L17/L4 RH steroid hormone receptors 1

print biosynthesis

learning outcomes

adrenal gland

cortisol & aldosterone

ovaries

oestrogen & progesterone

testes

testosterone

what are steroid hormones

• lipid-soluble chemical messengers

• syn in glands

steroid hormone sysnthesis

• synthesised primarily in the adrenal glands and gonads (ovaries and testes)

• synthesised from cholesterol

• synthesis largely regulated at the initial steps of cholesterol mobilisation and transport into the mito matrix for conversion into pregnenolone

steroid hormone function

• regulate energy metabolism and stress response - glucocorticoids

• salt balance - mineralocorticoids

• sexual devel and function - androgens and oestrogens

SH biosynthesis

• derived from cholesterol

• first step in rate-limiting: cholesterol → pregnenolone

IC receptors types image

Class I IC receptors

• SH receptors

• cytosolic monomers bound to heat-shock prots

• once activated, form dimers and transloc. to nucleus to induce transcription of target genes

Class II IC receptors

• e.g. TR, RAR, VDR

• retained in nucleus

• assoc. with DNA

• actively repressing transcription until ligand arrives

classification of nuclear receptor superfamily

IC SHRs

• upon ligand binding, SHRs transloc. into nucleus

• pattern similar for all SHRs (except oestrogen)

• oestrogen receptor is principally nuclear

examples of ligands for SHRs

activation of cytosolic-resident receptors

• ability of cytosolic resident Rs to bind to ligand dependent on chaperone proteins (e.g. HSP90) and accessory molecules (e.g. regulatory chaperone p23)

• enables R complex to transloc. to nucleus

• complex dissociates and enables dimerised Rs to bind to the DNA response element on target promoter

• induces transcription of target genes

• the used R loses it’s hormone, associates with chaperone where they are degraded or exported back to cytoplasm

activation of cytosolic-resident receptors image