11- Gonads 2

Question 1

Describe how testosterone can act as a precursor for 2 hormones

Answer 1

testosterone can be reduced to form DIHYDROTESTOSTERONE (DHT) which is far more potent but will still work on the SAME androgen receptors
• DHT will be produced in target tissue that has the 5α-reductase enzyme
• Testosterone can act as a precursor in the production of oestrogen (it is
produced in tiny amounts in the female adrenals)
• Aromatisation - testosterone can be aromatised to form OESTROGENS

Question 2

How is testosterone transported in the blood and seminiferous fluid, give %

Answer 2

SEX HORMONE BINDING GLOBULIN 60%
Albumin 38%
Free 2%

In seminiferous fluid: ANDROGEN BINDING GLOBULIN (ABG)

Question 3

What impact to androgens have on foetuses

Answer 3

• Development of male internal and external genitalia
• Stimulate general growth (male babies tend to be larger than female babies due to the effects of androgens in the foetus)
• Behavioural effect associated with androgens
• Androgens can be converted to oestrogens which bind to oestrogen receptors
• Some behavioural effects may be due to oestrogen having an effect on the oestrogen receptors in the brain

Question 4

What impact do androgens have on adults

Answer 4

Spermatogenesis
• Growth and development of:
Male genitalia
Secondary (accessory) sex glands Secondary sex characteristics
• Stimulation of protein synthesis
• Pubertal growth spurt (with Growth Hormone)
• Behavioural (CNS) effects
• Feedback regulation

Question 5

What is the definition of oestrogen.
What is the main oestrogen in the menstrual cycle
What is the precursor
What is the main oestrogen in pregnancy

Answer 5

DEFINITION: any substance (natural or synthetic) that induces mitosis in the endometrium
• 17b-oestradiol is the MAIN hormone produced in the menstrual cycle
• Oestrone is a precursor
• Oestriol is the main oestrogen produced in pregnancy

Question 6

Describe the principle actions of oestrogen

Answer 6

Stimulate proliferation (mitosis) of the endometrium
• Final maturation of the follicle during the follicular phase of the menstrual cycle
• Induction of LH surge resulting in ovulation
• Effects on vagina and cervix
• Stimulates growth of ductile system of breast
• Decreases sebaceous gland secretion (NOTE: androgens stimulate sebaceous gland secretion)
• Increased salt and water reabsorption
• Increased plasma protein synthesis (hepatic effect)
• Metabolic actions (e.g. on lipids)
Tend to increase HDL levels
Menopause - oestrogen levels are low so carbohydrate and lipid metabolism will be affected - women will become more susceptible to cardiovascular problems
• Stimulates osteoblasts (androgens also do this)
• Influences the release of other hormones (e.g. prolactin, thyrotrophin)
• Behavioural effects
• Feedback regulation (negative and positive)

Question 7

What is a progestogen and give 2 examples

Answer 7

DEFINITION: any substance (natural or synthetic) which induces secretory changes in the endometrium
• EXAMPLES:
Progesterone
17α -hydroxyprogesterone

Question 8

Describe the principle action of progestogens

Answer 8

Stimulates secretory activity in endometrium and cervix
The secretions are different in character - they are thick and viscous so are less easily penetrated by spermatozoa than the oestrogen induced watery secretions
• Stimulates the growth of alveolar system in the BREAST
• Decrease renal NaCl reabsorption - due to competitive inhibition of
aldosterone
• Associated with an increase in body temperature (because progesterone is released in large amounts)
• Negative feedback regulation

Question 9

Describe the Hypothalamo-Pituitary-Testicular Axis

Answer 9

Neurones in the hypothalamus produce Gonadotrophin Releasing Hormone (GnRH)
• GnRH passes down to the gonadotrophs in the adenohypophysis which produce LH and FSH
• LH and FSH work on the testes
• FSH stimulates the Sertoli cells to produce INHIBIN
• In between seminiferous tubules you find Leydig Cells which have LH receptors - produce androgens (testosterone is the main precursor androgen produced)
• Testosterone has virilisation effects (development of male physical characteristics)
• Testosterone also has direct (to the pituitary) and indirect (to the hypothalamus) effects on the hypothalamo-pituitary axis
• This negative feedback decreases the amplitude of the pulses of GnRH
• The MAIN effect of negative feedback by testosterone is on LH production (LH diminishes due to negative feedback by testosterone)
• INHIBIN has a similar effect on the FSH axis

Question 10

Describe androgen control of leydig cells

Answer 10

Androgen Production = LEYDIG CELLS
Stimulated by GnRH - specifically by LH Reduced by negative feedback by testosterone
• Direct - Pituitary - reduce LH release
• Indirect - Hypothalamus - slow the hypothalamic GnRH pulse
generator

Question 11

Describe androgen control of Sertoli cells

Answer 11

Spermatogenesis = SERTOLI CELLS
Stimulated by GnRH - specifically by FSH
Also requires GnRh/LH/Testosterone system for complete spermatogenesis
Limited by Inhibin negative feedback (direct and indirect)

