Growth Hormone and IGF-1 - Lecture Flashcards

A comprehensive set of Q&A flashcards covering GH and IGF-1 physiology, signaling, regulation, metabolic and growth effects, clinical conditions (gigantism/acromegaly), age/sex differences, and summary study outcomes.

Where is growth hormone (GH) synthesized and stored, and what percentage of anterior pituitary cells are somatotrophs?

GH is synthesized in anterior pituitary somatotrophs, which make up about 40–50% of the cells in the anterior pituitary; it is stored in large granules within these cells.

What is the major mediator through which many GH effects are executed, and what is the most common Somatomedin?

The liver secretes Somatomedins (IGFs) that mediate many GH effects; the most common Somatomedin is Somatomedin C, also called IGF-1.

What hormones regulate the synthesis and secretion of growth hormone, and what are their primary actions?

GHRH (growth hormone releasing hormone) induces synthesis and secretion of GH, while somatostatin inhibits synthesis and secretion; GHRH pulses trigger pulsatile GH release.

How does sleep influence GH secretion?

GH secretion increases during sleep, particularly in slow-wave (deep) sleep, and this pattern contributes to higher GH activity in early sleep stages.

Describe the hypothalamic–liver axis with respect to GH and IGF-1 travel.

GH and IGF-1 travel in the blood both in free form and bound to plasma proteins; IGF-1 produced mainly by the liver acts as a mediator of GH effects throughout the body.

What receptors mediate GH and IGF-1 signaling, and what are their key subunits or associated kinases?

GH receptor is part of a receptor family associated with tyrosine kinases (via JAK activation); the IGF-1 receptor has α and β subunits and dimerizes upon IGF-1 binding.

What are the major post-receptor signaling pathways activated by GH and IGF-1?

JAK/STAT, IRS (Insulin Receptor Substrate), MAPK (RAS-MAPK pathway), and AKT signaling are key post-receptor responses; these pathways promote survival, proliferation, and growth-related effects.

List three growth-promoting effects of GH–IGF-1 on bones and joints.

1) Stimulates chondrocyte function and cartilage growth; 2) Increases bone mass and mineral content; 3) Promotes osteoblastic activity and bone formation.

What are the primary metabolic (non-growth) effects of GH on protein, fat, and carbohydrate metabolism?

GH increases protein synthesis (with more amino acid uptake and transcription/translation, and anti-catabolic effects); mobilizes fatty acids and enhances fatty acid oxidation; decreases glucose utilization (anti-insulin effect) and increases hepatic glucose production (gluconeogenesis), contributing to higher blood glucose and insulin resistance in high GH states.

Why is GH often described as diabetogenic when present in high levels?

Because GH raises blood glucose by reducing glucose uptake in muscle and adipocytes and increasing hepatic glucose production, which can lead to insulin resistance and diabetes in some contexts.

What are the growth-promoting effects of GH on visceral organs?

GH causes hypertrophy and hyperplasia of visceral organs, including growth of the heart, lungs, liver, pancreas, GI tract, adrenal glands, and others.

What is the role of IGF-1 in GH signaling and what tissue primarily produces it?

IGF-1 mediates many of GH’s effects; it is primarily produced by the liver in response to GH stimulation, though other tissues also produce IGFs.

What conditions are associated with excessive GH secretion in children and adults, and what causes them?

Gigantism occurs in children before epiphyseal closure due to excessive GH, leading to excessive height; acromegaly occurs in adults after epiphyseal closure, causing enlargement of hands, feet, face, and organs due to a GH-secreting pituitary adenoma.

What is a common underlying cause of gigantism and acromegaly, and what is elevated in the blood?

A benign pituitary tumor secreting excess GH is the most common cause; IGF-1 levels in the blood are elevated due to GH stimulation.

What two clinical risks are increased in patients with gigantism or acromegaly?

Diabetes mellitus (glucose intolerance) and vascular/organ changes (e.g., vascular degeneration, hypertension) are common risks.

How does aging affect the GH–IGF-1 axis?

IGF-1 levels are highest in childhood and peak during puberty; IGF-1 levels decline with aging; GH secretion patterns also change with age.

How do sex hormones influence GH secretion in males and females?

Estradiol stimulates GH secretion with a peak around ovulation; testosterone stimulates GH secretion in males; GH secretion is typically greater in females than males in some contexts.

What is the effect of puberty on GH and IGF-1 activity?

GH and IGF-1 activity is particularly prominent during puberty, contributing to rapid growth and development; puberty is associated with a peak in GH/IGF-1 activity.

What is the relationship between GH and insulin in growth and metabolism?

Growth-promoting effects require normal insulin levels and adequate dietary intake of carbohydrates and protein; insulin supports GH actions on growth and protein synthesis.

What happens to GH release and IGF-1 levels during fasting and hypoglycemia?

Fasting and hypoglycemia stimulate GH release and IGF-1 signaling, helping mobilize energy stores and maintain glucose availability.

What happens to GH secretion with exercise and acute physical stress?

Exercise and physiologic stress stimulate GH secretion, contributing to metabolic and growth-related responses during physical activity.

What are the key differences between childhood gigantism and adult acromegaly in terms of physical changes?

Gigantism (childhood) causes excessive height due to continued linear growth; acromegaly (adult) causes enlargement of hands, feet, facial features, jaw, tongue, and soft tissues after epiphyseal closure; organomegaly can occur in both.

What has research shown about GH administration with resistance training in older men?

GH administration with resistance training increases fat-free mass and whole-body protein turnover, but does not significantly enhance muscle strength or isolated muscle protein synthesis beyond exercise alone; noncontractile tissue may account for much of the FFM gain.

What has research shown about GH administration with resistance training in young men?

GH plus resistance training increases fat-free mass and whole-body protein synthesis more than resistance training alone, but specific skeletal muscle adaptations (e.g., quadriceps protein synthesis, strength) do not show large additional gains.

What were the major findings of the JAMA 2002 randomized trial on GH and sex steroids in elderly participants?

GH with or without sex steroids increased lean body mass and decreased fat mass; some benefits in strength and VO2max were modest or sex-dependent; adverse effects were common (e.g., edema in women, carpal tunnel symptoms, diabetes/glucose intolerance in GH-treated individuals), suggesting risks may outweigh benefits in healthy elderly adults.

What is the note about infant GH deficiency mentioned in the notes?

Infants with growth hormone deficiency are normal in size at birth; growth issues become apparent as growth requires GH signaling after birth.

What is an easy-to-remember key phrase describing GH’s “anti-insulin” action on carbohydrates?

GH decreases glucose uptake in muscle and adipose tissue and increases hepatic glucose production, raising blood glucose and acting as an anti-insulin agent.

What basic physiological effect does GH have on amino acid transport and protein synthesis?

GH increases amino acid transport into cells and stimulates transcription and translation, promoting protein synthesis and contributing to growth and tissue maintenance.

What is a notable effect of GH on collagen and extracellular matrix components?

GH–IGF-1 signaling increases collagen and proteoglycan synthesis, contributing to connective tissue growth and joint/bone health.

What are somatomedins, and what is their broader significance in GH signaling?

Somatomedins are IGFs produced in response to GH that mediate many of GH’s growth-promoting effects; IGF-1 is the principal somatomedin, driving cellular growth and metabolism.

What specific note about GH’s effect on infants and early life growth is mentioned in the notes?

Infants deficit in growth hormone are normal size at birth, with growth effects manifesting postnatally as GH signaling regulates postnatal growth.