Hormone Mechanisms and Effects

• Lecture introduces the endocrine system and examines its function in physiological process communication and control.

The Endocrine System

• Organs and tissues secrete hormones; these include the hypothalamus, pituitary, pineal, thyroid, parathyroid, thymus, heart, kidney, adipose tissue, digestive tract, adrenal gland, pancreatic islets, and the gonads(testes and ovaries).

Need for Control - Individual Cell

• Life consists of interacting biochemical reactions.
• Roche Biochemical Pathways lists 1175 structures and 1545 transformations.
• A liver cell contains around 10,000 protein types, many of which are control or catalyze biochemical pathways.
• Cell appearance and behavior is the combined effect of biochemical reactions.
• Affecting pathways can affect how a cell looks and behaves, which can be achieved by modifying enzyme activity to adjust to its external environment.

Need for Control - Multicellular Organisms

• Cells must influence other cells' biochemistry in short or long periods of time over small or large distances.
• Cells must maintain the extracellular environment which can be done through direct or indirect contribution to ECF.
• Control is exerted through secreted chemicals (hormones).

Levels of Control

• Autocrine: Secreted compound affects the cell that secreted it; cytokines are an example.
• Paracrine; Secreted compound affects neighboring cells through diffusion which can be rapid but limited by distance.
• Endocrine: Hormones are made in endocrine cells and released into the bloodstream to expose all cells, but only those with suitable receptors will respond.
• Neurohormones: Hormones made in neurons are released into the bloodstream, exposing all cells, but only those with suitable receptors will respond.
• Neurotransmitters: Neurotransmitters are released from a nerve terminal into a synaptic gap in response to action potential.
• Neurotransmitters diffuse across the gap to bind to receptors on a target cell, which could be another neuron.
• Neurotransmitters provide a highly specific control that is costly in terms of wiring but allows a very rapid response across great distances.
• Pheromones: Allow organism-to-organism chemical communication and can demonstrate sensitivity across a 3 mile range( moth antenna).

Classification of Hormones

• Hormones are classified based on their chemical structure, receptor bindings and source of secretion.
• Based on chemical structure: Peptide, steorid and amino-acid derived hormones

Peptide Hormones

• Most abundant type of hormone; small peptides( oxytocin or ADH) or large molecules (protein hormones).
• Synthesized and packaged into secretory vesicles like other proteins.
• Peptide hormones are soluble in water.
• The half-life for peptide hormone is short, around several minutes. Thus, sustainable response requires continuous secretion.
• Peptide hormones trigger changes by opening/closing channels, modulating enzymes and altering gene expression.

Mechanisms of Action

• Cell surface receptors are integral membrane proteins.

Steroid Hormones

• All steroid hormones are derived from cholesterol.
• Only the adrenal cortex and gonads can convert cholesterol to active hormones.
• Steroid-secreting cells have large amounts of smooth ER.
• Steroid hormones are lipophilic and diffuse easily across the membrane.
• Steroid hormones are not soluble in plasma and other body fluids, and are mostly bound to carrier proteins.
• Binding protects steroid hormones from degradation and extends their half-life, but also inhibits their entry into target cells.
• Only unbound hormones can pass through the target cell membrane.
• Steroid hormone receptors are found within cells and steroid receptor-hormone complexes ultimately migrate to the nucleus.
• Steroid receptor-hormone complexes act as transcription factors, activating or repressing genomic effects.

Amino Acid-Derived Hormones

• Amino acid-derived hormones are made from tryptophan or tyrosine.
• Melatonin (pineal gland) and serotonin (gut mucosa) are derived from tryptophan.
• All other amino acid-based hormones (catecholamines and thyroid hormones) are derived from tyrosine.

Mechanisms of Action

• Two groups of tyrosine-derived hormones have different mechanisms of action.
• Catecholamines (epinephrine, norepinephrine and dopamine) bind to cell membrane receptors.
• Thyroid hormones behave like steroid hormones by binding to intracellular receptors.

Hypothalamus

• Part of the endocrine system located in the brain.
• Produces ADH, oxytocin, regulatory hormones
• Considered a 'master organ' in the endocrine system, especially through the hypothalamic-pituitary-axis.
• This relationship with the pituitary allows the brain to control the endocrine system.
• Controls chemical and temperature homeostasis and is influenced by the limbic system.

Pituitary Gland

• Pituitary releases nine important peptide hormones that bind to membrane receptors and use cAMP as a second messenger.
• There are two distinct parts - the neurohypophysis (posterior pituitary) and the adenohypophysis (anterior pituitary).
• The Neurohypophysis is an outgrowth of the hypothalamus.
• The adenohypophysis is derived from gut tissue.
• Pituitary is referred to as 'master gland' of endocrine system but that id misleading as the pituitary is under central nervous system control by hypothalamus, it also controls chemical process and temperature, and is influenced by the limbic system .

Hypothalamic Control of Endocrine System

• Three Methods: secretion of regulatory hormones, production of ADH and oxytocin, and control of sympathetic output to adrenal medulla.

Controlling the Anterior Lobe (Adenohypophysis)

• Hypothalamic neurones release regulatory factors into capillaries in small amounts as target cells are millimeters away to then enter blood once diluted.
• Releasing and inhibiting hormones: Hypothalamus controls anterior pituitary gland function through releasing and inhibiting hormones.
• Growth Hormone or Somatotropin: Stimulates cell growth via somatomedins or IGF and releases hypothalamic GH( growth Releasing and inhibiting).

