Intracellular Receptors (HL) (HL IB Biology)

• Eukaryotes use transcription factors to control gene expression
  • A transcription factor is a protein that controls the transcription of genes by binding to a specific region of DNA
  • If a gene is transcribed and translated then it is expressed in the cell or individual

Ligand activation of gene expression

• Steroid hormones are small, hydrophobic, lipid-based hormones that can diffuse through the cell membrane and can pass directly into the nucleus through nuclear pores
  • Once inside the cell, they can bind to intracellular receptors
• Steroid hormones such as testosterone, progesterone and oestradiol (also known as oestrogen) are ligands responsible for the expression of many genes within a cell
  • Oestradiol is involved in controlling the female fertility cycle and is also responsible for stimulating sperm production in males
  • Up to 100 different genes are controlled by oestradiol

The oestradiol stimulation pathway:

1. 1. Oestradiol diffuses through the cell surface membrane into the cytoplasm
   2. Oestradiol diffuses through a nuclear pore into the nucleus
   3. Within the nucleus, oestradiol attaches to an ERα oestradiol receptor that is held within a protein complex, this causes the ERα oestradiol receptor to undergo a conformational change
   4. The new shape of the ERα oestradiol receptor allows it to detach from the protein complex and diffuse towards the gene to be expressed
   5. The ERα oestradiol receptor binds to a cofactor which enables it to bind to the promoter region of the gene, this stimulates RNA polymerase binding and gene transcription

The oestradiol stimulation pathway

Oestradiol

• Oestradiol is a steroid hormone responsible for regulation of female sexual characteristics amongst other roles
• It is produced in the ovaries, placenta and testes but is regulated by levels of other hormones released from the hypothalamus
• Gonadotropin releasing hormone is first released from the hypothalamus
• This stimulates the release of lutenising hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland
• These hormones together are responsible for control of the menstrual cycle with target cells found in the uterus, breasts and bone marrow of females
• Oestradiol can either inhibit or promote the release of gonadotropin-releasing hormone throughout the menstrual cycle which results in either a positive or negative feedback response

Progesterone

• Progesterone is a steroid hormone responsible for the maintenance of the endometrial lining in preparation for implantation of a fertilised ovum and development of a foetus
• Progesterone also prevents further ovulation during pregnancy
• It is produced by the corpus luteum and placenta
• On entering the cytoplasm of a target cell, progesterone forms a ligand-receptor complex, leading to expression of a range of genes
• One example of a gene transcribed and translated as a result of progesterone is a growth factor which promotes cell proliferation required to continuously replenish the endometrial cells of the uterus