BIO2305 Endocrine System

Brief Review of Endocrine vs Nervous System

  • Nervous system performs short term crisis management
  • Controls and coordinates bodily activities that require rapid responses
  • Endocrine system regulates long term ongoing metabolic activity management
  • Endocrine communication is carried out by endocrine cells that release hormones in order to alter metabolic activities

Endocrine System Functions

  • “Endo-” = within “-crine” = to secrete (Greek)
  • Endocrine System - the system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body
  • Endocrine System functions include:
  • Maintenance of an optimum biochemical environment within the body
  • Influences metabolic activities
  • Integration and regulation of growth and development
  • Control, maintenance, and instigation of sexual reproduction

Endocrine System: Overview

  • Endocrine glands:
  • hypothalamus
  • pituitary (adenohypophysis)
  • pineal
  • thyroid
  • parathyroid
  • thymus
  • adrenal
  • pancreas
  • gonads
  • The hypothalamus has both neural and endocrine functions
  • The pancreas and gonads produce both hormones and exocrine products
  • Other tissues and organs that produce hormones – adipose cells, cells of the small intestine, stomach, kidneys, and heart

The Endocrine System

Hormones

  • “Hormone” = from Greek hormao = to excite, arouse, spur
  • Hormones – chemicals secreted by cells into the bloodstream for transport to distant target tissues
  • Regulate the metabolic function of other cells
  • Have lag times ranging from seconds to hours
  • Tend to have prolonged effects
  • Produce effects at very low concentrations
  • Are classified as amino acid-based hormones, or steroids
  • Ultimate Goal: to generate a cellular response, regardless of method
  • Cellular Response - binding of chemical signals (ie: hormones) to their corresponding receptors to induce events within the cell that ultimately change its behavior

Mechanism of Hormone Action

  • Hormones produce one or more of the following cellular changes in target cells:
  • Alter plasma membrane permeability
  • Stimulate gene activation & protein synthesis
  • Activate or deactivate enzyme systems
  • Induce secretory activity
  • Stimulate mitosis & cytokinesis
  • Free vs Bound Hormones:
  • Most endocrine systems monitor [free hormone] only
  • Increasing binding proteins in blood (carrier proteins, eg: T4-binding globulin or albumin), lowers certain hormones’ effective circulating concentration


Hormones Are Ligands

  • Ligand – in biochemistry, anything that binds to a protein receptor
  • Examples:
  • Ions
  • Hormones
  • Neurotransmitters
  • Drugs
  • Toxins
  • Gases
  • Receptor – a cellular protein that binds to a ligand; used to continually monitor changes in the internal or external environment
  • Types:
  • Membrane Receptor – embedded in the membrane, with receptor site facing outward
  • G-protein
  • Ligand gated channel
  • Cytosolic Receptor – located within the cell’s cytoplasm
  • Nuclear Receptor – located within the cell’s nucleus

Classification of Hormones based on chemical composition

  • Hormones can be classified based on chemical composition:
  • Amino Acid Derivatives
  • Tyrosine Based – Catecholamines (Epi, NE, Dopa) & Thyroid hormones
  • Tryptophan Based – Serotonin & Melatonin
  • Protein Derivatives (most hormones belong to this class)
  • Glycoproteins – carbohydrate + protein
  • Short Polypeptides – less than 200 amino acids
  • Lipid Derivatives
  • Steroids – gonadal and adrenocortical hormones
  • Eicosanoids – lipid based hormones that act locally on the same cell that released it or nearby cells (autocrine and paracrine mediators)


Classification of Hormones

Hormone Action

  • Amino Acid Derivatives
  • Tyrosine Based
  • Catecholamines
  • Bind to membrane receptors
  • Activate 2nd messenger systems
  • Thyroid Hormones
  • Diffuse through membrane
  • Activate genes for protein synthesis
  • Tryptophan Based
  • Serotonin, Melatonin
  • Bind to membrane receptors
  • Activate both ligand-gated ion channels and G protein-coupled receptors
  • Protein Derivatives
  • Glycoproteins & Short Polypeptides
  • Diffuse through membrane
  • Activate genes for protein synthesis and activate existing proteins
  • Lipid Derivatives
  • Steroids & Eicosanoids
  • Bind to membrane receptors or diffuse through membrane
  • Activate 2nd messenger systems and genes for protein synthesis
  • *Remember, just because a substance is lipophilic does not necessarily mean all receptors are intracellular; some are membrane-bound*

