The Gonads 2

Question 1

What is the key difference between the androgens produced in the gonads and the adrenals

Answer 1

Androgens are produced in both the gonads and the adrenal glands but androstenedione (precursor to testosterone produced in the adrenals) is a much weaker androgen than testosterone.

Question 2

Where and how is testosterone converted into dihydrotestosterone

Answer 2

Prostate
testes 
(seminiferous tubules)
seminal vesicles
skin
brain
adenohypophysis
Reduction (5a-reductase) to dihydrotestosterone (DHT (a more potent androgen)

Question 3

Where and how is testosterone converted into oestrogen

Answer 3

Adrenals
testes (Sertoli cells)
liver
skin
brain
Aromatisation (aromatase) to oestogens eg:
17b-oestradiol, E2

Question 4

What is dihydrotestosterone responsible for

Answer 4

The more potent effects of testosterone, such as baldness, it is essential in males

Question 5

Explain how testosterone can act as a functional hormone and a pro-hormone

Answer 5

▪ Testosterone can act as a precursor which can follow two different reactions to produce other hormones. ▪ Testosterone can act as a functional hormone AND a pro-hormone. ▪ DHT – is far more potent than testosterone and works on the same receptors. ▪ DHT will be produced in target tissues with the 5a-reductase enzyme.

Question 6

How are testosterone and DHT transported in seminiferous fluid

Answer 6

In the seminiferous fluid (in the testes), the testosterone binds to ABG. Androgen binding globulin/protein.

Question 7

How are testosterone and DHT transported in the blood

Answer 7

▪ Main transport is in the BLOOD. ▪ The specific binding protein is SHBG – Sex Hormone Binding Globulin. ▪ Remember that plasma protein binding is in a dynamic equilibrium.
SHBG-60%
Albumin- 38%
Free- 2% (bioactive)

Question 8

Describe the principle actions of testosterone and dihydrotestosterone in the fetus

Answer 8

▪ Development of male internal/external genitalia. ▪ General growth (combined with other hormones). ▪ Behavioral effects (Androgens → oestrogens that affect brain- future and early male neuronal connections- male behaviour).

Question 9

Describe the principle actions of testosterone and DHT in adults

Answer 9

▪ Spermatogenesis. ▪ Growth and development of: o Male genitalia. o Secondary (accessory) sex glands. o Secondary sex characteristics (facial hair). ▪ Stimulate protein synthesis (build muscle – aids growth). ▪ Pubertal growth spurt (with growth hormone – GH). ▪ Feedback regulation. Protein and bone anabolism. Stimulation of sebaceous secretions, development of male behaviours, stimulation of haematoprotein synthesis.

Question 10

What is a consequence of a lack of testosterone in utero

Answer 10

Disrupted development of the testes in utero.

Question 11

How is testosterone produced in utero

Answer 11

Placenta makes hCG, which has the same action of LH, stimulates the testes to make testosterone– testosterone development.

Question 12

What is meant by an oestrogen

Answer 12

Any substance (natural or synthetic) which induces mitosis in the endometrium (e.g. 17b-oestradiol – main hormone in menstrual cycle, Oestrone – precursor, Oestriol – main hormone of pregnancy). ▪ Produced from androstenedione and testosterone.

Question 13

What are the three androgens from which oestrogens are derived from

Answer 13

Testosterone
Androstenediol
Androstenedione

Question 14

Describe the effects of oestrogens on the reproductive system

Answer 14

ENDOMETRIUM: Stimulates proliferation (mitosis) i.e. womb thickening
MENSTURAL CYCLE: Triggers LH surge resulting in ovulation
VAGINA / CERVIX: secretions
BREASTS: Stimulates growth of ductile system
SKIN: Decreases sebaceous gland secretion

Question 15

Describe some of the other effects of oestrogens

Answer 15

Feedback regulation on GnRH (negative and positive)
stimulates osteoblasts
Metabolic actions (e.g. on lipids)
Behavioural effects
Increases salt (and water) reabsorption
Increases plasma protein synthesis (hepatic effect)
Influences the release of other hormones (e.g. prolactin, thyrotrophin)

Question 16

Describe the effects of oestrogens in lipids

Answer 16

increases HDL levels → stops at menopause → CVS problems

Question 17

Why are females more susceptible to osteoporosis after menopause

Answer 17

Oestrogens stimulate osteoblast growth

Hence after the menopause, when oestrogen production decreases, bone loss.