Hormones of the Adenohypophysis

• Prolactin (stimulation of mammary glands and milk production): hypothalamic control via prolactin releasing and inhibiting factor (dopamine).
• Thyroid Stimulating Hormone: triggers release of thyroid hormones T3 and T4 which is hypothalamically controlled via Thyrotropin Releasing Hormone (TRH) promoting TSH release.
• Adrenocorticotropic Hormone: Stimulates glucocorticoid release by adrenal gland with hypothalamic control of ACTH via Corticotrophin Releasing Hormone (CRH) stimulating ACTH release.
• Follicle Stimulating Hormone: Stimulates follicle development and estrogen secretion in women, and sperm production in men.
• Leutinizing Hormone: Causes ovulation and progesterone production in women and androgen production in males.
• Hypothalamic control of FSH/LH: Gonadotropin Releasing Hormone promotes FSH and LH secretion.
• Melanocyte Stimulating Hormone: Stimulates melanin production, stimulates pineal to release melatonin
• Hypothalamic control of MSH releases Melanotrophin.
• Endorphins: endogenous peptide "opioid" neurotransmitter with analgesic effect less characterised.

Controlling Posterior Lobe (Neurohypophysis)

• Hormones are made and packaged in the cell body of the neuron, then transported down the cell and stored in the posterior pituitary.
• Hormones are released into the blood.
• The posterior lobe hormones include ADH and oxytocin.
• Neurones in supraoptic nucleus make antidiuretic hormone (ADH, vasopressin) which decreases water lost by kidneys and elevates blood pressure.
• Neurones in the paraventricular nucleus manufacture oxytocin. Oxytocin stimulates smooth muscle cells in uterus (childbirth) and contractile cells in mammary glands ('let-down' of milk). Regulation:
• Elevated T3 inhibits release of TRH and TSH.
• Low blood osmotic pressure-inhibits hypothalamic osmoreceptors via osmoreceptors
• Collecting ducts and peritubular capillary help filter water
• ADH helps releases ater into target tissues with constricting blood vessels/
• Sudoriferous - decrease water by loss of water from the prespiration.

Feedback Control of Hormone Systems

• Body systems work on the principle of negative feedback with cortisol inhibiting Ant Pit and Hypo as an Eg of : Hypo CRHO Ant Pit ACTHO Adr CrtxO cortisol
• Positive feedback exceptions are rare with childbirth being an Ex when Ve feedback restores normal level.

Thyroid

• Thyroid mass is about 30g total and gland secretes thyroid hormones and calcitonin.
• T3, T4
• Follicle-like in cell structure
• Normal = 30g in mass and creates

Thyroid Hormones on Cells

• Free hormones diffuse into cells by binding to intracellular receptors, exerting effects on gene transcription.
• Overall basal metabolic rate and temperature effects occur, as well as growth and development.
• Follicles act as a store, bound circulating hormone acts as a store and changes in protein synthesis persist.
• Thyroid hormones stimulate the respiratory centers, leading to increased oxygenation because of increased perfusion.
• Causes increases of gene expression NA/K which leads to oximisation and increased rate of body temperature and stimulates of protiens.

Control of Thyroid Hormone Secretion

• Low blood levels stimulate release with TRH and H , T stimulates rlelase and

Adrenal Glands

• Are vital in times of stress.
• Adrenal cortex: Manufactures steroid hormones (corticosteroids)
• Adrenal medulla: release of epinephrine (75%) and norepinephrine (25%)
• Adrenal cortex has has 3 layers including G which deals.

Adrenal Cortex & Salt/Water Balance

• Produces mineralocorticoids, mainly aldosterone which releases to help with controlled and part of the Renin-Angiotensin System (RAS) Defense of Blood Pressure” with includes kidney and brain help.

Diuretic Hormone

• Antidiuretic hormone decreases urine production and controls body water involving kidneys and the vascular system.
• Kidneys return water by increase ADH by at least 10 hold!
• High fluid volume increases hypothalamus.

Regulation of ADH:

• High volume stimulated hypothalamus and the opposite decrease volume-inhibit stimulation

Autonomous Glands - Pancreas

• Contains mixed exocrine (99%)/endocrine( 1%) gland with clusters of endocrine- cells: Islets of Langerhans or pancreatic islets Alpha cells secrete glucagon and Beta cells secrete insulin.
• Consists of the exocrine and endocrine cells
• Beta cells secrete insulin
• Delta cells secrete GH-IH ( somatostatin)
• F cells secrete pancreatic polypeptide
• Islets of Langerhans control with hormones of glucagon and secretion through cells.
• Delta: somaticine = stop creating insulin and blood volume
• Beta. increase insulin and blood volume but low cells is

Insulin and Glucagon:

• Insulin: 2-chain 51polypeptide to lower blood glucose by increasing the rate of glucose utilization.
• Glucagon: 1-chain 29 aa polypeptide to increase blood glucose by increasing the rates of glycogen breakdown and glucose manufacture by the liver.
• Glucose decreases the cell and increases stimulation to relerase the
• Levels rises to decline which is not the insulin stimulation
• Break down glycogen to stimulate release.
• Insulin helps increases cell by stimulating for to occur.

Insulin's mechanism, Action, and effects

• Insulin lowers glucose and lowers blood in by 4 increase and stimulate
• This causes the the fat sythesis to create a lot of Glucose.