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Endocrinology: Endocrine Systems; Hormones; The Pituitary

Endocrinology

  • Endocrinology is the branch of biology dealing with the endocrine glands and their secretions (hormones), especially in relation to their processes or functions.

Endocrine Glands

  • Secrete hormones directly into the bloodstream.
  • They are ductless, unlike exocrine glands.

Hormones

  • The term "hormone" comes from the Greek word "hormaein," meaning to stimulate or excite.
  • A hormone is a substance secreted by cells in one part of the body that passes to another part where it is effective, in very small concentrations, at regulating the growth or activity of the cells.
  • Hormones function as long-term regulators of many activities, often involved in homeostasis (state of steady internal physical and chemical conditions).
    • Example: regulation of plasma calcium via hormones excreted by the parathyroid gland.
  • The level of circulating hormones will rise and fall in response to certain stimuli.
    • Example: levels of insulin increase in response to blood glucose.
  • Only cells with the appropriate receptor will respond to the hormone.

Hormone Secretion and Transport

  • Hormones are usually secreted directly into the bloodstream by the endocrine glands.
  • They are transferred to the site of action, or target organ.
  • They are usually complexed with (transported by) plasma proteins, e.g., growth hormone.
  • Some hormones are produced by neurons and are known as neurohormones (neurosecretion).
    • They pass down the axon to the nerve endings.
    • They are released into special capillary networks near the target organ.
    • Example: serotonin.

Tissue Hormones

  • Numerous other substances, often considered hormones, are produced in various parts of the body which have a local effect on cells and tissues.
  • Examples:
    • Kinins: Bradykinin (blood vessel dilation).
    • Prostaglandins: Prostaglandin H2 (inflammatory mediator).
    • Hormones of the GIT:
      • Gastrin (gastric acid secretion).
      • Secretin (regulation of pH in the duodenum).
      • Cholecystokinin (digestion of fat & protein).
    • Adipose tissue:
      • Adiponectin (glucose regulation and fatty acid catabolism).
      • Resistin (inflammation/obesity/T2DM?).

Types of Hormones (Functionality)

  • Autocrine: Local regulators.
    • Signaling molecules act on the same cells to amplify signals.
    • Example: The cytokine interleukin-1, an inflammatory cytokine which induces fever.
  • Paracrine: Local regulators.
    • Signaling molecules act on neighboring cells.
    • Example: Serotonin – helps regulate a wide range of activities including mood and social behavior, appetite and digestion, sleep, memory, and body temperature.
  • Endocrine signaling:
    • Hormones act on target cells distant from the site of synthesis.
    • Example: Adrenocorticotrophic Hormone – stimulates the release of steroids.

Classes of Endocrine Hormones

Four major chemical groups of hormones:

  1. Peptide hormones
    • Long chains of amino acids
    • Examples: vasopressin, oxytocin
  2. Amino acid derived hormones
    • Derived from amino acids (tryptophan or tyrosine)
    • Example: adrenaline
  3. Steroid hormones
    • Derivatives of cholesterol
    • Examples: testosterone, oestrogen, cortisol
  4. Fatty acid derivatives
    • Derived from arachidonic acid
    • Examples: prostaglandins

Mechanism of Action

Control the activities of the cells and tissues in the target organ.

This may be generally brought about in four ways:

  1. Influencing the rate of synthesis of enzymes or other proteins.
  2. Altering the rate of enzyme catalysis.
  3. Speeding up or slowing down metabolic pathways.
  4. Altering the permeability of the cell membrane.

Two general mechanisms are most widely utilized, depending on whether the hormone is hydrophobic or hydrophilic:

  • Intracellular signalling – hydrophobic
  • Cell-surface signalling – hydrophilic

Lipid-Soluble Hormones

  • Steroid and thyroid hormones are small, lipid-soluble molecules that pass through the plasma membrane.
  • They pass into the nucleus and interact with its receptor to activate or repress specific genes.
  • Synthesis of specific proteins leads to the changes we recognize as the hormone’s actions.

Water-Soluble Hormones

  • Water-soluble hormones (e.g., Peptide Hormones) cannot directly pass through the plasma membrane.
  • Process:
    • Hormones attach to specific receptors on the cell surface.
    • The receptor transmits this signal into the cell by different mechanisms but many are GPCRs (G-protein-coupled receptors).
    • Binding of hormone triggers conformational change in the receptor.
    • G protein becomes activated and moves away from the receptor.
    • G protein can then activate the next signaling protein in the pathway, often adenylyl cyclase.
    • ATP -- > cyclic-AMP
    • Leads to a phosphorylation cascade.
    • Alters internal activity of the cell (e.g., metabolism, membrane permeability, or gene activity).