Question 18

Explain how oestrogen may increase salt and water reabsorption

Answer 18

Oestrogens stimulate hepatic protein synthesis, including angiotensinogen 2, an early precursor to angiotensin 2. This stimulates salt reabsorption directly and indirectly (stimulates aldosterone)

Question 19

What is meant by a progestogen

Answer 19

Definition:
Any substance (natural or synthetic) inducing secretory changes in the endometrium progesterone
17a-hydroxyprogesterone

Question 20

What are some of the effects of progestogens

Answer 20

Negative feedback regulation on hypothalamic GnRH

Increase in basal body temperature
Decreases renal NaCl re-absorption (competitive inhibition of aldosterone
Stimulates growth of alveolar system in breast

Question 21

Describe the release of LH and FSH

Answer 21

Pulses of LH and FSH are coincident with pules of GnRH

Question 22

Describe the hypothalamo-pituitary-testicular axis

Answer 22

1. Hypothalamus secretes Gonadotrophin Releasing Hormone – GnRH (pulsatile activity). 2. GnRH passes down to the gonadotrophs in the adenohypophysis which produces LH and FSH. 3. LH targets Leydig cells, FSH targets Sertoli cells. 4. FSH stimulates Sertoli cells to produce inhibin while LH stimulates Leydig cells to produce androgens (main hormone = testosterone). 5. Testosterone has virilisation effects and a direct/indirect effect on the axis. 6. This –ve feedback decreases amplitude of pulses of GnRH. 7. Main effect of –ve feedback by testosterone is on LH production. 8. (Inhibin has a similar effect on the FSH axis).

Question 23

What is meant by virilisation

Answer 23

the development of male physical characteristics (such as muscle bulk, body hair, and deep voice) in a female or precociously in a boy, typically as a result of excess androgen production.

Question 24

What cannot occur without the correct functioning of Sertoli cells

Answer 24

Spermatogenesis.

Question 25

How do LH and FSH work

Answer 25

Synergistically

Question 26

Summarise the endocrine control of testicular function

Answer 26

1. Androgen production (Leydig cells)
stimulated by LH
reduced by testosterone 
negative feedback to reduce LH and GnRH
i. Direct – Pituitary – Reduce LH release. ii. Indirect – Hypothalamus – Slows the GnRH pulse generator.

2. Spermatogenesis (Sertoli cells)
   stimulated by FSH
   i. Also requires GnRH/LH/testosterone system to complete.
   limited by inhibin negative feedback (direct and indirect)
   Sperm maturation also requires testosterone

Question 27

Describe what happens in the early-follicular phase

Answer 27

▪ Oestrogen and progesterone levels are low so there is little –ve feedback → increase in production of LH, FSH and GnRH. ▪ LH and FSH stimulate development of some follicles in the ovaries. ▪ There is a little rise in 17a-hydroxyprogesterone during ovulation

Question 28

Describe what happens in the early mid-follicular phase

Answer 28

▪ There is no further increase in FSH or LH. ▪ Oestrogen levels are beginning to rise dramatically (increases in the blood and in the ovaries)- increases as follicles get bigger ▪ Progesterone does NOT change.

Question 29

Describe the local positive feedback loop in developing follicles

Answer 29

Ovaries – Local positive feedback loop in developing follicles enhances oestradiol production. ▪ Thecal cell = LH Receptor. ▪ Granulosa cell = FSH Receptor.

