Endocrinology - Hypothalamus and Pituitary Gland

The Encoding System

Hypothalamus

• Connects the nervous system and the endocrine system.
• Located:
  • Inferior to the thalamus in the brain.
  • Superior to the pituitary gland.
• Connected to the pituitary gland by a structure called the infundibulum.

Regulation through the Hypothalamus

Hypothalamic Neurons

• Synthesize two hormones:
  • Antidiuretic hormone (ADH)
  • Oxytocin (OXT)
• The hypothalamus secretes regulatory hormones.
• Contains autonomic centers that exert direct neural control over the endocrine cells of the adrenal medulla.

Hormonal Interactions

• ADH and OXT are released into circulation.
• Preganglionic motor fibers direct the secretion of epinephrine (E) and norepinephrine (NE) from the adrenal medulla.

Functions of the Hypothalamus

• Links the nervous and endocrine systems.
• Synthesizes the hormones ADH and OXT which are transported to the posterior pituitary via neurons in the infundibulum.
  • ADH is synthesized in the supraoptic nuclei.
  • OXT is synthesized in the paraventricular nuclei.
• Secretes regulatory hormones that control endocrine activity of the anterior pituitary.
  • These hormones are transported via the hypophyseal portal system.
• Uses direct neural control through autonomic centers.
  • Direct sympathetic signals are sent to cells of the adrenal medulla, causing the immediate release of epinephrine and norepinephrine.

Regulatory Hormone Production

Median Eminence

• Hypothalamic neurons secrete regulatory factors into interstitial fluid.
• These factors enter the blood due to the “fenestrated” nature of capillaries in this region.
• Hypophyseal Portal System:
  • A capillary network that allows regulatory hormones to travel directly to the anterior pituitary.
  • It enables one-way communication.
  • Hormones released downstream must travel through this pathway.

Types of Regulatory Hormones

• Releasing Hormones (RH):
  • Stimulate synthesis and secretion of hormones.
• Inhibiting Hormones (IH):
  • Prevent synthesis or secretion of hormones.
• Note: There may be RH or IH or both for any given hormone.

Review Questions

1. Define regulatory hormones.
2. Identify three mechanisms by which the hypothalamus integrates the nervous and endocrine systems.
3. Describe the characteristics and functions of blood vessels linking the hypothalamus with the anterior lobe of the pituitary gland, including type of capillaries and system name.
4. Which hypothalamic nuclei synthesize ADH? Which synthesize OXT?

Pituitary Gland Anatomy

Structure

• Composed of:
  • Anterior pituitary (adenohypophysis)
  • Posterior pituitary (neurohypophysis)
  • Pars intermedia
• Location:
  • Lies in the sella turcica of the sphenoid bone.
• All hormones released here are peptide hormones.
• Hormones of anterior lobe are all tropic hormones, meaning they activate or support other endocrine glands.

Hormones of the Anterior Pituitary

Growth Hormone (GH)

• Known as somatotropin.
• Primary control mechanism is indirect.
• Liver cells respond to GH by synthesizing and releasing somatomedins (insulin-like growth factors).
• Somatomedins stimulate growth by increasing uptake of amino acids.
• Direct actions of GH include:
  • Stimulating cell division in epithelia and connective tissues.
  • Stimulating triglyceride breakdown in adipose tissue.
  • Producing a glucose-sparing effect, switching preparations from glucose to fatty acids for ATP production.
  • Stimulating glycogen breakdown in the liver.

Posterior Pituitary (Neurohypophysis)

• Contains axons of hypothalamic neurons.
• Releases two hormones produced in the hypothalamus:
  • ADH (vasopressin)
  • Target: Kidneys.
  • Released in response to increased solute concentration in blood or decreased blood volume/pressure.
  • Alcohol inhibits ADH release.
  • OXT:
  • Target: Uterine wall (specific target in males is uncertain).
  • Stimulates smooth muscle contraction, promoting labor and delivery.
• The pathways involve both neural and endocrine mechanisms, termed “neuroendocrine response”.
• The release of epinephrine and norepinephrine is another example.

Negative Feedback Mechanism

• Most common hormone control mechanism.
• Sequence of events:
  • Hypothalamus secretes releasing hormones into the anterior pituitary.
  • Anterior pituitary releases hormone #1 to another endocrine organ.
  • That organ then releases hormone #2 which travels to the target.
  • Example sequences include:
  • TRH → TSH → Thyroid → T3/T4
  • CRH → ACTH → Adrenal cortex → Glucocorticoids
  • GnRH → FSH → Testes/Ovaries → Inhibin
  • GnRH → LH → Testes/Ovaries → Androgens/Estrogen

Regulation of GH and PRL

• GH and PRL utilize both releasing and inhibiting hormones for regulation.
  • Example for GH regulation:
  • GHRH → GH → Liver → Somatomedins
  • Somatomedins inhibit GHRH.
  • Somatomedins stimulate GHIH.
  • Example for PRL regulation:
  • PRH → PRL
  • PRL inhibits PRH.

