Thread: Endocrine system

Neuroendocrine System

Nervous system controls through nerve impulses conducted by axons. Responses occur within milliseconds. Relatively local, specific effects. Stops when stimulus stops, adapts quickly.
Endocrine system controls through hormones transported in the blood stream. May have widespread general effects. Responses occur after seconds to days and are more prolonged. Adapt slowly
Endocrine Glands
§ No ducts – secretion into fluid around cells diffuses into capillaries
§ Pituitary, thyroid, parathyroid, adrenal and pineal are examples.
§ Many organs have partial endocrine function – hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, small intestine, skin, heart.

Hormones– long distance chemical messengers that travel in blood or lymph throughout body.

Hypothalamus and Pituitary Glands
Anatomy
Hypothalamus floor and walls of third ventricle. Interfaces with ANS
Pituitary -
Anterior [adenohypophysis]
75% of gland – ectodermal origin
regulated by “releasing” hormones from hypothalamus – no neural connection – joined through hypophyseal portal system.
5 kinds of gland cells produce trophic hormones (affect other endocrine tissues).
Somatotrophs (hGH)
Thyrotrophs (TSH)
Gonadotrophs (FSH, LH)
Lactotrophs (Prolactin)
Corticotrophs (ACTH, MSH)
Posterior [neurohypophysis] – mass of neuroglia and nerve fibers.
25%, ectodermal origin; stores and releases hormones – doesn’t
make them
Ex. Oxytocin and ADH from hypothalamus
Hypothalamus Hormones
In diencephalon – integrates nervous system & hormones & controls ANS.
Synthesizes at least 9 hormones- 7 regulate the pituitary.
Regulates growth and development, metabolism, homeostasis.
Controls secretion of other hormones by other glands.
Intimately in contact with pituitary by hypophyseal portal system [primary
capillary plexus of infundibulum connected by hypophyseal portal veins with secondary capillary plexus in anterior pituitary.]

Hormones produced by the hypothalamus
A. Growth Hormone Releasing Hormone (GHRH)
Target = anterior pituitary
Effect = stimulates release of growth hormone (GH)
Regulation = Plasma levels of glucose, fatty acids, and amino
acids; sleep, ANS and other hormones.

B. Growth Hormone Inhibiting Hormone (GHIH)
Target = anterior pituitary
Effect = inhibit release of GH
Regulation = Plasma levels of glucose, fatty acids and aa's

C. Thyrotropin Releasing Hormone (TRH)
Target = anterior pituitary gland
Effect = stimulate release of Thyroid-stimulating hormone (TSH)
Regulation = plasma levels of TSH and glucose; metabolic rate

D. Corticotropin Releasing Hormone (CRH)
Target = anterior pituitary gland
Effect = stim. release of adrenocorticotropic hormone (ACTH)
Regulation = blood glucose levels, stress, interleukin -1

E. Gonadotropin Releasing Hormone (GnRH)
Target = anterior pituitary gland
Effect = stimulate release of Follicle Stimulating hormone (FSH)
and Luteinizing hormone (LH)
Regulation = Females - plasma estrogen and progesterone
Levels; Males - plasma testosterone levels

F. Prolactin Releasing Hormone (PRH)
Target = anterior pituitary gland
Effect = stim. release of prolactin (PRL)
Regulation = suckling

G. Prolactin inhibiting Hormone (PIH)
Target = anterior pituitary
Effect = inhibit PRL release
Regulation = suckling, plasma estrogen & progesterone levels

** 2 hormones are produced in the hypothalamus, and stored in special neurosecretory cells in the posterior pituitary gland.
H. Oxytocin (OT) – from paraventricular nucleus
Target = smooth muscle in uterus and breast
Effect = contraction of muscle (labor, milk ejection, sexual
arousal – “cuddle” hormone.)
Regulation = hormonal changes during pregnancy, suckling
I. Antidiuretic Hormone (ADH) – from supraoptic nucleus [=
vasopressin]
Target = kidney
Effect = decrease sweat and urine output; constrict arterioles &
increase blood pressure
Regulation = blood osmotic pressure, stress, drugs
[alcohol inhibits ADH].
Pituitary Hormones – 5 are trophic [stimulate other endocrine structures to release hormones]
A. Human Growth Hormone (hGH) or Somatotropin
Target = general [mainly bones & skeletal muscles.]
Effect = stimulates synthesis and production of insulin-like
growth factors (cause release of glucose, like insulin does.) stimulate cell growth and division; increases rate of protein synthesis and rate of fat catabolism, decreases rate of glucose catabolism (increase metab.)
Regulation = GHRH, GHIH
Also affected by stress, nutrition and sleep patterns.