Classification of Hormones based on receptors

  • Hormones can also be classified based on location of receptors:
  • Membrane Receptors
  • Second messengers systems (G protein-linked)
  • Tyrosine kinase-linked receptors
  • Hormone-gated ion channels
  • Intracellular and intranuclear receptors
  • Most amino acid based-hormones use G protein-linked receptors for signal transduction
  • Most steroid hormones can diffuse through the membrane and, therefore, bind to receptors found in the cytosol and nucleus, with the goal of activating or repressing genes

AA-Based Hormone Action: cAMP-2nd Messenger


AA-Based Hormone Action: PIP2-Calcium

G Proteins and Hormone Activity

Steroid Hormones

  • Steroid hormones diffuse into target cells to bind and activate a specific intracellular receptor
  • Cytosolic hormone-receptor complex (Type I NR)
  • travels to the nucleus
  • binds to a DNA-associated receptor protein
  • prompts DNA transcription & protein synthesis
  • Nuclear hormone-receptor complex (Type II NR)
  • located within nucleus at DNA-associated receptor protein
  • prompts DNA transcription & protein synthesis


Steroid Hormones

Target Cell Specificity

  • Hormones circulate to all tissues but only activate target cells
  • Target cells must have specific receptors to which the hormone binds
  • These receptors may be intracellular or located on the plasma membrane
  • Examples of hormone activity:
  • ACTH receptors are only found on certain cells of the adrenal cortex
  • Thyroxin receptors are found on nearly all cells of the body

Target Cell Activation

  • Target cell activation depends on three factors
  • Blood levels of the hormone
  • Relative number of receptors on the target cell
  • The affinity of those receptors for the hormone
  • Up-regulation – target cells form more receptors in response to the hormone
  • Down-regulation – target cells lose receptors in response to the hormone

Hormone Concentrations in the Blood

  • Hormones circulate in the blood in two forms – free or bound
  • Hormones bound to plasma proteins:
  • Steroids (corticoids)
  • T3 T4
  • GH
  • oxytocin & vasopressin
  • Almost all others are unencumbered
  • Concentrations of circulating hormone reflect:
  • Rate of release
  • Speed of inactivation and removal from the body
  • Hormones are removed from the blood by:
  • Degrading enzymes
  • Kidney filtration
  • Liver enzymes

Interaction of Hormones

  • Three types of hormone interaction
  • Permissiveness – one hormone cannot exert its effects without another hormone being present
  • Synergism – more than one hormone produces the same effects on a target cell
  • Antagonism – one or more hormones opposes the action of another hormone

Control of Hormone Release

  • Blood levels of hormones:
  • Are controlled by negative feedback systems
  • Vary only within a narrow desirable range
  • Hormones are synthesized and released in response to humoral, hormonal, and neural stimuli

Humoral Stimuli

  • Hormone secretion initiated by Humoral Stimuli
  • Humoral = of body fluids (ie: blood)
  • Secretion of hormones in direct response to changing blood levels of ions, nutrients, and gases
  • Example: [Ca2+] in the blood
  • ↓ [Ca2+] in blood stimulates parathyroid glands to secrete PTH (parathyroid hormone)
  • ↑ PTH causes [Ca2+] in blood to rise (Ca2+ is reabsorbed in kidneys and leached from bones) and the stimulus is removed

Hormonal Stimuli

  • Hormone secretion initiated by Hormonal Stimuli
  • Hormones are released in response to hormones produced by other endocrine organs
  • Hypothalamic “releasing-hormones” stimulate the anterior pituitary to release hormones
  • Anterior pituitary’s tropic hormones stimulate target glands to secrete still more hormones
  • Tropic vs. Trophic:
  • Tropic – describing a hormone that stimulates release of another hormone
  • Trophic – describing a hormone that stimulates growth and nourishment of a gland (increasing hormone release by that gland)
  • ACTH is tropic and trophic. It causes release of cortisol from the adrenal gland (tropic), and stimulates the growth of the adrenal gland (trophic)

Neural Stimuli

  • Hormone secretion initiated by Neural Stimuli
  • Hormones are released in response to neural stimulation originating from the CNS (brain, spinal cord)
  • Action potential travels along sympathetic nerve fibers that synapse at the adrenal medulla
  • Chromaffin cells respond by releasing hormones (catecholamines such as EPI and NE) into the blood.

