ENDOCRINOLOGY

Endocrine System – response slowly to stimuli but longer lasting (broad)

Nervous system – response rapidly to a certain stimuli (acts on specific muscles or glands)

Exocrine versus Endocrine Glands

 Exocrine gland - secretes products in the body cavities

 Sweat glands, oil gland (sebaceous), mucous, digestive glands

 Endocrine gland - secretes hormones in the interstitial area to the blood

 Ductless glands
 Paracrine
 Autocrine
 Endocrine secretions regulated through either positive or negative feedback mechanisms

Endocrine System
 Network of ductless gland that secretes hormones directly into the blood
 Regulated by means of control of hormone synthesis rather than by degradation
 Ductless glands that intersperse with capillaries serves as route for distribution that travel to circulation
to specific body cells containing specific receptors knowns a Target cells
 Includes:
 Pituitary, thyroid, parathyroid, adrenal, pineal glands
 Organs and tissues that contains cells that secretes hormones:
 Hypothalamus, thymus, pancreas, reproductive organs

Hormones
 Mediator molecule that is released in one part of the body but regulates the activity of cell in other parts
of the body
 Only affects specific target cells
 Neurotransmitters – influence their cells by chemically binding to specific protein receptors
 Down regulation – if the hormones are present in excess, the number of the target cell receptors may
decrease (less sensitive to particular hormone)
 Up regulation – (reciprocal) more sensitive
 Chemical signals produced by specialized cells secreted into the blood stream and carried to a target
tissue
MECHANISMS:

 Positive Feedback - an increased in the product also increases the activity of the system and the
production rate
- Directly related
 Negative feedback - an increased in the product decreases the activity of the system and the
production rate
- majority
Methods of Hormone Delivery
1. Endocrine
 secreted in one location and release into blood circulation
 Binds to specific receptor to elicit physiologic response
2. Paracrine
 Secreted by endocrine cells and released into interstitial space
 Binds to specific receptor of an adjacent cell to affect its function
 Acts on neighboring cells
3. Autocrine
 Secreted in endocrine cells and sometimes released into interstitial space
 Binds to specific receptors on cell of origin resulting to self-regulation of its function
 Acts on the same cell that secreted them
4. Juxtacrine
 Secreted in endocrine cells and remains in relation to plasma membrane
 Acts on immediately adjacent cell by direct cell to cell contact

Control of Hormone Secretion

The majority of endocrine functions are regulated through the pituitary gland, which in turn is
controlled by secretions from the hypothalamus

Classification of Hormones according to Composition or Structure

A. Peptides and Protein
 Glycoprotein
 Polypeptides
B. Steroids
C. Amines

A. Peptides and Proteins

 Synthesized and stored within the cell in the form of secretory granules and are cleaved as needed
 They cannot cross the cell membrane due to their large molecular size and thus produce their effects
on the outer surface of the cells
 They are water soluble
 Not bound to carrier protein
 Water soluble hormones binds to receptor at the outer surface of the plasma membrane, it acts as first
messenger which causes the production of the 2nd messenger inside the cell where specific hormones
stimulate the reactions or response are taking place
 2nd messenger: Cyclic adenosine monophosphate (CAMP)
 Phosphodiesterase – inactivates the CAMP (acts as negative regulators)

Mechanism of Action

 hormones interact with a cell membrane receptor (extracellular receptors) This activates a second
messenger system to affect the cellular function
Hormone synthesis regulation
  Change in the analyte
 Negative Feedback

1. Glycoproteins
 FSH
 HCG
 TSH
 Erythropoietin

2. Polypeptides
 ACTH  Glucagon
 ADH  Insulin
 GH  MSH
 Angiotensin  Oxytocin
 Calcitonin  PTH
 Cholecystokinin  Prolactin
 Gastrin  Somatostatin

B. Steroids
 Lipid molecules that have cholesterol as their common precursor
 Produced by the adrenal glands, ovaries, testes and placenta
 Water insoluble (hydrophobic)
 Examples:
- Aldosterone cortisol estradiol, progesterone, testosterone and vitamin D
Mechanism of Action