B. Thyroid-stimulating Hormone (TSH)
Target = thyroid gland
Effect = stim. secretion/release of T3 and T4
Regulation = TRH

C. Adrenocorticotropic Hormone (ACTH)
Target = cortex of the adrenal gland
Effect = stimulate prod. /release of glucocorticoids
Regulation = CRH. Also affected by stress, hypoglycemia.

D. Follicle-Stimulating Hormone (FSH)
Target = gonads (ovary, testis)
Effect = stimulate production of gametes (male and
female) stimulates production of estrogen (female)
Regulation = GnRH, inhibin, estrogen (F) & testosterone (M)

E. Luteinizing Hormone (LH)
Target = gonads
Effect = (F) stimulates ovulation, formation of corpus luteum and prod. of Estrogen and Progesterone. (M) stimulates prod. of testosterone, LH also called interstitial cell stimulating hormone (ICSH) in male
Regulation = GnRH

F. Prolactin (PRL) or Lactogenic Hormone
Target = breast
Effect = milk production
Regulation = PRH, PIH, estrogen.

G. Melanocyte-Stimulating Hormone (MSH)
Target = melanocytes
Effect = increases production of melanin; CNS neurotransmitter
Regulation = MRH, MIH
Produced from pro-opiomelantocortin POMC, that also can yield 2 natural opiates, an enkephalin & endorphin.

Control of Pituitary Secretion – timing and amount of secretion are regulated by hypothalamus, brain centers & feedback from target organs.
Hypothalamus & Cerebral Control – releasing & inhibiting hormones. Brain monitors conditions and stimulates their release.
Neuroendocrine reflexes affect posterior lobe of the pituitary - in response to neurosensation [e.g., suckling].
Feedback from targets – negative feedback inhibition for the most part [note oxytocin response is positive feedback].
Other Endocrine Glands
Pineal Gland – roof of third ventricle of brain – capsule of pia mater. Decreases in size with age.
Cells = pinealocytes
Function – not clear
Produces melatonin [at night], and serotonin [by day] – may affect circadian rhythms, timing of puberty, and mood [SAD & PMS]

Thymus – over heart – functions in immunity, decreases in size with age.
Produces thymopoietin and thymosin needed for T cell maturation.

