Chapter 18: The Pituitary Gland

The Pituitary Gland

• Located in a pocket of the sphenoid bone at the base of the brain
• Acts as a coordinating center for control of many downstream endocrine glands
• Can be considered to consist of at least two (and in some species, three) separate endocrine organs

Hormones Secreted by the Anterior Pituitary

• Thyroid-stimulating hormone (TSH, thyrotropin)
• Adrenocorticotropic hormone (ACTH)
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Prolactin
• Growth hormone
• Prolactin acts on the breast
• Remaining five hormones are tropichormones, stimulating secretion of hormonally active substances by other endocrine glands or the liver and other tissues

Growth Hormone Biosynthesis & Chemistry

• The growth hormone-hCS cluster contains five genes on the long arm of human chromosome 17
• One gene codes for the most abundant (“normal”) form of growth hormone
• A second gene codes for the variant form of growth hormone
• Two genes code for human chorionic somatomammotropin (hCS)
• The fifth gene is probably an hCS pseudogene
• Growth hormone secreted into the circulation by the pituitary gland is a complex mixture of different peptides with varying degrees of posttranslational modifications

Plasma Levels, Binding, & Metabolism

• Circulating growth hormone is bound to a plasma protein that is a large fragment of the extracellular domain of the growth hormone receptor
• Approximately 50% of the circulating pool of growth hormone activity is in the bound form
• Basal plasma growth hormone level measured by radioimmunoassay in adult humans is normally less than 3 ng/mL
• Growth hormone is metabolized rapidly, at least in part in the liver
• Half-life of circulating growth hormone in humans is 6–20 min
• Daily growth hormone output in adults is 0.2–1.0 mg/d

Growth Hormone Receptors

• Growth hormone receptor is a 620-amino-acid protein with a large extracellular portion, a transmembrane domain, and a large cytoplasmic portion
• Member of the cytokine receptor superfamily
• Growth hormone has two domains that can bind to its receptor, and dimerization is essential for receptor activation
• Growth hormone activates many different intracellular signaling cascades, including the JAK2–STAT pathway

Effects on Growth

• Growth hormone stimulates growth in young animals by accelerating chondrogenesis and increasing bone matrix deposition
• In animals with closed epiphyses, growth hormone produces the pattern of bone and soft tissue deformities known as acromegaly
• Growth hormone does not stimulate β cells of the pancreas directly but increases the ability of the pancreas to respond to insulinogenic stimuli

Somatomedins

• Growth hormone effects on growth, cartilage, and protein metabolism depend on an interaction between growth hormone and somatomedins
• Somatomedins are polypeptide growth factors secreted by the liver and other tissues
• There are a variety of different somatomedins, including insulin-like growth factor I (IGF-I, somatomedin C) and IGF-II
• These factors are closely related to insulin, except that their C chains are not separated and they have an extension of the A chain called the D domain