3-Mnu - Week 2

Front 1

What do Leydig cells do? What controls their function

Back 1

LH causes Leydig cells to secrete testosterone.

Front 2

What is capacitation?

If you have 20-40 100mil sperm /mL what happens to your fertility?

Back 2

A reaction of sperm in the female reproductive tract - allows them to swim faster.

- if 20 - 400 mil sperm / mL then fertility down by 50%. If less than 20 you are INFERTILE

Front 3

*pulsatile release of GnRH causes the release of which 2 hormones from the ant. pituitary (in men)? What are the effects of these hormones?

Which 2 hormones provide negative feedback control?

Back 3

GnRH causes the release of:
FSH -- stimulates (via 2nd msgnr) the sertoli cells to secrete inhibin (neg feedback to FSH) and ABP which binds testosterone
LH -- stimulates the Leydig cells to secrete testosterone (acts on sertoli cells, binds ABP and some is released to the the circulation)
Inhibin (from sertoli cells) neg fback of FSH
Testosterone (from leydig cells) neg feedback on LH and GnRH

Front 4

Why is the concentration of testosterone so much higher in the testes?

Back 4

B/c the sertoli cells secrete Androgen Binding protein and this mops up all the testosterone and keeps in within the testes. Testosterone is a steroid hormone, so if there was no ABP then it would freely diffuse away.

Front 5

Where is testosterone produced and by what enzyme?

What are the 2 enzymes that will act on testosterone and what (respectively) can they convert it into? Where in the body does this occur?

Back 5

17B - hydroxysteroid dehydrogenase will convert DHEA & Androstenedione into testosterone ** in the testes***

Testosterone can be converted to:
- Dihydrotestosterone, by 5a-Reductase
or,
- Estradiol by CYP19 Aromatase
** in the peripheral tissue **

Front 6

What hormones do the following plasma proteins bind?
- CBG
- GBG
- Albumin

Back 6

CBG will bind:
- Progesterone (18%) and Cortisol (90%)

GBG will bind:
- Testosterone (65%), Estradiol (38%), and Androstenedione (8%)

Albumin will bind:
Androsternedione (85%), Progesterone (80%), Estradiol (60%) and a wee bit of Cortisol (6%)

Front 7

Where would you find the 2 types of 5a-Reductase?

What can be used to inhibit 5a-Reductase?

Back 7

Type 1: skin, body, scalp
Type 2: Genital skin / tissues & prostate
** Type 2 will cause enlargement of the prostate

Finasteride will inhibit 5a-Reductase (specific antagonist)

Front 8

When testosterone enters a cell it has 2 possible actions. The first is to bind a cytoplasmic receptor and act as a TF. What are the 5 effects that it will have?

What is the other option for the testosterone and what 2 effects will this have on the body?

Back 8

testosterone + receptor =
1. Muscle mass &sex drive
2. Sexual differentiation
3. Spermatogenesis
4. Wolffian stimulation
5. Gonadotropin regulation

If not, 5a-Reductase will convert testosterone into dihydrotestosterone and this will bind much more tightly to the receptor --> Nucleus --> TF causing:
- External virillization
- Sexual maturation at puberty

Front 9

What are the 2 functions of testosterone before birth?

What does it do in the sex-specific tissues?

In addition to secondary sexual Xtics (laryng, hair, muscles, & sebacious glands), what are 3 non-reproductive functions of testosterone?

Back 9

-Make the reproductive tract & external genitalia male, and cause the decent of the testes.

- Maintains reprod tract at puberty and thru adulthood. Promotes spermatogenesis and the development of the prostate and sem vesicles.

- promotes protein synthesis
- stimulates bone growth
- activates aggression and sexual behaviour

Front 10

What happened when they gave primates a constant dose of GnRH?

What would happen if systemic injection of testosterone were given?

Back 10

The GnRH receptors got down-regulated and this resulted in the less of a pituitary response (lower levels of FSH & LH)

- Peripheral [testosterone] will increase and this will cause a negative feedback to the GnRH, FSH and LH, causing a decrease in the [testosterone] in the testes = poor reproductive function and possible infertility

Front 11

What happens in the ovary at day 6 of the cycle?