Thyroid Gland – Inferior to larynx; largest endocrine gland.
General
Lateral lobes connected by isthmus anterior to trachea
Follicles – made of follicular cells produce T3 and T4 upon TSH
stimulation
Parafollicular cells – produce calcitonin
Hormones are stored in large quantities – only gland that does this
In colloid in follicle cavity
Thyroid Hormones
T3, T4 [main]
Target – general
Effect – regulate O2 use, basal metabolic rate, growth and
development - T3 more potent than T4
Regulation – TSH from pituitary, TRH from hypothalamus
Calcitonin
Target – bone
Effect – inhibit osteoclasts, decrease Ca2+ release into blood,
increase Ca2+ uptake into bone
Regulation – Ca2+ levels
Parathyroid Glands – posterior surface of lateral lobes of thyroid – 2 per side
PTH – parathyroid hormone – in response to hypocalcemia.
Increases number and activity of osteoclasts. Most important
hormone in regulation of Ca2+ balance.
Increases bone resorption, which increases blood Ca2+ & HPO42-
Kidney changes:
Increase rate of removal of Ca2+ and Mg2+ from urine and
return to blood
Net effect – increases circulating Ca2+ and decrease HPO42-
Calcitonin is PTH antagonist
Also promotes formation of calcitriol from vitamin D, which
increases rate of Ca2+, Mg2+, and HPO42- from GI
Control – Negative feedback via blood Ca2+ levels
Adrenal Glands – 2, 1 on top of each kidney – 2 regions – cortex and medulla
Adrenal Medulla
Inner part of adrenal – not essential to life.
Chromafin cells – modified postganglionic sympathetic neurons
specialized for hormone secretion.
Produce catecholamines – epinephrine [80%] and norepinephrine – fight or flight response of sympathetic system [glycogenolysis, gluconeogenesis, glucose-sparing, etc.]
Link to cortex – under stress, catecholamine secretion stimulates corticosterone secretion.
Cortex – 80-90%
Derived from mesoderm
Produce over 2 dozen steroid hormones essential to life from cholesterol.
3 zones:
Zona glomerulosa – outer zone
Produces mineralcorticoids – affect homeostasis of Na+ and
K+ - 3 versions
Aldosterone – 95%
· Acts on kidney tubules
· Causes resorption of Na+ which also increases
resorption of Cl-, HCO3- and H2O
· Promotes secretion of K+, which increase K+ excretion
· Control – 4 mechanisms
1. Renin-angiotensin pathway
Decrease in blood volume causes decrease in blood pressure This stimulates renin secretion by the kidney, which causes Angiotensinogen to be converted to angiotensin I in the liver
This promotes conversion to angiotensin II in the lung, which causes Aldosterone secretion which increases blood volume and increase in blood pressure.
A second target for angiotensin II is arteriole walls – they constrict which further increases blood pressure.
2. Plasma Na+ and K+ concentrations – increase inhibits, decrease stimulates.
3. ACTH – in stress, causes increases in aldosterone.
4. ANP – inhibits rennin-angiotensin system.
Zona fasciculata – secretes glucocorticoids – affect glucose
Homeostasis. These regulate metabolism and resist stress
Cortisol, corticosterone, cortisone, Cortisol is 95% of what is made
Effects – stimulate:
· Protein breakdown/construction
· Gluconeogensis (formation of glucose)
· Lipolysis – breakdown of lipids
· Stress resistance – increases glucose and blood pressure
· Anti-inflammatory – reduce number of mast cells which reduces release of histamine; also decrease vessel permeability which reduces swelling, but also slows healing
· Depression of immunity – helps with organ transplants

Control – negative feedback – blood levels of glucocorticoids decrease which causes increase in CRH, which stimulates release of ACTH from the pituitary, which goes to cortex and increases glucocorticoid secretion.
Zona reticularis – produces androgens & some estrogens
This is not significant in males since the testes make more
In females – affect libido, increase axial and pubic hair,
Affect pre-pubertal growth spurt
Pancreas – endocrine and exocrine – posterior and slightly inferior to stomach
Exocrine function – 98% of total – production of digestive enzymes by
acinar cells
Endocrine function – Islets of Langerhans; 3 main types of cells
α–- produce glucagon
β – produce insulin
Δ – produce somatostatin
Hormones
Insulin
Target – general
Effect – lowers blood glucose & accelerates diffusion of glucose into cells [except kidney, liver & brain], Increases glycogenesis, increases uptake of amino acids and peptide formation (decreases gluconeogenesis), promotes glucose conversion to fat & promotes cellular respiration. Decreases glycogenolysis.
Regulation –blood levels of glucose, amino acids & fatty a’s.
Glucagon
Target – liver
Effect – increases blood glucose levels by stimulating gluconeogenesis and glycogenolysis.
Regulation – blood glucose levels, ANS and Insulin (elevated glucose in blood causes secretion of insulin)
Somatostatin
Target – digestive tract and pancreas
Released in response to elevated glucose, fatty acids & aa’s.
Inhibits secretion of glucagon and insulin
The Gonads
Ovaries
Estrogens [granulose cells of follicle & corpus luteum] and progesterone
Regulate female reproductive cycle
Maintain pregnancy
Prepare mammarys for lactation
Develop and maintain secondary sexual characteristics
Inhibin – suppresses FSH
Testes
Testosterone – androgen [by interstitial cells]
Regulates production of sperm, sex drive
Regulates development of male secondary characteristics
Inhibin [by sertoli cells]
Other Hormone Producing Structures
Heart – ANP
Reduces blood volume, pressure and sodium concentration.
Inhibits aldosterone
Skin – Cholecalciferol
Inactive vitamin D formed by UV radiation à liver à kidney for full activation [calcitriol].
Essential for calcium absorption from intestines.
Liver – associated with production [often elsewhere] of 5 hormones – erythropoietin, angiotensin II, calcitriol, insulin-like growth factors I, Hepcidin [promotes uptake of iron]
Kidney – Erythropoietin [Stimulates rbc production]. Calcitriol. Renin – renin- angiotensin system.
GI – Enteroendocrine cells
Regulate digestive functions.
Paracrines – local hormones.
Placenta - Produces estrogen, progesterone, hCG.
Adipose – Leptin – secreted after glucose uptake – suppresses appetite.
Resistin – an insulin antagonist.

