Hormones, Hypothalamus, and Pituitary Gland

Hypothalamus and Pituitary

Introduction

• Focus on hormones and endocrine regulation.
• Aim for a reasonable level of complexity, focusing on relevance to metabolism.
• Hypothalamus and pituitary as key mediators.
• Examine hormones secreted directly and the hypothalamus' role in integrating endocrine regulation.

Hypothalamus-Pituitary Axes

• Posterior pituitary (neurohypophysis).
• Anterior pituitary.
• Discuss examples of dysregulation to understand hormone significance.

Structures

• Small tissues with significant influence on homeostasis, growth, and development.
• Growth hormone impact on developmental growth.
• Hypothalamus and pituitary located at the base of the brain.

Hypothalamus

• Contains neuroendocrine cells (neurons that release hormones).
• These neurons have axons and release signals like typical neurons.

Orientation

• Hypothalamus (top).
• Posterior pituitary (right).
• Anterior pituitary (left).
• Intermediate lobe (minor endocrinological function).

Circulation

• No shared circulation between hypothalamus and posterior pituitary.
• Shared vasculature between hypothalamus and anterior pituitary (important for communication).

Posterior Pituitary

• Focus on key regulators, not all hormones.
• Neurohypophysis relation to the Hypothalamus
• Axons from paraventricular and supraoptic nuclei (neuroendocrine cells in the hypothalamus) extend into the posterior pituitary.
• These axons secrete hormones directly into circulation.
• The relationship with the anterior pituitary is different.

Hormones

• Antidiuretic hormone (ADH) or vasopressin.

• Oxytocin.

• Produced in the hypothalamus and released via the posterior pituitary into circulation.

Peptide Hormones

• Small, with few amino acids.
• ADH and oxytocin are similar but have different effects.

Oxytocin

• Role in milk ejection reflex (milk let-down).
• Contraction of myoepithelial cells in the mammary gland.
• Pavlovian response (e.g., cows releasing milk upon hearing milking machines).
• Neural component: Piglets' squealing or babies' crying can elicit milk let-down.

Other roles

• Parturition (contraction of the myometrium).
• Sperm transport.
• Corpus luteum degradation.
• Changes in the endometrium (influenced by prostaglandin F2 \alpha).
• Prolactin synthesis (important for lactation).

Milk Let-Down Reflex

• Stimulation (e.g., suckling) leads to neural integration and afferent pathway to the brain.
• Release of oxytocin from the hypothalamus into circulation.
• Oxytocin acts on the mammary gland.

Mammary Gland Structure

• Teat canal and gland cistern.
• Complex matrix of ducts leading to alveoli.
• Alveoli: Single layer of mammary epithelial cells that produce milk.
• Milk secreted into the alveolar lumen.
• Myoepithelial cells contract, squeezing alveoli and forcing milk into ducts.
• Ducts constrict, moving milk through the gland and out.

Antidiuretic Hormone (ADH) / Vasopressin

• Influenced by changes in fluid balance.
• Sense of thirst reflects neural integration.

Stimuli

• Decreased blood volume.
• Changes in osmotic potential of blood and intracellular fluid.

Mechanism

• Neural integration and secretion of ADH.
• ADH changes fluid retention in the kidney (recovering water instead of eliminating it in urine).
• Dilution of osmotic potential and potential increase in blood volume.

Production and Release

• Hormones produced in the hypothalamus, packaged in vesicles, and transported down axons.
• Released into circulation via exocytosis.

Stimuli for Vasopressin Release

• Blood osmolarity (osmoreceptors in the hypothalamus).
• Blood volume (receptors in the heart).
• Afferent signals to the brain to stimulate release of ADH or vasopressin.
• Water retention in the kidneys.
• Increase volume back to normal or decrease osmolarity by diluting because of that water retention.

Sensitivity

• Blood volume: Sharp increase after a 10% decrease.
• Osmotic potential: Significant increase after small changes.
• High osmotic potential outside cells (especially in the brain) draws water out of neurons, leading to cerebral edema.

