Growth Hormone Synthesis and Regulation

Growth Hormone Synthesis

• Growth hormone (GH) is a peptide hormone synthesized and secreted by somatotroph cells in the anterior pituitary.
• GH is stored in granules until released by GHRH (Growth hormone releasing hormone) from the hypothalamus.
• GH is part of a family of hormones including placental lactogens (placental chorionic somatomammotropins) and prolactin.

Growth Hormone Regulation

• GHRH, produced in the arcuate nucleus of the hypothalamus, stimulates GH secretion via cAMP/PKA pathway.
• Somatostatin (SS), produced in the periventricular region of the hypothalamus, suppresses GH release by inhibiting cAMP/PKA signaling.

Growth Hormone Secretion

• GH secretion follows a diurnal pattern, peaking at night, especially during non-REM deep sleep.
• Half-life of GH is approximately 20-25 minutes.
• Factors that suppress GH secretion include: GH, IGF-1, hyperglycemia, cortisol, and xenobiotics (e.g., endocrine disruptors).
• Factors that stimulate GH secretion include: energy deficiency (hypoglycemia, vigorous exercise, fasting), certain amino acids (protein-rich meal), hormones (sex steroids, glucagon), and deep sleep.

Growth Hormone Action

• GH acts directly on its target cells by binding to and activating the GH receptor.
• This initiates a JAK/STAT-based intracellular signaling cascade, leading to transcription of IGF-1.
• In the liver, GH stimulates IGF-1 production and release.
• GH has both indirect (via IGF-1) and direct effects, impacting linear growth, gluconeogenesis, lipolysis, and glucose uptake.

IGFs and Signaling

• IGF-1 and IGF-2 are peptide hormones with insulin-like activity.
• IGF-1 is primarily produced by the liver in response to GH and promotes growth-promoting effects.
• IGFs circulate mostly bound to carrier proteins (IGFBPs), which prolong their half-life and regulate their biological effects.
• IGF-1 receptors are structurally similar to insulin receptors; signaling cascades are similar.
• IGF-1 levels increase during childhood, peak at puberty, and gradually decrease in adulthood.

Growth Hormone Regulation

• GH and IGF-1 are regulated by negative feedback loops.
• IGF-1 suppresses GHRH release and increases somatostatin release.
• Both GH and IGF-1 negatively feedback to the somatotrophs, decreasing GH release,
• GH excess leads to conditions such as acromegaly (in adults) or gigantism (in children).
• Low GH production may lead to dwarfism, as in Laron syndrome.