Endocrine System: Hypothalamus and Pituitary Gland

Physiology of the Pituitary Gland

• The pituitary gland (hypophysis) is a small gland (0.5-1 gm) located at the base of the brain.
• It is divided into three lobes: anterior, middle, and posterior.
• It is connected to the hypothalamus by two types of connections: vascular (hypothalamohypophyseal portal circulation) and nervous (hypothalamohypophyseal tract).

Intended Learning Objectives (ILOs)

• Students should be able to identify the hypothalamic-hypophyseal connection.
• Students should be able to identify the different parts of the pituitary gland.
• Students should be able to identify the hormones produced by each part and their functions.
• Students should be able to understand the relationship between the hypothalamus and the pituitary gland.
• Students should be able to understand the control and regulation of pituitary hormones.
• Students should be able to identify potential hormone disturbances and their management.
• Students should be able to distinguish between various short stature cases.
• Students should be able to differentiate between diabetes insipidus and diabetes mellitus.

Hypothalamic Hormones

• Growth hormone-releasing hormone (GHRH)
• Growth hormone-inhibiting hormone (GHIH)
• Corticotropin-releasing hormone (CRH)
• Thyrotropin-releasing hormone (TRH)
• Gonadotropin-releasing hormone (GnRH)
• Prolactin-releasing hormone (PRH)
• Prolactin-inhibiting hormone (PIH)

Anterior Pituitary

• Called the "master gland" as it controls other glands.
• Secretes hormones like:
  • Adrenocorticotropic hormone (ACTH)
  • Prolactin (lactogenic hormone)
  • Growth hormone (somatotropin)
  • Melanocyte-stimulating hormone (gamma form)
  • Thyroid-stimulating hormone (TSH)
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
• The intermediate lobe is rudimentary in humans, secreting alpha, beta, and gamma melanocyte-stimulating hormones.
• The posterior lobe stores and releases antidiuretic hormone (ADH) and oxytocin.

Control of Anterior Pituitary Secretion

• Controlled by the hypothalamus and feedback mechanisms.
• Hypothalamus releases hypophyseotropic hormones, secreted from the median eminence.
• These hormones reach the anterior pituitary via the hypothalamic-hypophyseal portal circulation.
• The hormones increase intracellular cAMP levels in anterior pituitary cells.

Enrichment Knowledge

• The hypothalamus connects to many brain areas, regulating bodily functions via hypothalamic hormones.
• Psychological stressors are linked to endocrine disorders.
• The hypothalamus regulates pituitary activity through releasing/inhibiting hormones.

Feedback Mechanisms

• Positive feedback: hormonal increase stimulates further hormone release from pituitary tropic or hypothalamic releasing hormones.
• Negative feedback: hormonal increase decreases the hormone's normal level; vice versa for a decrease in level.
• Mechanism occurs using two ways.

Melanocyte Stimulating Hormone (MSH)

• Crucial in skin coloration (especially in fish, reptiles, and amphibians).
• Melanin is of two types, eumelanin (black), and pheomelanin (red/yellow).
• In animals, melanophores mediate this action; in humans, melanocytes.
• Acts by increasing cAMP within target cells.

Growth Hormone

• Protein hormone similar to prolactin.
• Promotes growth promoting factor and anabolic effects.
• Increases body mass by cell division and protein synthesis.
• Increases tissue size and weight.
• Affects bone, muscle, and viscera, but not metamorphosis (which is controlled by thyroxine).
• Significant effect on cartilage growth in young animals.

Effect of Growth Hormone on Metabolism

• Increases intestinal calcium absorption, and reduces urinary excretion of sodium and potassium (electrolyte balance).
• Promotes Protein metabolism through urea and amino acids.
• Has anabolic effect, impacting the blood levels of free fatty acids and ketone bodies by mobilizing adipose tissue fatty acids and inhibiting insulin's lipogenic effect.
• Leads to a positive nitrogen balance.
• Affects carbohydrate metabolism through activating glucose-6-phosphatase enzyme.
• Increases hepatic glucose output.
• Influences glucose uptake in cells (especially skeletal muscle) by reducing tissue's insulin binding capacity and possibly reducing receptors.
• Inactivates hexokinase enzyme, preventing glucose phosphorylation.
• Raises glucose levels.

Enrichment Knowledge (Growth Hormone)

• Growth hormone increases the sensitivity of the pancreas to insulin stimuli (such as glucose and arginine).
• Thus, hormone-induced glucose increase stimulates insulin release, contributing to growth.

Somatomedins

• Polypeptide growth factors, secreted by the liver and other tissues in response to growth hormone.
• Types: IGF-I (insulin-like growth factor 1, or somatomedin C), hormone-dependent; IGF-II (insulin-like growth factor II), growth hormone-independent and possibly crucial for fetal growth.
• Growth hormone has a permissive effect on IGF-I, making target cells sensitive to IGF-I's growth-promoting actions.

Control of Growth Hormone Secretion

• Controlled by growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GHIH).
• Stimuli include energy shortage (e.g., low glucose), increased amino acid levels (e.g., arginine), exercise, stress, and sleep.
• Glucagon can also stimulate growth hormone secretion.

Follow Control of Growth Hormone Secretion

• Other hormones affecting growth include the thyroid hormone (permissive effect on growth and somatomedin potentiation), glucocorticoids (permissive effect but also catabolic action), insulin (anabolic action, critical for growth), and sex hormones (anabolic action, contributing to puberty growth).

