Comprehension Passage

A passage is given with 5 questions following it. Read the passage carefully and choose the best answer to each question out of the four alternatives.

Amino acid-derived hormones and polypeptide hormones are not lipid-derived (lipid-soluble or fat-soluble); therefore, they cannot diffuse through the plasma membrane of cells. Lipid-insoluble hormones bind to receptors on the outer surface of the plasma membrane, via plasma membrane hormone receptors. Unlike steroid hormones, lipid-insoluble hormones do not directly affect the target cell because they cannot enter the cell and act directly on DNA. The binding of these hormones to a cell surface receptor results in the activation of a signalling pathway; this triggers intracellular activity to carry out the specific effects associated with the hormone. The hormone that initiates the signalling pathway is called a first messenger, which activates a second messenger in the cytoplasm. One very important second messenger is cyclic adenosine monophosphate (cAMP). When a hormone binds to its membrane receptor, a G protein that is associated with the receptor is activated. When a hormone is not bound to the receptor, the G protein is inactive and is bound to guanosine diphosphate or GDP. When a hormone binds to the receptor, the G protein is activated by binding guanosine triphosphate, or GTP, in place of GDP. After binding, GTP is hydrolyzed by the G protein into GDP and becomes inactive. The activated G protein in turn activates a membrane-bound enzyme called adenylyl cyclase. Adenylyl cyclase catalyzes the conversion of ATP to cAMP. cAMP, in turn, activates a group of proteins called protein kinases, which transfer a phosphate group from ATP to a substrate molecule in a process called phosphorylation. 

Where do lipid-insoluble hormones binds?

1
receptors on the outer surface of the plasma membrane
2
receptors on the outer surface of the mitochondria
3
receptors on the outer surface of  the nucleus
4
receptors on the inner surface of the plasma membrane

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