Endocrine Control: Three Levels of Integration

  • Hypothalamic stimulation from CNS
  • Pituitary stimulation from hypothalamic tropic hormones
  • Endocrine gland stimulation–from pituitary tropic hormones

Feedback Control of Endocrine Secretion

Hormonal NFbL - Hypothalamic-Pituitary-Thyroid axis (HPT Axis)


Hormonal NFbL - Hypothalamic-Pituitary-Adrenal axis (HPA Axis)

Neural Stimulation

  • ANS efferent nerve fibers stimulate hormone release
  • The preganglionic fiber from the CNS passes through, but does not synapse at, the sympathetic chain ganglion. It continues to the adrenal medulla where it synapses with medullary glandular cells
  • The preganglionic sympathetic nerve fibers stimulate the chromaffin cells within the adrenal medulla to secrete catecholamines (Epi, NE) into the bloodstream
  • Chromaffin cells – modified postganglionic sympathetic neurons within the adrenal medulla that secrete epinephrine and norepinephrine
  • Chromaffin cells use the enzyme dopamine β-hydroxylase to convert of dopamine to noradrenalie

Nervous System Modulation

  • The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms
  • The nervous system can override normal endocrine controls
  • Example: Neural control of blood glucose levels (BGL)
  • BGL normally maintained by endocrine system
  • However, under stress, the body needs more glucose
  • The hypothalamus and the sympathetic nervous system are overridden by cerebral cortex and limbic system to supply ample glucose
  • How?
  • Cerebral cortex and limbic system stimulate hypothalamus to release CRH
  • Adenohypophysis releases ACTH into blood
  • Adrenal cortex releases Cortisol
  • Cortisol stimulates gluconeogenesis
  • ↑ Blood glucose level (BGL)

Overview of Major Endocrine Organs and Hormones

  • Hypothalamus
  • Thyrotropin-releasing hormone (TRH)
  • Prolactin Inhibiting Hormone/Dopamine (PIH)
  • Growth hormone-releasing hormone (GHRH)
  • Growth hormone-inhibiting hormone/Somatostatin (GHIH)
  • Corticotropin-releasing hormone (CRH)
  • Gonadotropin-releasing hormone (GnRH)
  • Neurohypophysis

(synthesized by Hypothalamus)

  • Oxytocin
  • Vasopressin (ADH)
  • Adenohypophysis
  • Thyroid-stimulating hormone (TSH)
  • Prolactin (PRL)
  • Growth hormone (GH)
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Infundibulum
  • Melanocyte–stimulating hormones (MSHs)


Major Endocrine Organs

  • The hypothalamus sends releasing hormones to the adenohypophysis and neural stimuli to the neurohypophysis
  • Hypothalamus > Adenohypohysis:
  • Thyrotropin releasing hormone (TRH) > release of TSH and PRL
  • Prolactin inhibiting hormone (PIH) > inhibits release of PRL
  • Growth hormone-releasing hormone (GHRH) > release of GH
  • Growth hormone-inhibiting hormone (GHIH) > inhibits release of GH
  • Corticotropin releasing hormone (CRH) > release of ACTH
  • Gonadotropin releasing hormone (GnRH) > release of FSH and LH
  • Hypothalamus > Neurohypophysis
  • Action potential > ADH
  • Action potential > Oxytocin
  • Pituitary gland – bilobed organ that secretes

nine major hormones, all use cAMP 2nd messenger system

  • Neurohypophysis
  • posterior lobe, made up of neural tissue
  • receives, stores, and releases hormones from the hypothalamus
  • Adenohypophysis
  • anterior lobe, made up of glandular tissue
  • synthesizes and secretes a number of hormones
  • Infundibulum
  • the pituitary stalk connecting the hypothalamus to the neurohypophysis
  • synthesizes and releases Melanocyte–stimulating hormones (MSHs)

which stimulate production and release of melanin by melanocytes in skin and hair


Hypophysis (Pituitary Gland)

  • Pituitary Gland – bilobed organ that secretes nine major hormones, all use cAMP 2nd messenger system
  • Neurohypophysis stores and releases two hormones from hypothalamus
  • Oxytocin and antidiuretic hormone (ADH)
  • These hormones are transported in vesicles from hypothalamus to the neurohypophysis for release
  • Adenohypophysis synthesizes and releases six hormones:
  • Are abbreviated as TSH, PRL, GH, ACTH, FSH, and LH
  • Regulate the activity of other endocrine glands

