestogen?

Answer 11

Any substance (natural or synthetic) inducing secretory changes in the endometrium

Question 12

Give some examples of some progestogens

Answer 12

Progesterone

17alpha-hydroxyprogesterone

Question 13

Name the effects of progestogens

Answer 13

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

Question 14

Describe the Hypothalamo-pituitary-testicular axis

Answer 14

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.

Question 15

Describe the hypothalamo-pituitary-ovarian axis

Answer 15

The same as the testis one

Hypothalamus produces gnRH pulsatiles

Anterior pituitary gland produces LH and FSH which both stimulate the ovaries

Question 16

What is the early follicular phase?

Answer 16

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.

Question 17

What is the early-mid follicular phase?

Answer 17

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.

Question 18

What is behind the snowball effect of granulosa cells and oestrogen?

Answer 18

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.

Question 19

What is the mid follicular phase?

Answer 19

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

Question 20

What is the late follicular phase?

Answer 20

High oestrogen in the abscence of progesterone for long enough to induce an LH surge.

LH negative feedback means you get lesser FSH surge

Question 21

Negative feedback effects involving oestradiol and inhibin

Answer 21

Inhibin acts on FSH and inhibits it. LH continues to stimulate production of androgens.

Selective negative feedback for FSH only

Question 22

Describe the luteal phase

Answer 22

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

Question 23

Negative feedback effects of oestrogen and progesterone

Answer 23

Question 24

What does amenorrhoea mean?

Answer 24

abscence of menstrual cycles

primary if woman has never had a menstrual cycle

secondary-if woman has had periods which have stopped

Question 25

What does oligomenorrhoea mean?

Answer 25

Infrequent menstrual cycles

various causes but can be due to abscence of LH surge

Question 26

What is infertility?

Answer 26

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)