Question 12

Describe the Hypothalamo-Pituitary-Ovarian Axis

Answer 12

Hypothalamus generates pulses of GnRH
Which stimulate production of LH and FSH in the pituitary
These have effects on the ovary

Question 13

Describe the early follicular phase of the menstrual cycle (days 1-4)

Answer 13

• Oestrogen and progesterone levels are low so there is little negative feedback
so there is an increase in the production of LH and FSH and GnRH
• LH and FSH start stimulating the development of some follicles in the ovaries
• There is a little rise in 17a-hydroxyprogesterone during ovulation

Question 14

Describe the early mid follicular phase (days 4-7)

Answer 14

• There is no further increase in FSH or LH
• Oestrogen levels are beginning to rise dramatically (increases in the blood and
in the ovaries)
• Progesterone does NOT change

Question 15

Describe how Local positive feedback loop in developing ovarian follicles enhances oestradiol production

Answer 15

Thecal cells respond to LH by increasing androgen production
• FSH binds to the FSH receptors on the Granulosa cells which activates
AROMATASE
• Aromatase converts androgens (from thecal cells) to 17β-oestradiol
• At the beginning, FSH and LH levels are high causing a rise in oestrogen levels
• Oestrogens produced by the granulosa cells will bind to the oestrogen
receptor on the same granulosa cell and stimulate the aromatase enzyme via a second messenger system = AUTO-POSITIVE FEEDBACK
• This means that the more oestrogen is produced by androgens, the more oestrogen is produced overall due to the positive feedback
Granulosa cells multiply and get bigger
• This means there is more oestrogen so plasma oestrogen levels RISE

Question 16

Describe the mid follicular phase: days 6-10

Answer 16

At this point the rising oestrogen levels have a negative feedback effect on FSH
• Within the follicles, there are developing ova which are at different stages of development
• A lot of these follicles are FSH dependent so by removing FSH, you kill the cells which are still FSH dependent (ATRESIA)
• There is usually only ONE OVUM which can grow under its own production of local oestrogens and this is the GRAAFIAN FOLLICLE

Question 17

How does the Graafian follicle survive, but the others don’t

Answer 17

Selective negative feedback loop by oestrogen and inhibin on the GnRH-FSH system results in ATRESIA (regression) of all follicles that are still FSH dependent: GRAAFIAN follicle survives

Question 18

Describe how the Graafian follicle causes the LH surge

Answer 18

The LARGEST follicle - it no longer needs FSH to develop and proliferate
• It continues to grow and produce large amount of 17b-oestradiol
• The rising concentration of 17b-oestradiol in the absence of progesterone, for
a minimum of 36 hours and at a sufficient level, results in the negative feedback switching to positive feedback which causes the LH SURGE

Question 19

Describe the late follicular phase 10-14

Answer 19

At this stage we have had high oestrogen in the absence of progesterone for long enough to induce an LH surge
• The LH surge at this point is sufficiently high to overcome the FSH negative feedback and so you get a lesser FSH surge

Question 20

Describe the luteal phase

Answer 20

After ovulation, the cells of the follicle collapse to form a corpus luteum
• The corpus luteum has cells which still have FSH and LH Receptors
• As oestrogen and progesterone levels fall after ovulation, there is initially FSH and LH being released
• This stimulates the corpus luteum to produce more oestrogen and
progesterone
• Oestrogen and progesterone levels will increase which exerts a negative feedback effect on the hypothalamo-pituitary axis

Question 21

What happens to the hormones if fertilisation doesn’t occur

Answer 21

If fertilisation does NOT occur - PROGESTERONE, OESTRADIOL and INHIBIN exert a negative feedback on LH and FSH release - leading to LUTEOLYSIS and MENSTRUATION

Question 22

What is amenorrhoea and Oligomenorrhoea

Answer 22

Amenorrhoea
DEFINITION = absence of menstrual cycles
• PRIMARY = menstrual cycles NEVER happened
• SECONDARY = menstrual cycles did happen but then stopped (can be
physiological e.g. pregnancy)

Oligomenorrhoea
DEFINITION = infrequent menstrual cycles
• Causes: various, but can be due to absence of LH surge (e.g. due to insufficient
oestrogenic effect at the end of the follicular phase

Question 23

What happens if fertilisation occurs

Answer 23

If fertilisation occurs, you will need a lot of oestrogen and progesterone so the
placenta, at an early stage, will start producing a molecule which mimics the effects of LH - Human Chorionic Gonadotrophin (hCG)

Question 24

Just prior to ovulation the circulating concentration of FSH increases [a]
During the luteal phase the circulating LH concentration reaches its peak [b]
Secondary amenorrhoea is a normal physiological response to pregnancy [c]
Chronic high circulating prolactin concentrations are associated with a loss of libido [d]
The basal body temperature decreases at ovulation [e]

Answer 24

T f t t f

Question 25

During the menstrual cycle the principal oestrogen produced is oestriol [a]
There is an increase in the blood progesterone concentration during the early follicular phase [b]
Both progesterone and oestradiol are released in the luteal phase [c]
Ovulation is induced by a large increase in circulating progesterone concentration [d]
The central (mid) event of the menstrual cycle is ovulation [e]

Answer 25

F f t f t