 Free hormone is transported across cell membrane to interact with intracellular receptor complex binds
to chromatin producing mRNA; mRNA initiates production of proteins that carry out the function
attributed to the specific hormone
Hormone synthesis regulation

 Negative Feedback

C. Amines
 Derived from an amino acids and they are intermediary between steroid and protein
 Examples
 Epinephrine, Norepinephrine, Triiodothyronine (T3) and thyroxine (T4)

Mechanism of Action

 Epinephrine and norepinephrine do not bind to carrier proteins and interact with the receptor site on the
cell membrane (extracellular)
 Thyroxine and triiodothyronine circulate bound to carrier proteins, with the free hormone being
transported across the cell membrane to interact with the intracellular receptor
 Hormone synthesis regulation

 Nerve stimulation,
 Another hormone (e g thyroxine /TSH)
 Negative feedback

Pineal Gland – Epiphysis cerebri

 Attach to the midbrain
 once dubbed the “third eye”
 Produces MELATONIN - Pinealocyte
 decreases the pigmentation of the skin
 a "natural” sleep aid
 Also regulates circardian rhythm
 Secretions are controlled by the nerve stimuli

Hypothalamus
 Portion of the brain located in the walls and floor of the third ventricle
 Link between the nervous system and the endocrine system
 Supraoptic and paraventricular nuclei produce vasopressin and oxytocin
 Above the pituitary gland and is connected to the posterior pituitary by the infundibulum (pituitary
stalk)
- Thirst, hunger, satiety, temperature, sexual behavior

Hypothalamic Hormones

 Hypophysiotrophic hormones synthesized by parvocellular neurons

 Corticotropin releasing hormone (CRH)
 Gonadotropin releasing hormone ( GnRH)
 Growth hormone releasing hormone (GHRH)
 Thyrotropin releasing hormone (TRH):
 Dopamine (Prolactin inhibitor)
 Somatostatin (GH & Gonadotropin inhibitors)
 Hormones stored in Neurohypophysis are synthesized by magnocellular neurons
 ADH
 Oxytocin

Pituitary Gland (Hypophysis)

 Master gland: Hypothalamus
 Derived from Latin and Greek word “spit mucus”
 was recognized as the “master gland”
 Also known as “Hypophysis”(Greek word – undergrowth under the hypothalamus)
 Also recognized as a Transponder translates neural input into a hormonal or an endocrinologic product
  Located in the small cavity in the sphenoid bone of the skull called the Sella Turcica or Turkish
Saddle
 All pituitary hormones have circadian rhythms
 Divided into three groups
 Anterior adenohypophysis – Pars distalis (larger), Pars tuberalis (forms sheath)
 originates from Rathke’s pouch,
 Intermediate lobe (pars intermedialis poorly developed in humans
 Posterior neurohypophysis – Pars nervosa, Infundibulum
 arises from the diencephalon

5 Types of Cells by Immunochemical Test:

 Somatotrophs
 secrete growth hormone
 Lactotrophs or Mammotropes
 secrete Prolactin – (initiate milk production in mammary glands)
 Thyrotrophs
 secretes TSH/ Thytropin – (controls secretion and other activities of thyroid gland)
 Gonadotrophs
 secrete LH and FSH – (both acts as gonads – estrogen, progesterone, maturation of oocytes in
ovaries, sperm production)
 Corticotrophs
 secrete ACTH/Corticotropin & Melanocyte stimulating hormone
 stimulates cortex of adrenal gland to secrete glucocorticoids (cortisol)

Pituitary Hormones
Tropic Hormones

 TSH
 LH
 FSH
 ACTH
 actions are specific for another endocrine gland

Direct Effectors

 GH
 Prolactin
 act directly on peripheral tissue

A. Anterior Pituitary (Adenohypophysis)

 The “true endocrine gland”
 Regulates the release and production of hormones such as prolactin growth hormone, gonadotropins
TSH, ACTH
 Hormones secreted are either peptides or glycoproteins
  Growth Hormone
 Gonadotropins
 TSH
 ACTH
 Prolactin