Causes of Short Stature

• Deficient growth hormone (GH) secretion, due to pituitary or hypothalamic issues; results in infantilism if accompanied by deficient growth-stimulating hormones.
• Cretinism.
• Laron dwarfism: characterized by normal/elevated growth hormone but short stature due to somatomedin deficiency.
• Precocious puberty

Disturbance in Anterior Pituitary

• Excessive Growth Hormone
  • Gigantism (children): excessive growth hormone, before epiphyseal closure
  • Acromegaly (adults): excessive GH growth after epiphyseal closure.
• Deficient Growth Hormone
  • Pituitary dwarfism
  • Pituitary infantilism
  • Pituitary hypofunction: Partial or complete insufficiency of pituitary secretion
  • Panhypopituitarism (Simmond's disease).

Gigantism

• Etiology: excessive growth of growth hormone before epiphyseal closure in children.
• Characterized by:
  • Abnormal height
  • Large hands and feet
  • Coarse facial features (thick lips, macroglossia)
  • Breast enlargement (bilateral gynecomastia)
  • Reduced libido/impotence
  • Hyperglycemia leading to diabetes mellitus

Findings of Gigantism

• Features due to tumour mass include:
  • Headache
  • Visual field defects
  • Cranial nerve palsies
  • Enlarged pituitary fossa (detected radiographically)

Acromegaly

• Overgrowth of viscera, soft tissues (lips, nose, forehead, scalp).
• Thickened/wrinkled skin (bulldog scalp).
• Hair growth increase (hirsutism).
• 25% patient with diabetes due to diabetogenic effect of GH.
• Gynecomastia (breast enlargement in males).
• Can affect gonads leading to decreased function.
• Neurological symptoms: changes in visual field, headache, blurring vision, and vomiting

Deficient Secretion of GH (Pituitary Dwarfism)

• Characterized by:
  • Arrested growth due to early epiphyseal fusion.
  • Stature below 120cm in adulthood.
  • Body proportions similar to children (large head).
  • Delayed soft tissue growth with tendency to obesity.
  • Reduced metabolic rate.
  • Normal/high intelligence but emotional instability.
  • Normal sexual development if GH is deficient only

Pituitary Infantilism

• GH Deficiency with GTH deficiency.
• Leads to dwarfism and lack of sexual organ development.

Partial/Complete Pituitary Insufficiency (Partial/Panhypopituitarism)

• Partial: insufficient secretion of some pituitary hormones
• Complete (Simmond's disease): generalized failure of anterior pituitary.
• Characterized by:
  • Arrest in growth
  • Hypoglycemia due to GH's insulin antagonist effect
  • Reduced thyroid activity (decreased metabolism)
  • Reduced adrenal cortex activity
  • Pallor/anemia due to ACTH/MSH deficiency
  • Decreased sexual function in males and females
  • Mental deterioration
  • Anorexia, weight loss (premature senility)

Posterior Pituitary Gland (Neurohypophysis)

• Releases ADH (vasopressin) and Oxytocin from stored hormone.
• ADH:
  • Secreted from supraoptic nucleus.
  • Increases water reabsorption in kidneys (reducing urine volume)
  • Key to water retention and concentrated urine.
  • Acts on V2 receptors in collecting tubules, increasing cyclic-AMP which leads to water reabsorption to high osmotic pressure renal medulla.
• Factors stimulating ADH release:
  • Elevated plasma osmolality (dehydration).
  • Reduced extracellular fluid volume.

Function of ADH

• The release of ADH is regulated by feedback mechanisms to maintain plasma osmolality.
• Osmoreceptors in the hypothalamus detect changes in osmolality.
• Osmolality increases—ADH release increases (e.g. dehydration).
• Reduction in ECF leads to angiotensin II production—also stimulating ADH release (e.g. hemorrhage).

Function of Oxytocin

• Secreted by paraventricular nucleus (hypothalamus).
• Stored in posterior pituitary gland.
• Acts by increasing cellular calcium.
• Milk Ejection: influences myoepithelial cells in mammary glands, leading to milk ejection
• Uterine Muscle Contraction: during pregnancy and childbirth; sensitivity dependent on estrogen and progesterone levels.
• Sperm transport (male and female).

Diabetes Insipidus

• Caused by ADH deficiency or kidney's inability to respond to ADH.
• Characterized by:
  • Polyuria (excessive urination)
  • Polydipsia (excessive thirst)
  • Loss of water-soluble vitamins in urine

Diabetes Insipidus vs Diabetes Mellitus

• Comparison of Polyuria, Polydipsia, Glycosuria, Specific Gravity, Urine Color, and Urine pH

Mechanism of Milk Ejection

• Suckling stimulates touch receptors.
• Impulses are transmitted to hypothalamus, stimulating oxytocin release from the posterior pituitary and prolactin from the anterior pituitary.
• Emotional stimuli can also trigger oxytocin release.

Control of Uterine Smooth Muscle

• Oxytocin causes uterine contractions, influenced by estrogen (increases sensitivity) and progesterone (decreases sensitivity).
• Oxytocin is crucial for pregnancy maintenance and labor induction.

Test your knowledge on the connection between the hypothalamus and the pituitary gland with this quiz. Explore important functions, hormones, and feedback mechanisms related to the endocrine system. Perfect for students studying anatomy, physiology, or endocrinology.