Where does most of the estrogen come from?

Back 11

Only one of the follicles develops an antrum --> becomes dominant and secretes estrogen. Other follicles will become apoptotic and regress.

Most estrogen comes from the follicular cells and only a small amount come from the theca.

Front 12

What hormone will cause multiple follicles to enter the antrum stage?

What will FSH & Est cause?
LH & FSH?
LH?

Back 12

FSH will cause multiple follicles to develop antrums. Can be given for in-vitro harvesting.

FSH & Est -- granulosa proliferation
LH & FSH -- estrogen production
LH -- development and maintenance of CL, Est & Prog secretion

Front 13

What happens when LH binds to it's receptor on thecal cells?

What happens when FSH binds to it's receptor on granulosa cells?

Back 13

LH binds -->cAMP --> PKA = conversion of cholesterol to Androstenedione. A little bit of the andros is converted into estradiol but most diffuses into the the Granulosa cell.
FSH binds --> cAMP --> PKA = stimulated P450 Aromatase to convert andros to estrone --> estradiol (released into the circulation).

Front 14

When is progesterone highest?
When are estradiol and estrone low, high and highest?
Arrange in order of potency: estrond, estradiol, estriol
2% of estradiol is free, 60% is bound to ____ and 38% is bound to _______.

Back 14

midluteal phase
Estradiol and estrone:
low - early follicular
high - midluteal (b/c coming from Corpus)
Highest - preovulatory b/c being secreted by granulosa cells
Estradiol > estrone > estriol

2% of estradiol is free, 60% is bound to albumin and 38% is bound to GBG

Front 15

During the early/mid follicular stage:
- which is higher LH or FSH?
- put these in order from highest to lowest: est, inhibin, prog
- what is providing + feedback, -- feedback?

Back 15

- FSH > LH stimulating the granulosa cells to secrete estrogen
- est, inhibin, progesterone
- estrogen + on granulosa cells (stimulates prolif, causes more est to be made = feed forward)
estrogen -- on FSH, LH and GnRH

Front 16

During the late follicular and ovulation:
- which is higher LH or FSH?
- put these in order from highest to lowest: est, inhibin, prog
- what is providing + feedback, -- feedback?

Back 16

- The LH will rise above FSH and surge causing ovulation. After ovulation the CL will maintain LH levels.
- Estrogen (also surges), inhibin, progesterone
- At high levels estrogen will lose it's inhibitory effects and + Fback to increase # of GnRH receptors and ant. pit. LH. (** will only occur if levels of prog very low) The rising inhibin will - Fback FSH

Front 17

During the early/mid luteal phase:
- which is higher LH or FSH?
- put these in order from highest to lowest: est, inhibin, prog
- what is providing + feedback, -- feedback?

Back 17

- LH > FSH (both steady)
- Prog > Est > inhibin, all have a steady peak then decline
- the corpus luteum will secrete E, P & I and all these will have - Fback to the hypothalm (GnRH) and ant. pituitary FSH/LH.
** progesterone will inhibit LH and these declining levels of LH cause the luteum to regress.

Front 18

During the late luteal phase:
- which is higher LH or FSH?
- put these in order from highest to lowest: est, inhibin, prog
- what is providing + feedback, -- feedback?

Back 18

B/c of low LH --> Corpus Luteum dies.
- The FSH comes back above LH (stimulates new follicles)
- Progesterone falls most and goes back to the bottom, follwed by inhibin then estrogen
- With the death of the CL there is a loss of estrogen and progesteron = loss of negative feedback

Front 19

What is the role of Estrogen? Androgens?

Back 19

Estrogens: 1 and 2dary characteristics (fat distribution and breast development)

Androgens: Pubic/axillary hair and libido

Front 20

What are the steps following the fusion of the sperm and egg membranes?

Back 20

- sperm nucleus moves into the egg.
- the egg completes meiotic division
- egg and sperm nuclei fuse to form the zygote. (the 2nd polar body is cast off)
Zygote develops for ~4days into a blastocyst as it does so it moves down the fallopian tube. Implants at days 5-9.