Growth Hormone (Somatotropin)

 The somatotrophs comprise over 1/3 of normal pituitary weight

 Stimulated by GHRH
 secretion is inhibited by somatostatin
 median interpulse interval is 2 to 3 hours
 peak occurring at the onset of sleep
 structurally related to prolactin and human placental lactogen

 is considered an amphibolic hormone

directly influences both anabolic and catabolic processes
 directly antagonizes the effect of insulin on glucose metabolism,
 promotes hepatic gluconeogenesis
 stimulates lipolysis

 GH deficiency in children may be accompanied by hypoglycemia in adults hypoglycemia may occur if

both GH and ACTH are deficient

Modifiers which stimulate GH secretion

 Sleep
 Exercise
 Physiologic Stress
 Amino acid (e.g. arginine)
 Hypoglycemia
 Sex steroids (e.g., estradiol)
 α-Agonists (e.g., norepinephrine)
 β-Blockers (e.g., propranolol)

Modifiers which inhibit GH secretion

 Glucose Loading
 β Agonists (e.g., epinephrine)
 α Blockers (e.g., phentolamine
 Emotional/psychogenic stress
 Nutritional deficiencies
 Insulin deficiency
 Thyroxine deficiency
  GH has direct and indirect effects on many tissues
 Indirect effects are mediated by factors that were initially called somatomedins (insulin like growth
factors) because of its structural homology to proinsulin

Gonadotropin (LH & FSH)

 Important markers in diagnosing fertility and menstrual cycle disorders

 Present in the blood of both male and female at all ages
 FSH - aids in spermatogenesis (male) and early folliculogenesis (female)
 LH - Testosterone production (male) and ovulation and final follicular growth (female)

Gonadotropins

 LH acts on thecal cells to cause the synthesis of androgens, estrogens (estradiol and estrone) and
progesterone
 Elevation of FSH is a clue in the diagnosis of premature menopause
 Increased of FSH and LH after menopause is due to lack of estrogen

Thyroid Stimulating Hormone

 Αlpha subunit has the same amino acid sequences of LH, FSH and HCG
 ß subunit carries the specific information to the binding receptors for expression of hormonal activities
 Main stimulus for the uptake of iodide by the thyroid gland
 It acts to increase the number and size of follicular cells of follicular cells it stimulates thyroid hormone
synthesis

Adrenocorticotrophic Hormone (ACTH)

 For the secretion of cortisol

 Produce in response to low serum cortisol regulator of adrenal androgen synthesis
 Deficiency of ACTH will lead to atrophy of the adrenal cortex layers
 Highest level is between 6 to 8 am
 Lowest level is between 6 to 11 pm
 Specimen for testing should not be allowed to have contact with glassnbecause ACTH adheres to glass
surface
 Specimen requirement blood should be collected into prechilled polystyrene (plastic) tubes
 Increased levels: Addison’s disease, ectopic tumors after protein rich meals

Prolactin

 A pituitary lactogenic hormone a stress hormone also important for parturition (childbirth)
 Function in the initiation, maintenance and production of milk
 Lactation entails milk production and secretion/ejection facilitated by Prolactin and oxytocin actions
 Also acts in conjunction with estrogen and progesterone to promote breast tissue development
 Main inhibitory factor dopamine
  Estrogens also directly stimulate lactotropes to synthesize prolactin
 Hyperprolactinemia may also be seen in renal failure and polycystic ovary syndrome
 Physiologic stressors, such as exercise and seizure s, also elevate prolactin
 Stimulation of breasts, as in nursing causes the release of prolactin secreting hormones from the
hypothalamus through a spinal reflex act

Hyperprolactinemia
Examples of medications that cause hyperprolactinemia include:

 Phenothiazines
 Butyrophenones
 Metoclopramide
 Reserpine
 tricyclic antidepressants,
 methyldopa, and antipsychotics that antagonize the dopamine D2 receptor