1. Thecal cells respond to increase in LH by increasing androgen production. 2. FSH binds to FSH receptors on Granulosa cells which activates aromatase = androgens → 17b-oestradiol. 3. An auto-positive feedback loop is initiated – oestrogens produced by Granulosa cells have an cryptocrine (an effect inside the cell itself) effect and stimulate aromatase via a secondary messenger system and cell proliferation to create more Granulosa cells. 4. Causes 17b-oestradiol to increase at an increasing rate by creating more aromatase and creating more cells.
   Rising plasma E2&raquo_space;> granulosa cell growth

More granulosa cells&raquo_space;» more E2 synthesis

Question 30

Describe what happens in the mid-follicular phase

Answer 30

▪ Rising oestrogen levels negatively feedback on FSH. ▪ Selective negative feedback loop by oestrogen and inhibin on the GnRH-FSH system results in atresia of all follicles that are FSH dependant → Graafian follicle survives. ▪ A lot of the follicles are FSH dependant so by removing FSH, the follicles begin to undergo atresia. ▪ LH is still produced to stimulate production of androgens but FSH is inhibited.

Question 31

Describe the Graafian follicle

Answer 31

▪ Largest follicle – no longer needs FSH to develop. ▪ Produces largest amount of 17b-oestradiol. ▪ Rising concentration of 17b-oestradiol in absence of progesterone, for a minimum of 36 hours and at a sufficient level triggers –ve feedback switching to +ve feedback, causing the LH surge.

Question 32

Describe how oestrogen can have positive and negative feedback effect on the hypothalamus and pituitary

Answer 32

Two populations of nuclei in the hypothalamus that respond to oestrogen, one is positively fedback, the other, negatively feedback.

Concentrations 10x higher than normal required to activate positive nuclei.

Question 33

Describe the late follicular phase

Answer 33

▪ High oestrogen in the absence of progesterone for long enough to induce the LH surge. ▪ LH surge is sufficiently high to overcome the FSH –ve feedback so you get a lesser FSH surge.

Question 34

Describe the luteal phase

Answer 34

If fertilisation does not occur, progesterone, oestradiol and inhibin exert a negative feedback on LH and FSH release →
luteolysis and menstruation.
1. Post-ovulation, follicle collapses to a corpus luteum. 2. Initially, FSH and LH still released → corpus luteum stimulated to produce more oestrogen and progesterone.
3. Oestrogen and progesterone → reduce levels of LH and FSH (mainly from progesterone which limits the oestrogen from inducing a positive feedback event).
4. As LH and FSH fall, corpus luteum no longer creates oestrogen and progesterone → LH and FSH begin to rise. If fertilisation occurs, a molecule that mimics LH is created called Human Chorionic Gonadotrophin (hCG).

Question 35

Describe Amenorrhea

Answer 35

Absence of menstrual cycles. Primary – Menstrual cycles NEVER happened to begin with. Secondary – Menstrual cycles did happen but the stopped (e.g. pregnancy is a physiological cause).

Question 36

Describe oligomenorrhea

Answer 36

Infrequent menstrual cycles. Causes are various but can be due to an absence of LH surge (e.g. due to insufficient oestrogenic effect at the end of the follicular phase).

Question 37

Define infertility

Answer 37

Couple cannot get pregnant following 12 months of regular unprotected sex

Question 38

What are some of the causes of infertility

Answer 38

Pituitary failure- no FSH or LH to simulate sperm production
Prolactinoma- prolactin inhibits FSH and LH
Testicular failure e.g. mumps, Klinefelter syndrome (XXY)
Ovarian failure e.g. Turner syndrome (XO)
Polycystic ovarian syndrome (PCOS)

Question 39

What can PCOS cause

Answer 39

Infrequent periods
Hyper-androgenaemia e.g. increased male pattern hair, acne
Polycystic ovaries (increased number of enlarging ovarian follicles)