Lecture 1 Flashcards
(24 cards)
Estrogen
the development and maintenance of female characteristics
Progesterone
preparation for and maintenance of pregnancy
Androgen
the development and maintenance of male characteristics
Structure
cholesterol
17B-estradiol - aromatic ring - aromatase converts androgens to estrogens
progesterone
testosterone (aromatase) - oestrogen
Glucocorticoids
e.g. cortisol
stress hormones
steroid family
inflammatory pathways and metabolism
Stress during pregnancy can alter fetal growth pre- and postnatally
Receptors
Hormone action requires receptor protein in target tissues
The major steroid receptors act in the cell nucleus
Receptor staining
Immunohistochemistry
localising nuclear steroid receptor (brown) in tissue sections
blue stain - DNA
Steroid receptors - binds to response element
the androgen receptor (AR)
estrogen receptor (ER)
progesterone receptor (PR)
glucocorticoid receptor (GR)
Detection of receptor expression identifies a target tissue
the placenta has glucocorticoid receptor - red nuclei stain for GR
Nuclear receptor superfamily
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
Receptors transcription factors have a modular structure
steroid binds to DNA binding domain and transcriptional regulation domain make a steroid hormone-receptor complex which binds to DNA response element
Steroid hormone action
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)
Primary and secondary steps in the transcriptional response
binds to DNA and then binds again
Epididymis
sperm maturation
Seminiferous tubules
sperm production
Seminiferous tubules are surrounded by
myoid cells.
The spaces between the tubules contain connective tissue, blood vessels, and Leydig (interstitial) cells.
Testis
Epithelium of seminiferous tubules surrounded by myoid cells.
The spaces between the tubules contain connective tissue, blood and lymphatic vessels, and interstitial cells.
Steroid synthesis in the testis
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
Testosterone
Actions in the testis:
Export to blood, lymph, testicular secretions
testosterone acts back on AR in the Leydig cell to promote survival - autocrine effect
DHT
DHT is a more potent androgen than testosterone
Testis + testosterone
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
AR present in
Sertoli cells
Leydig (interstitial) cells
Myoid cells
Androgen receptor knock out
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
Sex steroid synthesis
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).
Male mice that lack estrogen show highly impaired spermatogenesis
Aromatase knock-out mice lack estrogen
(note: the aromatase gene is known as Cyp19)
Spermatogenesis begins, but then fails
