Lecture 1

Question 1

Estrogen

Answer 1

the development and maintenance of female characteristics

Question 2

Progesterone

Answer 2

preparation for and maintenance of pregnancy

Question 3

Androgen

Answer 3

the development and maintenance of male characteristics

Question 4

Structure

Answer 4

cholesterol
17B-estradiol - aromatic ring - aromatase converts androgens to estrogens
progesterone
testosterone (aromatase) - oestrogen

Question 5

Glucocorticoids

Answer 5

e.g. cortisol

stress hormones
steroid family
inflammatory pathways and metabolism
Stress during pregnancy can alter fetal growth pre- and postnatally

Question 6

Receptors

Answer 6

Hormone action requires receptor protein in target tissues

The major steroid receptors act in the cell nucleus

Question 7

Receptor staining

Answer 7

Immunohistochemistry

localising nuclear steroid receptor (brown) in tissue sections

blue stain - DNA

Question 8

Steroid receptors - binds to response element

Answer 8

the androgen receptor (AR)

estrogen receptor (ER)

progesterone receptor (PR)

glucocorticoid receptor (GR)

Question 9

Detection of receptor expression identifies a target tissue

Answer 9

the placenta has glucocorticoid receptor - red nuclei stain for GR

Question 10

Nuclear receptor superfamily

Answer 10

Proteins with 2 binding sites - hydrophobic ligand (steroid) and DNA

dual binding function is crucial for their ability to alter the repertoire of genes being expressed by target cells

Question 11

Receptors transcription factors have a modular structure

Answer 11

steroid binds to DNA binding domain and transcriptional regulation domain make a steroid hormone-receptor complex which binds to DNA response element

Question 12

Steroid hormone action

Answer 12

Binding of the [steroid-steroid receptor] complex to the SRE on DNA alters the rate of transcription – so mRNA abundance alters (with downstream effects on protein abundance)

Question 13

Primary and secondary steps in the transcriptional response

Answer 13

binds to DNA and then binds again

Question 14

Epididymis

Answer 14

sperm maturation

Question 15

Seminiferous tubules

Answer 15

sperm production

Seminiferous tubules are surrounded by
myoid cells.

The spaces between the tubules contain connective tissue, blood vessels, and Leydig (interstitial) cells.

Question 16

Testis

Answer 16

Epithelium of seminiferous tubules surrounded by myoid cells.

The spaces between the tubules contain connective tissue, blood and lymphatic vessels, and interstitial cells.

Question 17

Steroid synthesis in the testis

Answer 17

LH binds to LHR on Leydig cell which converts cholesterol to testosterone which then enters the Sertoli cell to convert testosterone to DHT by 5alpha reductase as FSH binds to Sertoil FHSR

Question 18

Testosterone

Answer 18

Actions in the testis:
Export to blood, lymph, testicular secretions

testosterone acts back on AR in the Leydig cell to promote survival - autocrine effect

Question 19

DHT

Answer 19

DHT is a more potent androgen than testosterone

Question 20

Testis + testosterone

Answer 20

Cells in the testis not only MAKE testosterone, they also bear receptors (AR)

So they respond to testosterone and other androgens, by altering their profile of gene expression and therefore function = mRNA repertoire

Question 21

AR present in

Answer 21

Sertoli cells
Leydig (interstitial) cells
Myoid cells

Question 22

Androgen receptor knock out

Answer 22

The AR-null (ARKO) male mouse develops with very small testes (20% normal)

Spermatogenesis is arrested at the spermatocyte stage (See lecture 6)

They have a female appearance

The ARKO female has reduced litter sizes – androgens are important in the female too

Question 23

Sex steroid synthesis

Answer 23

Androgens are the biosynthetic precursors of estrogens

In men, estradiol is produced by the testis (roughly 20% of the amount found in non-pregnant women).

Question 24

Male mice that lack estrogen show highly impaired spermatogenesis

Answer 24

Aromatase knock-out mice lack estrogen
(note: the aromatase gene is known as Cyp19)

Spermatogenesis begins, but then fails