Mstn Ii - Lecture 25

Front 1

Adrenogenital Syndrome

Back 1

- precocious puberty due to gross production of androgens ultimately due to gucocorticoid (GC) insufficiency.

- to cure/stall syndrome, give cortisol

Front 2

weak androgen

Back 2

DHEA

binds to the androgen receptor weakly.

Front 3

strong androgen

Back 3

testosterone
dihydrotestosterone (DHT)

binds to the androgen receptor strongly

Front 4

DHEA

Back 4

double bond in the delta5 position
OH at C3
carbonyl at C17

Front 5

Testosterone and DHT

Back 5

double bond at the delta4 position
carbonyl at C3
OH at C17

Front 6

DHT

Back 6

reduced form of testoterone
- doube bond in ring A has been reduced by 5 alpha reductase.

stronger than testosterone. Most of the tostosterone's effects are actually brought about by DHT

very little made in testes. It's converted in the priphery.

Front 7

3 beta hydroxysteroid dehydrogenase

(3betaHSD)

Back 7

doesn't matter on which step in the testosterone synthesis it works.

Parallel steps going down using 3 beta HSD

Front 8

levels of androgen and hair growth:

low:

high:

Back 8

low: promotes hair growth

high: baldness

Front 9

aromatase

Back 9

convert testosterone to estradiol

aromatizes ring A.

found mostly in the adipose tissue and the ovaries.

Front 10

GnRH

Gonadotropin-releasing hormone

Back 10

works on the pituitary to increase secretion of LH and FSH.

Front 11

LH

Back 11

primarily works on the Leydig cells -> produce testosterone

Front 12

Testosterone

endocrine:

paracrine:

Back 12

endo: negatively feedbacks onto both the pituitary and the hypothalamus

paracrine: stays within the testes, it stimulates the Sertoli cells in the seminiferous tubules.

Front 13

Androgen binding protein

(ABP)

Back 13

in the Sertoli cells, helps to bind tightly to androgens.

Front 14

Carrier protein for androgens in the bood:

Back 14

is exactly like ABP but with a different glycosylation pattern.

Androgens are hydrophobic, therefore they need carrier proteins.

Front 15

TeBG, Albumin

Back 15

carrier proteins of Testosterone

Front 16

TeGB

Back 16

Carrier protein for Dihydrotestosterone

Front 17

TeBG (weak)

Back 17

carrier protrein for estradiol

Front 18

Albumin

Back 18

carrier protein of Estrone

Front 19

CBG (corticosterone binding globulin)

Back 19

carrier protein for progesterone

Front 20

Testosterone binds to the androgen receptor and:

Back 20

leads to gonadotropin regulation, increased spermatogenesis, and stimulates the Wolffian duct development.

Front 21

DHT binds to the androgen receptor and:

Back 21

causes external virilization and sexual maturation at puberty

Front 22

5 alpha reductase deficiency

Back 22

- male on the inside, but female on the outside
- have testosterone, but lack the enzyme that convert it into DHT.
- no external virilization which causes the default external genitalia.
- apparent vagina opens into a blind pouch b/c the Mullerian inhibiting factor prevents the development of uterus, fallopian tubes, upper vagina.
- Testes do not descend. At purberty, masculine secondary sex features appear b/c massive amounts of testosterone produced by the inguinal testes achieve similar effects as DHT

Front 23

primary hypogonadism

Back 23

faulty testicles

treated with testosterone b/c their testicles fail and so they have no testoterone.
Enlargement of the penis is due not to the local effect of testosterone, but due to the endocrine effect of testosterone.

Front 24

Testicular Feminization Syndrome

Back 24

- Reigenstein Syndrome = bad androgen receptors
- have breast development due to insufficient or dysfunctional androgen receptors.
- high testosterone levels ead to increased levels of estrogens, converted by aromatase -> breast
- Complete testicular fminization = complete female phenotype on the outside.
- Androgens come from the inguinal testes.
- have testes removed to avoid testicular cancer, and be given estrogen therapy.

Front 25

Pubic Hair Development

Back 25

for both males and females, pubic hair is due to the action of testosterone.

Front 26

Theca Cells

Back 26

make progesterone and testosterone

no aromatase

Front 27

granulosa cells

Back 27

have aromatase, but no 17 alpha reductase

cannot make testosterone from progesterone

release progesterone and estradol

Front 28

In fetus, pregnenoone:

Back 28

- cannot be made into progesterone, b/c no 3 beta HSD
- so all pregnenolone made by the adrenal cortex (fetal) must be made into DHEA or DHEA-sulfate.

Front 29

DHEA and DHEA-sulfate in the fetus:

Back 29

is carried in the fetal blood to the fetal liver which has 16 alpha-hydroxylase

Front 30

16 alpha-hydroxylase

Back 30

convert DHEA into 16 alpha-hydroxy-DHEA, which again enters the blood and goes to the placenta

Front 31

16 alpha-hydroxyDHEA in the placenta:

Back 31

converted to estriol (E3) via aromatase.

Front 32

Main estrogen during prognancy:

Back 32

Estriol (E3)

cleared from the body in the maternal liver by making it more hydrophilic by glucuronic acid conjugation.

Front 33

Placenta can also convert pregnenolone into:

Back 33

progesterone, which can travel via circulation back to the fetal adrenal cortex, which may use it as a precursor to cortisol.

Front 34

Tamoxifen

Back 34

- given as a treatment for estrogen receptor for breast cancers/tumors
- estrogen antagonist effects
- Estrogen acts as a growth factor, blocking it = decreased size of the tumor.