Front 21

What is the effect of prostaglandins on the endometrium?
What is the decidua?

Back 21

- increase vascularization & cause edema, both of which will facillitate implantation
-Decidua = point at which the embryo implants
** human embryo's use interstitial implantation (go under the uterine lining).

Front 22

A mother and her fetus are genetically distinct. Why doesn't the mother develop an immune response to the fetus?

Back 22

1. The trophoblastic cells of the placenta do NOT contain any MHC I or II = non-antigenic

2. The hormones of pregnancy suppress the maternal immuny system (will need to consider this is she is being treated for an autoimmune disease)

Front 23

How many vessels are in the umbilical cord?
Why don't maternal & fetal blood mix? (ie describe the structures involved)
Where does the placenta come from?

Back 23

There is one vein and 2 arteries

The fetal vessels sit in a pocket of 1-cell thick trophoblastic sacs. These sacs are then sitting in a pool of maternal blood thus the 2 don't mix!
The placenta is of fetal origin.

Front 24

What is the source and function of:
- hCG
- hPL

Back 24

hCG:
-source: blastocyst and early placenta
- function: maintains the CL (need it for E & P)

hPL (human placental lactogen)
- source: placenta
- function: prepares the mammary glands and reduces maternal use of glucose.

Front 25

What is the source and function of the following:
-Estrogen
- Progesterone
- Relaxin

Back 25

Estrogen:
- source: Placenta (& CL)
- function: growth of myometrium, development of mammary glands & fetus

Progesterone:
-source: placenta (& C.Luteum)
-function: inhibits spontaneous contractions and follicular development, helps develop mammary glands

Relaxin: (for pushin!)
- source: Placenta (& CL)
- fucntion: softens cervix, loosens connective tissue of the pelvis = facilitates birth

Front 26

What hormonal source switches at 6 weeks?

Back 26

First 6weeks, the fetus relies on the ovaries (CL) for E & P. After that is relies on the placenta. (therefore can remove the ovaries after 6th week).

Front 27

What hormone peaks at about the 8th week of pregnancy? What is it's function?
There are 3 other hormones of pregnancy, and all of them climb steadily throughout. What are they in order from highest to lowest?

Back 27

hCG -- it maintains the corpus luteum and this keeps E & P levels high.
Progesterone > Estrogen > hPL

Front 28

Placental lactogen is similar in structure to GH & prolactin. What are it's 3 functions? Where are it's levels the highest?
What can it be used as a indicator of?

Back 28

hPL Fucntions:
1. Na/K/Ca+ retention ( Ca is especially needed for fetal skeleton)
2. Decreases maternal glucose use (ie. diverts the glucose to the fetus)
3. Promotes lipolysis

It is high in the mother and low in the fetus

[hPL] is proportional to fetal size

Front 29

Maternal cholesterol diffuses into the placenta where it is converted to ___1___, which the placenta cannot convert to androgens. To get around this, 1 goes to the adrenal cortex to become ___2___, goes to fetal liver to get ______. It then returns to the placenta where it is converted to ____3___ --> maternal blood.
2 can also bypass the liver and go back to the placenta to become what 2 hormones?

Back 29

Maternal cholesterol diffuses into the placenta where it is converted to PROGESTERONE which the placenta cannot convert to androgens. To get around this, PROG goes to the adrenal cortex to become DHEAS, goes to fetal liver to get SULPHINATED (16a-DHEAS). It then returns to the placenta where it is converted to ESTRADIOL--> maternal blood.

(~40%) of the DHEAS will bypass the fetal liver and go back to the placenta to become ESTRADIOL & ESTRONE.

Front 30

What is the effect of sulphinating DHEA?
When is the fetal adrenal cortex at it's largest? When does it convert to a an adult cortex?

Back 30

Sulphur conjugation of DHEA makes it biologically less active (so it won't affect fetal sexual differentiation).
The adrenal cortex is mostly fetal type in the prenatal trimesters. It regresses a lot in the postnatal months and is gone by childhood.

