SF-1 Flashcards
What are orphan nuclear receptors?
Receptors for which there is no known ligand. They may be constitutively active and may represent primitive nuclear receptors as they are similar in structure to steroid hormone receptors.
Which domains of steroid receptors are responsible for:
a) DNA binding
b) shape changes
c) dimerisation
d) nuclear translocation and binding of HSPs
a) C
b) D
c) E-F
d) E
In light of this: what regions are likely to be conserved/variable?
All of the above are conserved. A&B are variable
Where does SF-1 bind to?
The gonadotroph specific element (GRE)
How can nuclear receptor gene expressing/suppressing abilities be regulated?
Binding to HSPs prevents nuclear translocaiton
They need to dimerise with another receptor
Phosphorlyation can enhance binding ability and coactivator/repressor recruitment
Why are changes to expression levels unlikely to be a method of regulation?
It is too slow
What is the role of SF-1?
It is essential for development of pituitary: gonadotrophs, gonadal cells and adrenocortical cells
What is the phenotype of SF-1 mutants?
Streak female gonads and little adrenal tissue - which can quickly lead to death.
Male gonads are often absent with persistent mullerian structures.
GnRH neurone are intact and so are gonadotrophs but even so there is little production of the gonadotrophin hormones
How is SF-1 regulated?
Phosphorylation of specific amino acids e.g. PKA and ERK @ S203
Sumoylation of lysine residues.
What does the alpha-GSU gene encode?
alpha chain of LH/FSH and TSH
What is its relationship to SF-1?
alpha-GSU has a GRE.
How is alpha GSU transcription “turned on”?
It is a result of GPCR activation by PACAP or GnRH.
What is the relationship between these molecules and SF-1?
The presence of SF-1 enhances basal and PACAP mediated alpha-GSU transcription. This seems to be due to MAPK signalling (mitogen activated protein kinase, this is an ERK).
What evidence is there for BDNFs role in obesity?
Removal of the VMH leads to ravenous feeding behaviour.
How is this chemical related to SF-1?
BDNF promotor has at least 6 SF-1 binding domains.
SF-1 k/o have much lower BDNF and have increased weight gain compared to WT mice.