Endocrine Dysregulation Examples

Low ADH: Diabetes Insipidus

• Different from diabetes mellitus (insulin).
• Large volume of tasteless (dilute) urine.
• Water isn't retained, leading to potential dehydration if water isn't freely available.

High ADH: Idiopathic ADH Syndrome

• Rare, cause unknown.
• Significant fluid retention.
• Hyponatremia (low sodium).
• Disrupts sodium-potassium pump function, affecting cell function (especially neural).
• Hypo-osmotic physiology (diluted).
• Hyponatremia related to consuming too much water which can over dilute bodily fluids.

Causes of Diabetes Insipidus

• Central: Brain tumor impacting ADH-secreting cells in the hypothalamus.
• Nephrogenic: Kidneys don't respond to ADH (genetic or downregulation of receptors).

Medications Affecting ADH Secretion

• Drugs stimulating ADH: Barbiturates, morphine, acetylcholine analogues, nicotine, pain response.
• Alcohol inhibits ADH secretion, leading to increased urination and potential dehydration.

Anterior Pituitary

General Mechanism

• Hypothalamus secretes inhibitory and releasing hormones that impact specific endocrine tissues.
• Growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH) affect growth hormone secretion from the anterior pituitary.
• A multi-layer response is seen here

Growth Hormone

• Comes from the anterior pituitary.
• Growth hormone role.
• Dysregulation of growth hormone secretion.

Hormone Specificity

• Hormones move through circulation, potentially contacting most cells.
• Not all tissues respond due to receptor presence.
• ADH works in the kidneys due to specific receptors.
• Combined effect of many hormones regulates processes.

Growth Hormone Production and Regulation

• Protein hormone (191 amino acids).
• Shared circulation between the hypothalamus and anterior pituitary.
• Hormones secreted from the hypothalamus have a direct effect on the pituitary, not peripheral tissues.
• Growth hormone is secreted in response to a balance of growth hormone inhibitory hormone and growth hormone releasing hormone.

Effects of Growth Hormone

• Maintenance of homeostasis.
• Developmental growth.
• Released in response to low blood glucose:
  • Fasting.
  • Exercise.
  • Stress.
• Diurnal changes: Sleep results in the release of growth hormone.
• High protein, low carbohydrate diets.

Hypothalamus

• Constant secretion of growth hormone releasing hormone and growth hormone inhibitory hormone with varying levels.
• Has a stimulatory and inhibitory effect on anterior pituitary.

Growth Hormone Effects

• Growth hormone effects can be direct on target tissues
• Growth hormone having effects on maintaining homeostasis.
• Growth hormone having effects on developmental growth.
• Growth Hormone can also affect the Liver and have an effect on IGF-1.
• IGF-1 will have similar effects to growth hormone.

Growth Hormone Receptor

• Interaction with the receptor stimulates various intracellular events and changes in gene expression.
• GLUT4 glucose transporter stimulated, increasing the number of glucose transporters.

Metabolic Actions

• Protein biosynthesis.
• Lipolysis.
• Inhibits tissue uptake and utilization of glucose in peripheral tissue.
• Has nutrient partitioning away from muscle.

General effects on growth:

• Stimulates the Differentiation of chondrocytes (Long bone growth).
• stimulating protein biasis and more that is stimulated through IGF-1.

Use in Animal Production

• Bovine somatotrophin (BST) in dairy production.
• Increases production (milk).
• Partitioning effect away from muscle towards mammary gland.
• Preferential nutrient partitioning towards mammary tissue, facilitating milk production.
• Slows the rate of mammary cell decrease.
• Nutrient partitioning towards the mammary gland.

Bone Growth

• Simulates bone growth, proliferation, and differentiation of cartilage cells in the epiphyseal plate.
• Bones grow longer from the epiphyseal plates.
• Growth hormone is a site that we see animal get bigger.

Dysregulation of Growth Hormones

• Type of Influence depends on when the change in regulations happens
• There can be low level levels before puberty that result in a lack of growth
• There will be excessive growth hormone before closing the epiceal plate that lead to animal that are much bigger.
• If the growth dysregulation occurs after puberty then the bones cant grow.

Post and After Puberty Influences

• Decreased availability of growth hormone has a physical affect on characteristics.