Anterior Lobe of the Pituitary Gland (Adenohypophysis)

  • Adenohypophysis - anterior lobe of pituitary gland
  • made of glandular tissue
  • synthesizes and secretes six hormones
  • Six Hormones of the Adenohypophysis:
  • Thyroid-stimulating hormone (TSH)
  • Prolactin (PH or PRL)
  • Growth hormone (GH)
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)

Growth Hormone (GH)

  • Produced by somatotropic cells of the anterior lobe
  • Function:
  • GH stimulates liver, skeletal muscle, bone, and cartilage to release insulin-like growth factors (IGFs)
  • GH increases cell metabolism and blood glucose level
  • Promotes use of fats for fuel (lipolysis & gluconeogenesis) and protein synthesis
  • Most effects are mediated indirectly by somatomedins
  • Hypothalamic hormones regulate GH
  • Growth hormone–releasing hormone (GHRH) stimulates GH release
  • Growth hormone–inhibiting hormone (GHIH) inhibits GH release

Metabolic Action of Growth Hormone

Thyroid Stimulating Hormone (TSH)

  • Tropic hormone that stimulates the normal development and secretory activity of the thyroid gland
  • Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH)
  • Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH

Adrenocorticotropic Hormone (ACTH)

  • Stimulates the adrenal cortex to release corticosteroids
  • Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm
  • Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH

Gonadotropins - FSH, LH

  • Gonadotropin Functions:
  • Regulate the function of the ovaries and testes
  • Triggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after puberty
  • Two Gonadotropins:
  • Follicle-stimulating hormone (FSH)
  • FSH stimulates gamete (egg or sperm) production
  • Luteinizing hormone (LH)
  • LH In females:
  • LH works with FSH to cause maturation of the ovarian follicle
  • LH works alone to trigger ovulation (expulsion of the egg from the follicle)
  • LH promotes synthesis and release of estrogens and progesterone
  • LH in males:
  • LH stimulates interstitial cells of the testes to produce testosterone
  • LH is also referred to as interstitial cell-stimulating hormone (ICSH)

Prolactin

  • In females, stimulates milk production by the breasts
  • Triggered by the hypothalamic prolactin-releasing hormone (PRH)
  • Inhibited by prolactin-inhibiting hormone (PIH)
  • Blood levels rise toward the end of pregnancy
  • Suckling stimulates PRH release and encourages continued milk production


Neurohormones: secreted into the blood by neurons

  • Neurocrine – any molecules secreted by a neuron
  • Neurohormone – a neurocrine hormone that is produced and secreted by a neuron into the blood, targeting distant cells (ie: ADH, oxytocin)

Contrast Neurohormones with other Neurocrines:

  • Neuromodulator – slow acting paracrine chemicals that alter the response of a neuron more slowly than nerotransmitters; usually found in circulating in CSF
  • Neurotransmitter – a fast paracrine chemical signal released by a neuron that influences the neuron’s target cell immediately

Posterior Lobe of the Pituitary Gland (Neurohypophysis)

  • Neurohypophysis –
  • Posterior lobe of pituitary gland
  • Made of axons of hypothalamic nerves
  • Neurons of the supraoptic nucleus manufacture antidiuretic hormone (vasopressin)
  • Decreases the amount of water lost at the kidneys
  • Elevates blood pressure
  • Neurons of the paraventricular nucleus manufacture oxytocin
  • Stimulates contractile cells in mammary glands
  • Stimulates smooth muscle cells in uterus

Oxytocin

  • Oxytocin is a strong stimulant of uterine contraction
  • Regulated by a positive feedback mechanism to oxytocin in the blood
  • This leads to increased intensity of uterine contractions, ending in birth
  • Oxytocin triggers milk ejection (“letdown” reflex) in women producing milk
  • Synthetic and natural oxytocic drugs are used to induce or hasten labor
  • Plays a role in sexual arousal and satisfaction in males and non-lactating females

Antidiuretic Hormone (ADH)

  • ADH helps to avoid dehydration or water overload - prevents urine formation
  • Osmoreceptors monitor the solute concentration of the blood
  • With high solutes, ADH is synthesized and released, thus preserving water
  • With low solutes, ADH is not released, thus causing water loss from the body
  • Alcohol inhibits ADH release and causes copious urine output

Thyroid Gland