Lecture Notes on Hormones and Metabolism

Growth Hormone and Bone Growth

• Growth hormone affects normal body function and influences growth and development.
• It promotes the lengthening of skeletal bones through the proliferation of chondrocytes, cartilage-type cells associated with the epiphyseal plate.
• The epiphyseal plate, located near the ends of bones, is the site of growth; growth occurs from either end of the bone.
• Growth hormone stimulates chondrocytes to proliferate and extend bony tissue.

Dysregulation of Growth Hormone

• Pre-puberty: Uncontrolled growth of long bones occurs with excessive growth hormone.
• Pre-puberty: Growth hormone deficiency leads to a lack of normal growth and development.
• Post-puberty: Growth hormone no longer affects the epiphyseal plate but stimulates cartilage growth around joints and facial features (nose, ears), leading to morphological changes.

Hormonal Regulation via Hypothalamus and Pituitary

• Some hormones, like growth hormone, are secreted directly from the anterior pituitary.
• Others, such as those affecting the adrenals and thyroid gland, involve an additional step due to other target tissues.

Thyroid Gland and Thyroxine

• The hypothalamus affects the pituitary, which secretes TSH (thyroid-stimulating hormone), which affects the thyroid gland.
• The thyroid gland then secretes thyroxine (T4).
• Thyroxine is a modified amino acid derived from thyroglobulin with incorporated iodine residues.
• T4 is converted to T3 (triiodothyronine) within cells, which is the active mediator of changes in cellular characteristics.
• T3 directly affects gene expression.

Effects of Thyroxine

• Overall effect: regulation of metabolic activity.
• Hyperthyroidism: High metabolic rate, skinny despite normal or increased food intake, elevated respiration rate and body temperature, thermal discomfort in hot weather.
• Hypothyroidism: Low body temperature, obesity, decreased basal metabolic rate.

Adrenals and Hormones

• The hypothalamus-pituitary axis also influences the adrenals, leading to the secretion of glucocorticoids and mineralocorticoids.
• Dysregulation examples: Cushing's (too much glucocorticoids) and Addison's (too little glucocorticoids) diseases.

Tissue-Specific Hormones

• Hormones from the pancreas and other tissues have tissue-specific effects and may involve some neural innervation but not necessarily through the hypothalamus-pituitary axis.

Pancreatic Hormones

• The pancreas has both exocrine (secretion into the gastrointestinal tract) and endocrine functions.
• Endocrine function (2% of pancreatic tissue) is carried out by islets of Langerhans, which contain:
  • Beta cells: secrete insulin (most abundant).
  • Alpha cells: secrete glucagon (next abundant).
  • Delta cells: secrete somatostatin (least abundant).
• These hormones are proteins, products of gene expression, modified and stored in vesicles for quick release.
• Release is triggered by external signals via signal transduction.

Insulin Secretion

• Biphasic release:
  • Initial release of stored insulin from vesicles.
  • Sustained release due to new insulin production from gene expression during prolonged elevated blood glucose levels.

Neural Component

• The parasympathetic nervous system influences insulin secretion.
• Insulin secretion is facilitated by:
  • Elevated glucose.
  • High amino acids.
  • High free fatty acids.
  • Volatile fatty acids (VFAs).

Ruminant Metabolism

• Ruminants constantly produce VFAs due to rumen microflora, leading to a basal level of insulin secretion.
• Ruminants don't experience large fluctuations in glucose concentrations compared to monogastric animals.

Effects of Insulin on Metabolism

• Insulin affects multiple processes due to signal transduction divergence.
• Liver:
  • Stimulates glycogen synthesis.
  • Stimulates lipogenesis.
  • Inhibits gluconeogenesis.
• Muscle:
  • Stimulates glucose uptake.
  • Stimulates glycogen biosynthesis.
  • Stimulates protein biosynthesis (anabolic).
• Adipose tissue:
  • Stimulates glucose uptake.
  • Stimulates lipogenesis.
  • Decreases lipolysis (anabolic).

Diabetes Mellitus

• Type 1: Lack of insulin secretion leads to a pseudo-starvation response, catabolic metabolism, lipid and protein mobilization, and potential ketoacidosis.
• Type 2: Receptor downregulation due to overstimulation from excessive food intake.
• Mobilizing lipids leads to increased acetyl CoA and ketogenesis, potentially causing diabetic ketoacidosis.

Glucagon and Somatostatin

• Insulin and glucagon have counteracting effects.
• Somatostatin dampens the effects of various hormones.

Calcium Homeostasis

• Calcium is crucial as a cell signaler.
• Milk fever (hypocalcemia) in dairy cows: Post-calving, low calcium levels lead to recumbency; calcium replacement quickly restores function due to calcium's role in nerve and muscle function.

Key Regulators

• Parathyroid hormone (PTH) from the parathyroid gland.
• Calcitonin from the thyroid gland.
• Vitamin D influences calcium uptake in the gastrointestinal tract.
• Calcium is essential for nerve cell conduction and muscle contraction.

Parathyroid Hormone

• Increases in response to low plasma calcium.
• Increases calcium reabsorption in kidneys.
• Activates vitamin D, increasing calcium absorption in the gastrointestinal tract.

Hyperparathyroidism

• Excess PTH leads to calcium mobilization from bones, weakening skeletal structure and causing fractures or lameness and loosening of teeth.

Hypoparathyroidism

• Too little PTH leads to various effects.

Calcitonin

• Opposes PTH.
• Drives calcium back into bones.
• Inhibits calcium uptake from the gastrointestinal tract.
• Decreases calcium reabsorption in the kidneys.

Activated Vitamin D

• Receptor affects gene expression, leading to the production of calcium pumps that move calcium from the gastrointestinal tract into circulation.

Final Exam Information

• 40 multiple-choice questions (MCQs).
• Two short answer questions (choice of A or B for the first question).
• The second short answer question is about case studies.
• All material from the thirteen weeks is testable.
• The exam will focus on understanding, not memorizing millimolar values.

Case Studies

Cloncurry Calf (Urea Cycle Disruption)

• Calf exhibits aberrant behaviors and dies quickly.
• Blood analysis shows high citrulline, glutamine, ammonia, and low blood urea nitrogen.
• Points to disruption in the urea cycle, primarily in the liver.
• Genetic disorder affecting the arginine succinate synthetase enzyme.
• Ammonia diffuses into the brain, disrupting energy production and neurotransmission, leading to cerebral edema (swelling of brain cells).

Ovine Pregnancy Toxemia (Ketosis)

• Ewe with twin lambs showing signs of negative energy balance due to drought and increased glucose demands.
• Biochemical analysis indicates high blood urea nitrogen, low glucose, elevated non-esterified fatty acids (NEFAs), high ketones, and low cholesterol.
• Liver discoloration (hyperlipidemia).
• Nutritional deficiency leading to ketoacidosis.
• Acetone smell due to ketone body production.
• Low glucose, high ketones, high NEFAs, and hepatic lipid accumulation are indicative of ovine pregnancy toxemia.

Molybdenum Toxicity (Urinary problem)

• Calf born and dies quickly with neurological impairment.
• Points to disruption in urea cycle, primarily in brain.
• Genetic disorder
• Elevated amino acids and keto acids in plasma and urine indicate a problem with amino acid metabolism.
• Elevated leucine, isoleucine, and valine suggest maple syrup urine disease.
• Myelin edema occurs, where fluid is drawn out of cells into spaces, causing the brain to malfunction.