Amino Acid Derived Hormones

  • Some are lipid soluble (e.g., Thyroid hormones) and others are water-soluble (e.g., Catecholamine like adrenaline or dopamine).
  • This is based on the polarity of the amino acids.

Hypothalamus – Pituitary - Endocrine Glands

  • Trophic = hormones that stimulate the growth and activity of other endocrine glands
  • Most regulation in these systems is via negative feedback loops

Hypothalamus

  • Neuro-Endocrine Master Regulator
  • Links the nervous system to the endocrine system.
  • Receives input from other areas of the brain and alters the release of hormones in response.
  • Secretes neurohormones.
  • Hormones synthesized in the hypothalamus will be either stored in the pituitary gland (posterior pituitary) for later secretion or regulate the production of hormones within the pituitary itself (anterior pituitary).
  • Most of the hormones generated in the hypothalamus are distributed to the pituitary via the hypothalamic-hypophyseal portal system.
  • Regulatory hormones – Inhibitory and stimulatory hormones

Pituitary Gland

  • Endocrine Master Regulator
  • Controls the other endocrine glands
  • Influenced by endocrine glands via a system of mostly negative feedback loops.
  • Partially regulated by the hypothalamus
  • Consists of two lobes derived from different embryonic tissue:
    • Posterior pituitary (neurohypophysis) is neural tissue.
    • Anterior pituitary (adenohypophysis) is glandular tissue.
  • Lies in a depression in the floor of the cranium (sella turcica) above the mouth in what is probably the most protected part of the organism.
  • In humans, it is about the size of a small cherry and weighs about 0.5 grams.
  • Attached by a short connection called the pituitary stalk to the hypothalamus.

Pituitary Gland – Embryology

  • Composed of two separate glands which are derived from two separate areas in the embryo:
    • One part is derived from a downgrowth of the hypothalamus, the infundibulum.
    • The other from Rathke’s pouch.
  • Hypothalamus extends to form:
    • Infundibulum
    • Posterior pituitary
  • Rathke’s Pouch
    • Depression of the roof of the developing mouth
    • Breaks away from the pharynx
    • Forms anterior pituitary
  • Posterior pituitary (neurohypophysis) Composed of two parts: pars nervosa and the median eminence.
  • Anterior pituitary (adenohypophysis) developed from an inpushing of the mouth ectoderm called Rathke's pouch.
  • Rathke’s pouch comes in contact with the infundibulum and eventually constricts off from the mouth forming a cavity of its own.
  • This constricts in the middle to form two lobes which grow out to surround the infundibular neck forming the pars tuberalis
  • The pars intermedia is formed from that part of the pouch which met the infundibulum first
  • The remainder forms the pars distalis or Anterior Lobe
  • The pars distalis and pars intermedia are separated by the remains of Rathke's pouch called the residual cleft

Pituitary Gland – Function

  • Seven major hormones are secreted by the anterior pituitary, four of which are tropic hormones
    • Tropic hormones = have another endocrine gland as the target organ
  • Most anterior pituitary hormones have both releasing and inhibitory factors
    • The releasing function is dominant
    • Prolactin is an exception; inhibited by dopamine

Anterior Pituitary Hormone:

  • Growth Hormone
  • Prolactin
  • Follicle-stimulating Hormone
  • Luteinizing Hormone
  • Thyroid-stimulating Hormone
  • Adrenocorticotrophic hormone
  • Endorphins

Hypothalamic Hormone:

  • Growth hormone releasing hormone
  • Dopamine (inhibition)
  • Gonadotrophin-releasing hormone
  • Gonadotrophin-releasing hormone
  • Thyrotrophin-releasing hormone
  • Corticotrophin-releasing hormone

Pituitary Gland – Regulation

Hypothalamus-pituitary axis

  • The control and secretion of pituitary hormones is under the direction of the hypothalamus which releases special neurohormones
  • These are called Hypothalamic Releasing and Hypothalamic Inhibitory Hormones
  • The hypothalamus is divided into areas or nuclei which release specific hormones
    • Example: Paraventricular and supraoptic nuclei release oxytocin and vasopressin to pars nervosa
    • Tuberal nuclei (e.g., arcuate) releases luteinizing hormone and follicle-stimulating hormone releasing factor to pars distalis
  • The final hormones ultimately inhibit the pituitary gland and the hypothalamus (negative feedback loops)