Hormones & Their Actions
Chemistry
Steroids
Made from cholesterol nucleus with variable attachments. Glands derived from mesoderm – gonads and adrenal - EX. Aldosterone, cortisol, vitamin D, androgens
Peptides and Proteins ( 3 – 200 amino acids)
Synthesized in the rough endoplasmic reticulum. Some have carbohydrate groups = glycoproteins - EX. – TSH, oxytocin, ADH, etc.
Monamines - Amino acid – based
Catecholamines – epinephrine, norepinephrine, dopamine from Tyrosine. Histamine from histidine. Serontonin, and melatonin from tryptophan.
Thyroxine [thyroid hormones] - 2 iodinated tyrosine molecules coupled together. T3, T4
Hormone synthesis
Steroids – from cholesterol – vary in functional group attachments.
Peptides – transcription, translation, etc. à inactive preprohormone à RER à prohormone à Golgi à secretion
Monamines – thyroxine example
Synthesis - Made from thyroglobulin – glycoprotein containing tyrosine – produced by follicular cells.
Add 3 or 4 I’s
Iodination process – 2I- à I2
I2 + Tyr à either 1 iodo or 2 iodo Tyr
T1 +T2 à T3
T2 + T2 à T4
Released from thyroglobulin by lysosomes
Transport - both are carried in blood by thyroxin-binding
globulin made in liver
Hormone Transport
Monamines & peptides are mostly hydrophilic, can be easily transported in blood.
Steroids & thyroid hormone are hydrophobic, so require assistance. They are moved attached to “transport” proteins – made by the liver.
Transport proteins also protect from degradation, and elimination.


Hormone receptors & mode of action

Hormone Target Cell Specificity
Receptors – proteins or glycoproteins.
§ On target cells – other cells not affected.
§ Constantly replenished
§ Response to hormone concentration –
Saturation – all are occupied. ↑ hormone will have no effect.
§ Control – “if a hormone is prevented from interacting with its receptors, it
cannot perform its normal functions.”
§ Variable response – different cells may have receptors for the same
hormone, but produce different responses to it.
EX. Insulin – In fat cells, it stimulates uptake of glucose & fat synthesis,
in the liver it stimulates amino acid transport and glycogen synthesis, in
the pancreas it inhibits glucagon-related reactions.
Steroids and thyroid hormone
Receptors are inside the target cell
Action: Diffuse from blood through plasma membrane into cell.
Bind to and activate receptors in nucleus.
Activated receptor binds to DNA.
DNA is transcribed, & new mRNA is produced that directs synthesis of proteins, usually enzymes.
Thyroid hormone – in cell all is converted to T3.
T3 binds to mitochondria to ↑ cellular respiration; binds to ribosomes & ↑ rate of protein synthesis; binds to DNA receptors ↑ transcription.
Peptides & catecholamines - Second Messenger Systems

Action [Ex. Glucagon]
Hormone diffuses from blood to target cell & binds to membrane receptor.
This activates “G” proteins attached to the inside of the membrane,
which in turn activates adenylate cyclase (AC) also on the inside AC converts ATP to cAMP in cytosol.
cAMP activates protein kinases (they add phosphates to proteins).
This may either activate or inactivate the proteins.
Control – phosphodiesterase inactivates cAMP
Increasing or decreasing cAMP.
Increases occur with ADH, TSH, ACTH, glucagon, epinephrine,
hypothalamic releasing hormone.
Decreases occur with GHIH, ANP.

Enzyme amplification – one hormone molecule may activate many G’s, each of
which may then activate many AC’s, each of which may produce many cAMPs, etc.
Modulation of sensitivity
Down-regulation – number of receptors decreases when concentrations of
hormone are high – tissues become less sensitive.
Up-regulation – number of receptors increases when concentration of
hormone decreases – tissue becomes more sensitive.
Hormone interactions: synergistic [works with another hormone for an effect], permissive [enhances response to another hormone secreted later], antagonistic [works against another hormone]
Half-Life, Onset, and Duration of Activity

Half-life – measures persistence of a hormone in circulation – usually a fraction of a minute to 30 minutes.