 Disruption of the pituitary stalk (e g tumors, trauma, or inflammation)

 causes an elevation in prolactin as a result of interruption of the flow of dopamine from the
hypothalamus to the lactotropes the pituitary prolactin secreting cells

Clinical Presentation of patient with Hyperprolactinemia

 Menstrual irregularity/amenorrhea, infertility, or galactorrhea

 Pituitary mass, such as headaches or visual complaints
 Reduced libido or complaints of erectile dysfunction or impotence (men)

Prolactin

 Consequence of prolactin excess is hypogonadism either by

 suppression of gonadotropin secretion from the pituitary
 inhibition of gonadotropin action at the gonad

 Increased levels menstrual irregularity, infertility, renal failure, polycystic ovary syndrome,
hypothyroidism, amenorrhea and galactorrhea
 It is essential to obtain TSH and free T4 (total thyroxine and t3 resin uptake) to eliminate primary
hypothyroidism as a cause for the elevated prolactin

 Specimen requirement blood should be collected 3-4 hours after individual has awakened fasting
sample
 Highest level in the morning is between 4 am and 8 am in the evening, between 8 pm and 10 pm
 B. Posterior Pituitary (Neurohypophysis)
Hormones regulated

 Vasopressin (ADH)
 Oxytocin

 The hormones released by neurohypophysis are synthesized in the supraoptic nuclei (ADH) and
paraventricular nuclei (oxytocin) of the hypothalamus
 Release of the hormones occurs in response to serum osmolality or by suckling
 Hormones produced are controlled by CNS

Oxytocin

 Stimulates contraction of the gravid uterus at term --(Fergusson reflex)

 Released in response to neural stimulation of receptors in the birth canal, uterus and of touch receptors
in the breast
 Stimulates muscle contraction (during delivery and lactation)
 Synthetic preparation of oxytocin are used to increase weak uterine contractions during labor and to aid
in lactation (Pitocin)

Anti- Diuretic Hormone (ADH) / Arginine Vasopressin (AVP)

 Nonapeptide that acts on the DCT and CD of the kidney (V 2 receptors)

 It increases blood pressure - a decreased in blood volume or blood pressure will likewise stimulate
ADH release
 It’s a potent pressor agent and affects blood clotting by promoting factor VII release (V 1 a and V 1 b
receptors in vascular endothelium for vaso constricting properties of ADH)

 Physical and Emotional Stress (surgery) increase ADH output

 Inhibitors of ADH release: ethanol, cortisol lithium
 Potent Physiologic Stimuli to ADH release: emetic stimuli
 Diagnostic test Overnight Water Deprivation (a concentration test) after 8-12 hours without fluid intake,
urine osmolality does not rise above 300 mOsm /kg

In Relation to Osmolality

 Principal regulator of ADH secretion increased concentration in plasma osmolality

 ADH secretion is maximally stimulate d at a serum osmolality of >295 mOsm /kg and suppressed when
the osmolality falls below 284 mOsm /kg
Clinical Disorders (ADH)

 Diabetes Insipidus
 Deficient ADH
 Results in severe polyuria ( ≥ 3 L of urine / day)
 Clinical Pictures include:
 Normoglycemia
 Polyuria with low specific specific gravity
 Polydypsia
 Polyphagia (occasional)

2 Types of Diabetes Insipidus

 True Diabetes Indipidus
 Nephrogenic Diabetes Insipidus

True Diabetes Insipidus

 Hypothalamic/ Neurogenic / Cranial/ Central Diabetes Insipidus

 Deficiency of ADH with normal ADH receptor
 Failure of the pituitary gland to secrete ADH
 There is large volume of urine secreted (3-20 L/day)

Nephrogenic Diabetes Insipidus

 Normal ADH with abnormal ADH receptor

 renal resistance to ADH action
 Failure of the kidneys to respond to normal or elevated ADH level.

SIADH

 Syndrome of Inappropriate Antidiuretic Hormone Secretion

 Refers to the sustained production of ADH in the absence of a known stimuli
 Characterized by
 decreased urine volume
 low plasma osmolality
 hyponatremia
 Normal or elevated urine Na levels
 Low serum electrolytes