Front 31

What are 5 possible triggers for the initiation of labour?

Describe the feedforward loop of labour?

Back 31

1. increases in E and oxy receptors
2. increased fetal cortisol
3. increased placental Cortisol Releasing hormone
4. Increased prostaglandins
5. Decreased progesterone

When the uterine contracts, the fetal head will engage the cervix and this stimulates CERVIAL MECHANORECEPTORS causing INCREASE OXY and PROSTAGLANDINS which only makes the uterus contract more!

Hint 31

When the uterus contracts, the fetal head will engage the cervix and this stimulates _____, causing _____ and ____ which only makes the uterus contract more!

Front 32

Is milk produced during pregnancy? Why or why not?

What hormone stimultes the myoepithelial cells of the breast?

Back 32

No, b/c E & P will inhibit prolactin; E & P will develop the system but they stop it from acting. Once the placenta is lost, inhibition of prolactin is lost with it and milk can be produced.

Oxytocin!!

Front 33

Describe the pathways (from brain to breast) that results in:
- milk production.
- Milk ejection

Back 33

(* dopamine will travel to ant. pit and inhibit prolactin) Suckling however, inhibits dopamine secretion and thus increases prolactin. The freed prolactin will then go to the breast and cause milk production.

Ejection: Higher brain centers (smell, sight, touch, hear) Stimulate an oxytocin neuron in the hypothal ---> oxytocin released into the blood at the post. pituitary ---> goes to breast and triggers contraction of myoepithelial cells.

Front 34

What does the sex-determining region of the Y Xsome code for?

What 2 things do the testes secrete and what do these do?

How do you develop into a female?

Back 34

- The SDR of the Y xsome codes for the production of H-Y antigen in p.membranes of gonads --> causes them to differentiate into testes.

1. MIF - will cause the mullerian system to regress (no uterus!)
2. Testosterone - will stimulate the wolfian ducts to become male reproductive tract. Test will also be converted (by 5aRed) to DHT which cause males external genitalia

** In the absence of Y --> no testes --> no MIF and no test to save the wolfian --> FEMALE!

Front 35

What happens to E and NEP during hypoglycemia?
What is the effect?

Back 35

When blood sugar is low the adrenal medulla will release EP and NEP.
EP and NE will induce gluconeolysis in liver and skeletal muscle = increasing BS. Their a-adrenergic stimulation will also inhibit the release of insulin thereby limiting the bodies ability to clear the glucose (these effects last longer). If endogenous insulin is compromised (ie DM) then effects amplified.

Front 36

What is the biosynthetic pathway for the synthesis from Phe to NE?
What is one positive stimulator and 2 inhibitors of this pathway?

Back 36

Phenylalanine ---> Tyrosine --> L-Dopa ---> Dopamine ---> EP ---> NE
** dopamine and EP will inhibit the tyrosine Hydroxylase that makes L-Dopa! High-levels of glucocorticoids will stimulate the PNMT that converts EP to NE.

Front 37

What are the various adrenal layers from capsule to medulla?
What does each layer mainly secrete?
How does adrenal structure change from fetus to adult?

Back 37

Capsule --> Zona Glomerulosa (Aldosterone)
---> Fasiculata (glucocorticoids)
---> Reticularis (sex hormones
---> Medulla (catecholamines)
Fetal cortex is HUGE b/c it secretes ++ sulphated androgens that get converted to estrogen by the placenta

Front 38

List the steps from Stress to the release of cortisol.
How is this axis regulated?

Back 38

Stress will cause the Hypothalamus to release CRH/ADH into the hypophyseal portal system. The CRH (pulses) will cause the ant. pituitary to convert POMC ---> ACTH. The ACTH will stimulate adrenal growth (H-trophy & plasia)* and the release of cortisol.
* this is why long-term therapy causes atrophy
Cortisol will have neg feedback on ACTH release, POMC conversion and CRH.