Stress and General Adaptation Syndrome (GAS) – DOESN’T maintain normal environment
Response to prolonged, extreme or unusual stress
Stressor – and disturbance – temperature, toxins, poisons, heavy
bleeding, emotional upheaval
GAS – 3 stages
1 – Alarm Reaction = Fight or flight [short-term response]
hypothalamus stimulates ANS and adrenal medulla à
epinephrine/ norepinephrine; short lived
Consumes glycogen stores
2 – Resistance Stage [long-term] – provide alternative fuels when glycogen has been depleted – dominated by cortisol.
Mediated by hypothalamus releasing hormones:
CRH – stimulates ACTH production, which stimulates glucocorticoid [cortisol] secretion by adrenal.
è Fat breakdown, inhibits protein synthesis, immune response, etc.
If stress removed – body returns to normal.
3 – Exhaustion – if stress continues past ability of Resistance Reaction to function à rapid decline & death [heart or kidney failure or
overwhelming infection].

Stress and Disease – stress can temporarily inhibit components of the
immune system and produce gastritis, ulcerative colitis, irritable bowel syndrome, migraines, anxiety and depression.

Eicosanoids & Paracrines
Eicosanoids – 20 C FA chains – derived from arachidonic acid in phospholipids in cell membranes. – Important considerations in pharmacology.
Leukotrienes – mediate allergic & inflammatory reactions
Prostacyclin – blood vessel walls – inhibits clotting and vasoconstriction
Thromboxanes – platelets – stimulate vasoconstriction & clotting when platelet is activated.
Prostaglandins
Anti-inflammatories
Steroidal – inhibit release of arachodonic acid and thus formation of eicosanoids.
Non-steroidal – stop action of enzyme needed for prostaglandin synthesis
Endocrine Disorders
Homeostatic Imbalances – hypothalamus/pituitary
Hyper secretion of prolactin – may be due to adenohypophyseal tumors- inappropriate lactation, loss of menses, infertility.
Diabetes Insipidus – deficiency of secretion of ADH – Huge losses of urine, no sugar.
GH - Gigantism [hyper] & dwarfism [hypo]

Homeostatic Imbalances – Thyroid
Hypothyroidism – myxedema – may be from thyroid defect or failed TSH or TRH release. Low metabolic rate, chills, thick dry skin, puffy eyes, lethargy. If due to lack of I – can develop goiter. Infantile version = cretinism – can be prevented with thyroid hormone replacement therapy, but can’t be reversed.
Hyperthyroidism – Grave’s disease. May be autoimmune disease. Elevated metabolic rate, weight loss, rapid irregular heart beat, exophthalmos.

Homeostatic Imbalances – Adrenal Cortex
Cushing’s Disease – overproduction of glucocorticoids – buffalo hump on back, edema, hypertension. Due to steroid therapy or pituitary tumor.
Addison’s Disease – hyposecretion. Fluid loss and hypotension.

Homeostatic Imbalances – Pancreas
Diabetes Mellitus –hyposecretion or hypoactivity of insulin. Elevates blood sugar levels, glycosuria, weight loss. Ketoacidosis [from lipemia]. 3 signs – polydipsia [excessive thirst], polyphagia [excessive hunger], polyuria [huge urine output]. Also hyperglycemia, glycosuria, ketonuria.

Type I – insulin-dependent [juvenile]. Involves depletion of beta cells. Requires insulin supplementation.

Type II – non-insulin dependent [insulin levels are normal or elevated]. Problem is insulin resistance. Adult-onset [40+]. Associated with obesity.

Fat catabolism à↑ free FA’s à ↑ ketone bodies à osmotic dieresis, flushing of Na and K, acidosis à diabetic coma.

Long-term degenerative effects on vascular and nervous system – compromised circulation à gangrene. Nerve damage à impotence, loss of sensation, etc.
Hypoglycemia – excess insulin, low blood sugar, anxiety, tremors, weakness.

Originally Posted by Powermaster

Source of this stuff: Anatomy & Physiology II

Are you professor Bowen?

Nope, I took her years back. I spent Sat night retyping my old notes. Had no idea she has them posted online now? Whatever it was a good refresher, I hope someone gets as much out of it is I did.