Thyroid Gland

Anatomy

• Located on:
  • Anterior surface of the trachea.
  • Inferior to the thyroid cartilage (laryngeal prominence or “adam’s apple”).
• Structure:
  • Composed of two lobes connected by an isthmus.
  • Extensive blood supply.

Thyroid Histology

Structure of Thyroid Follicles

• Composed of:
  • Viscous colloid surrounded by simple cuboidal epithelial cells.
  • Capillary network surrounding each follicle.
• Follicle cells secrete thyroglobulin into the colloid, which contains tyrosine (the building block of thyroid hormones).
• Parafollicular cells:
  • Also known as clear cells or C-cells.
  • Found between follicles and produce calcitonin (which helps regulate calcium levels in body fluids).

Thyroid Hormone Production

Steps in Production

1. Iodide ions absorbed from the diet are transported to the thyroid gland via blood and then into the cytoplasm of follicle cells using carrier proteins.
2. Thyroid-oxidase, an enzyme in follicle cells, converts iodide ions to iodine by removing one electron and attaches one or two iodine atoms to the tyrosine in thyroglobulin within the follicle cavity.
3. Tyrosine molecules with attached iodine atoms become linked, forming thyroid hormone molecules that remain in the thyroglobulin.
4. Follicle cells remove thyroglobulin via endocytosis.
5. Lysosomal enzymes break down thyroglobulin, recycling amino acids to synthesize more thyroglobulin. Hormones enter the cytoplasm of follicle cells.
6. T3 (triiodothyronine) and T4 (thyroxine) diffuse across the basement membrane into the blood, with 90% being T4, even though T3 has a much stronger metabolic effect.
7. About 75% of T4 and 70% of T3 are bound to transport proteins known as thyroid-binding globulins (TBGs), allowing them to remain in circulation longer.

Effects of Thyroid Hormones

• Increased rate of oxygen and energy consumption, potentially causing an increase in body temperature in children.
• Increased heart rate and force of contraction, generally with an associated increase in blood pressure.
• Increased sensitivity to sympathetic stimulation.
• Maintenance of normal sensitivity of respiratory centers to variations in oxygen and carbon dioxide concentrations.
• Stimulation of red blood cell (RBC) formation, enhancing oxygen delivery.
• Stimulation of activity in other endocrine tissues.
• Accelerated turnover of minerals in bone.

Parathyroid Glands

Anatomy

• Composed of two pairs of glands embedded on the posterior surface of the thyroid gland.
• Contains two cell types:
  • Parathyroid cells (or principal cells): Produce parathyroid hormone (PTH).
  • Oxyphil cells: Function is unknown.

Regulation of Calcium Levels

• When blood calcium levels fall, parathyroid cells secrete PTH which results in an increase in calcium levels.
• PTH and calcitonin have opposing effects on calcium levels in the body.
• In healthy adults, PTH and calcitriol primarily regulate calcium homeostasis.

Calcium Homeostasis Mechanism

• Homeostasis Disturbance:

  • Increased blood calcium level.
  • Stimulus: Receptors detect elevated levels leading to secretion of calcitonin from the thyroid gland.
  • Effectors (kidneys, digestive tract) respond to decrease calcium excretion and absorption, restoring homeostasis.

• Homeostasis Disturbance:

  • Decreased blood calcium level.
  • Stimulus: Receptors in parathyroid glands detect low levels leading to PTH secretion.
  • Effectors (kidneys, bone, digestive tract) respond to increase calcium reabsorption by kidneys, release calcium from bone, and increase calcitriol production to absorb calcium in the digestive tract, thus restoring homeostasis.

Mechanism of PTH on Blood Calcium Levels

• Skeletal System: PTH stimulates osteoblasts to secrete RANKL, which increases osteoclast activity, causing the breakdown of bone matrix, thus raising blood calcium levels.
• Urinary System: PTH increases calcium reabsorption in kidneys reducing urinary loss. It stimulates the production of calcitriol by kidneys.
• Digestive System: Increased secretion of calcitriol from glands stimulates calcium absorption from the digestive tract.

Adrenal Glands

Anatomy

• Known as suprarenal glands.
• Located on the superior border of each kidney.
• Positioned retroperitoneally (behind the peritoneum).
• Composed of three parts:
  • Adrenal Capsule: The outer covering.
  • Adrenal Cortex:
  • Yellowish outer region high in lipids (cholesterol & fatty acids).
  • Produces corticosteroids.
  • Comprised of three layers (zones).
  • Adrenal Medulla:
  • Central region that synthesizes epinephrine and norepinephrine.