Endocrine System part two

Endocrine System: Overview

•      Endocrine system –  the body’s second great controlling system which influences metabolic activities of cells by means of hormones

•      Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus glands

•      The pancreas and gonads produce both hormones and exocrine products

•      The hypothalamus has both neural functions and releases hormones

•      Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart

Hormones

•      Hormones – chemical substances secreted by cells into the extracellular fluids

•    Regulate the metabolic function of other cells

•    Have lag times ranging from seconds to hours

•    Tend to have prolonged effects

•    Are classified as amino acid-based hormones, or steroids

•      Eicosanoids – biologically active lipids with local hormone–like activity

Types of Hormones

•      Amino acid–based – most hormones belong to this class, including:

•    Amines, thyroxine, peptide, and protein hormones

•      Steroids – gonadal and adrenocoritcal hormones

•      Eicosanoids – leukotrienes and prostaglandins

Hormone Action

•      Hormones alter cell activity by one of two mechanisms

•    Second messengers involving:

•   Regulatory G proteins

•   Amino acid–based hormones

•    Direct gene activation involving steroid hormones

•      The precise response depends on the type of the target cell

Mechanism of Hormone Action

•      Hormones produce one or more of the following cellular changes:

•    Alter plasma membrane permeability

•    Stimulate protein synthesis

•    Activate or deactivate enzyme systems

•    Induce secretory activity

•    Stimulate mitosis

Amino Acid–Based Hormone Action: cAMP Second Messenger

•      Hormone (first messenger) binds to its receptor, which then binds to a G protein

•      The G protein is then activated as it binds GTP, displacing GDP

•      Activated G protein activates the effector enzyme adenylate cyclase

•      Adenylate cyclase generates cAMP (second messenger ) from ATP

•      cAMP activates protein kinases, which then cause cellular effects

Amino Acid–Based Hormone Action:
PIP-Calcium

•      Hormone binds to the receptor and activates G protein

•      G protein binds and activates a phospholipase enzyme

•      Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers)

•      DAG activates protein kinases; IP3 triggers release of Ca2+ stores

•      Ca2+ (third messenger) alters cellular responses

Amino Acid–Based Hormone Action:
PIP-Calcium

Steroid Hormones

•      Steroid hormones and thyroid hormone diffuse easily into their target cells

•      Once inside, they bind and activate a specific intracellular receptor

•      The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein

•      This interaction prompts DNA transcription, to producing mRNA

•      The mRNA is translated into proteins, which bring about a cellular effect

Steroid Hormones

Hormone–Target Cell Specificity

•      Hormones circulate to all tissues but only activate cells referred to as 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 upon 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

•      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

•    The kidneys

•    Liver enzyme systems

Control of Hormone Synthesis and 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 stimuli

•    Neural stimuli

•    Hormonal stimuli

Humoral Stimuli

•      Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients

•      Example: concentration of calcium ions in the blood

•    Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)

•    PTH causes Ca2+ concentrations to rise and the stimulus is removed

Neural Stimuli

•      Neural stimuli – nerve fibers stimulate hormone release

•    Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines

Hormonal Stimuli

•      Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs

•    The hypothalamic hormones stimulate the anterior pituitary

•    In turn, pituitary hormones stimulate targets to secrete still more hormones

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

•    For example, control of blood glucose levels

•   Normally the endocrine system maintains blood glucose

•   Under stress, the body needs more glucose

•   The hypothalamus and the sympathetic nervous system are activated to supply ample glucose

Location of the Major Endocrine Glands

•      The major endocrine glands include:

•    Pineal gland, hypothalamus, and pituitary

•    Thyroid, parathyroid, and thymus

•    Adrenal glands and pancreas

•    Gonads – male testes and female ovaries

Major Endocrine Organs: Pituitary (Hypophysis)

•      Pituitary gland – two-lobed organ that secretes nine major hormones

•      Neurohypophysis – posterior lobe (neural tissue) and the infundibulum

•    Receives, stores, and releases hormones from the hypothalamus

•      Adenohypophysis – anterior lobe, made up of glandular tissue

•    Synthesizes and secretes a number of hormones

Pituitary-Hypothalamic Relationships: Posterior Lobe

•      Posterior lobe – a downgrowth of hypothalamic neural tissue

•      Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)

•      Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH)

•      These hormones are transported to the posterior pituitary

Pituitary-Hypothalamic Relationships: Anterior Lobe

•      The anterior lobe of the pituitary is an outpocketing of the oral mucosa

•      There is no direct neural contact with the hypothalamus

•      There is a vascular connection, the hypophyseal portal system, consisting of:

•    The primary capillary plexus

•    The hypophyseal portal veins

Adenohypophyseal Hormones

•      The six hormones of the adenohypophysis:

•    Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL

•    Regulate the activity of other endocrine glands

•      In addition, pro-opiomelanocortin (POMC):

•    Has been isolated from the pituitary

•    Is enzymatically split into ACTH, opiates, and MSH

Activity of the Adenohypophysis

•      The hypothalamus sends chemical stimulus to the anterior pituitary

•    Releasing hormones stimulate the synthesis and release of hormones

•    Inhibiting hormones shut off the synthesis and release of hormones

•      The tropic hormones that are released are:

•    Thyroid-stimulating hormone (TSH)

•    Adrenocorticotropic hormone (ACTH)

•    Follicle-stimulating hormone (FSH)

•    Luteinizing hormone (LH)

Growth Hormone (GH)

•      Produced by somatotropic cells of the anterior lobe that:

•    Stimulate most cells, but target bone and skeletal muscle

•    Promote protein synthesis and encourage the use of fats for fuel

•      Most effects are mediated indirectly by somatomedins

•      Antagonistic 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

•      GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors

•      Direct action promotes lipolysis and inhibits glucose uptake

Thyroid Stimulating Hormone (Thyrotropin)

•      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 (Corticotropin)

•      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

•      Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

•    Regulate the function of the ovaries and testes

•    FSH stimulates gamete (eggs or sperm) production

•    Absent from the blood in prepubertal boys and girls

•    Triggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after puberty

Functions of Gonadotropins

•      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

•      In males

•    LH stimulates interstitial cells of the testes to produce testosterone

•    LH is also referred to as interstitial cell-stimulating hormone (ICSH)

Prolactin (PRL)

•      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

The Posterior Pituitary and Hypothalamic Hormones

•      Posterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hormone (ADH) and oxytocin

•      ADH and oxytocin are synthesized in the hypothalamus

•      ADH influences water balance

•      Oxytocin stimulates smooth muscle contraction in breasts and uterus

•      Both use PIP second-messenger mechanisms

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 nonlactating 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

•      The largest endocrine gland, located in the anterior neck, consists of two lateral lobes connected by a median tissue mass called the isthmus

•      Composed of follicles that produce the glycoprotein thyroglobulin

Thyroid Gland

•      Colloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormone

•      Other endocrine cells, the parafollicular cells, produce the hormone calcitonin

Thyroid Hormone (TH)

•      Thyroid hormone – the body’s major metabolic hormone

•      Consists of two closely-related iodine-containing compounds

•    T4 – thyroxine; has two tyrosine molecules plus four bound iodine atoms

•    T3 – triiodothyronine; has two tyrosines with three bound iodine atoms

Effects of Thyroid Hormone

•      TH is concerned with:

•    Glucose oxidation

•    Increasing metabolic rate

•    Heat production

•      TH plays a role in:

•    Maintaining

M.khadar Ali MD