Front 39

For each of the following glucocorticoid actions, state the function (F) and (R)
1. Metabolic (4 each)
2. Permissive (1)
3. Immunosuppressive (1)
4. Behavioural (1)

Back 39

1. Metabolic
- F:incr hepatic Gneogenesis, R:inc aa ---> glucose
- F: Incr protein catabolism R:incr aa in the blood
- F: decr tissue glucose uptake (except brain) R: more glucose for brain
- F: lipolysis R: more FFA in the blood to be available for the brain

Permissive:
F: facilitates catecholamines, R:incre cardiovascular responses during stress

Immunospressive:
F: supresse immune response R:less inflammation

Behavioural:
F: affects mood/behavior/memory/learning, R: will alter cognitive functioning (detrimental in long term)

Front 40

What does each of the * marked precursors become?
Cholesterol --->
/
Pregnane* --->
/
Andrtostane* --->
/
Estrane --->

Back 40

Pregnane* ---> Progesterone + corticosteroids (mineral & gluco)
/
Andrtostane* ---> Androgens
/
Estrane ---> Estrogens

Front 41

What is the most important enzyme in steroideogenesis?

** pearl: each area of the adrenal gland contains a compliment of enzymes specific to that areas function!

Back 41

Desmolase! A lack of this enzyme is incompatible with life!! Need this to convert cholesterol into pregenolone, the precursor for ALL steroid hormones!

Front 42

The loss of which 2 adrenal enzymes would cause them to produce only androgens? What would be the effect of this (on a person)

What is the ratio of cortisol : corticosterone? Which form is active?

Back 42

21 B - Hydroxylase and 11 B hydroxylase ---> will push pathway to create testosterone and this will cause virilization (masculine)

7 Cortisol : 1 Cortisterone <---inactive!

Front 43

ACTH will bind to a receptor on which type of cell?
This will activate the TF known as SF-1--->enzyme synthesis to convert Pregnenolone to 17-OH-progesterone either via ________ or ________. The 17-OH-progesterone is then converted to _________ by __________. This is then converted to Cortisol by __________.

Back 43

ACTH binds receptors on Fasiculata cells.
SF-1--->enzyme synthesis to convert Pregnenolone to 17-OH-progesterone either via 17-OH -PREGENOLONE or PROGESTERONE. The 17-OH-progesterone is then converted to 11-DEOXYCORTISOL by 21-B-HYDROXYLASE. This is then converted to Cortisol by 11-B-HYDROXYLASE.

Front 44

HOw long is the cortisol half life? When do levels peak? Fall?
How much of cortisol is bound (and to what?)
When would want excess cortisol to be bound (inactive)?

Back 44

60-90min
Peak at 7am and fall between 7pm-12am
Cortisol will increase the glucose in the blood thus cortisol will peak in the morning to counteract overnight fasting.
95% is bound to CBG >> Albumin
Increased CBG is produced by the liver during pregnancy and this is to mop-up excess cortisol as it is damaging to the fetus which is also making cortisol (if not enough CBG ---> cushings)

Front 45

What enzyme will:
cortisol <----> cortisone
cortisol -*---> cortisone
Which of the above is active?
Where would you find the second (*) enzyme and why?
How does cortisone cream work?
How is cortisol excreted?

Back 45

11-B-Hydroxysteroid 1
11-B-Hydroxysteroid 2
Would find type 2 in the kidneys; 11-B-HSD 2 will "chew up" any excess cortisol to prevent it from binding the Mcorticoid receptors there (saves the receptors for aldosterone)
Also found in the fetus b/c that little guy needs protection from cortisol b/c glucocorticoids can inhibit growth.
11B-HSD 1 in the skin will activate the cortisone.
Converted to soluble metabolites in the liver and most of these are lost in the urine

Front 46

What enzyme is missing from the zona reticularis? What implications does this have?
What regulates the products of the reticularis? How do the products compare in terms of potency?

Back 46

There is no 21-B-Hydroxylase and thus the only thing it is capable of producing are androgens.
ACTH controls the release of androgens (99.9% of which are sulphoconjugated).
Potency: DHEA << Testosterone

Front 47

What enzyme is missing from the glomerulosa?

Back 47

17-a-Hydroxylase