Lect. 1 - General Principles Flashcards
three large regulatory systems in mammals that are responsible for the transfer of information between different parts of the organism and participate in maintaining homeostasis in the cells, tissues and entire body:
nervous-
immune- &
endocrine systems
Acromegaly is
a condition where the body produces too much growth hormone
Endocrinology is
the study of chemical communication systems that provide the means to control a huge number of physiologic processes.
Endocrine glands arise during
development from all three embryologic tissue layers:
(endoderm, mesoderm, ectoderm).
The type of endocrine product is determined by which tissue layer a gland originated in.
Glands of ectodermal and endodermal origin produce (2)
peptide and amine hormones.
Glands of mesodermal-origin secrete hormones based on
lipids.
Two major categories of glands in the body
Exocrine & endocrine Glands
Exocrine glands have
ducts that carry their secretory product to a surface.
These glands include the sweat, sebaceous, and
mammary glands and, the glands that secrete digestive enzymes.
The endocrine glands do not have
ducts to carry their product to a surface. They
are called ductless glands.
The secretory products of endocrine glands are called hormones and are secreted
directly into the blood.
Name all “classic” endodrine glands. (8)
- Adrenals
- Hypothalamus
- Gonads (ovary, testis)
- Pancreas (islets of Langerhans)
- Parathyroid glands
- Pituitary
- Pineal gland
- Thyroid gland
Pineal gland produces?
melatonin
Posterior pituitary/neurohypophysis produces?
oxytocin and vasopressin/ADH
Anterior pituitary/adenohypophysis produces? (6)
Corticotropin (ACTH)
FSH
Growth hormone/somatotropin
LH
Prolactin
Thyrotropin (TSH)
The thyroid gland produces what hormones?
triiodothyronine (T3)
thyroxine (T4)
Calcitonin
Parathyroid hormone function?
Regulates plasma Ca2+ and phosphate levels.
A hormone the heart produces
atrial natriuretic peptide / hormone
2 hormones the liver produces
angiotensinogen
insulin-like growth factors
3 hormones produced in the adrenal cortex
aldosterone
cortisol
androgens
adrenal medulla produces
epinephrine & norepinephrine
hormones produced by the kidneys
renin
erythropoietin
1, 25 dihydroxy-vitamin D3 (calcitriol)
Calciferol is a broad term for vitamin D compounds, including D2 and D3.
skin produces what hormone
When the skin is exposed to (UVB) radiation from the sun, a compound called 7-dehydrocholesterol, present in the skin, is converted into previtamin D3.
Previtamin D3 is then converted into vitamin D3 (cholecalciferol) through a heat-dependent process.
Vitamin D3 is subsequently metabolized in the liver and kidneys into its active form, calcitriol.
Calcitriol is the same as 1,25 dihydroxy-vitamin D3.
Calciferol is an umbrella term for all D vitamin compounds.
aldosterone broad function?
Na+ and K+ homeostasis.
Aldosterone acts on the kidneys, specifically on the cells of the distal tubules and collecting ducts, to enhance the reabsorption of sodium ions.
sodium retention, potassium excretion
Acid-Base Balance
Hormones are complex chemical substances produced by
ductless endocrine glands or individual hormone producing cells (incretory glandular cells) that are secreted directly into the bloodstream and act as humoral regulators of the organism.
Neuroendocrine signaling:
Neurosecretory neurons release neurohormones into the circulatory system
define autocrine regulation
Cells release local regulators that
regulate the same cells that produced it.
define paracrine regulation
Cells release local regulators that
diffuse through extracellular fluid to regulate nearby cells
example: insulin-like growth factor 1 (IGF-1)
The target cell hormone receptors have two main functions:
(1) to recognize and bind with high affinity to their particular hormones
(2) to initiate a signal to appropriate intracellular effectors
up-regulation =
down-regulation =
an increase and decrease in hormone receptors
Sensitivity is related to
the number of receptors which are constantly
being synthesized and degraded.
Physiological conditions affect receptor
number and affinity (pH, temp. ion concent. etc.).
What is the GH IGF-1 axis?
What is the relationship between GH and IGF-1?
The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is the principle endocrine system regulating linear growth in children.
GH induces the generation of insulin-like growth factor 1 (IGF-1, also called somatomedin 1) in the liver and regulates the paracrine production of IGF-1 in many other tissues. The cascade of the growth hormone axis.
Target cell activation depends on 3 factors:
- Levels of the hormone
- Relative number of receptors on the target cell
- Affinity of those receptors for the hormone
Agonists are
molecules that bind to the receptor and induce all the post-receptor events that lead to a biologic effect.
Antagonists are
molecules that bind to the receptor and block binding of the agonist, but fail to trigger intracellular signalling events.
Example of a Progesterone receptor agonist
Megestrol acetate is used in dogs and in cats to control heat cycles (estrus) and in bitches to treat false pregnancy.
Example of a Progesterone receptor antagonist
Aglepristone (Alizin)
Effective on uterine progesterone receptors, with a binding affinity three times stronger than endogenous progesterone, providing effective competitive antagonism thus blocking progesterone which is responsible for implantation and pregnancy maintenance.
Cortisol (adrenal cortex) acts on the
hypothalamus/anterior pituitary gland to inhibit
ACTH / adrenocorticotropic hormone
This is an example of negative autoregulation.
Testosterone (testis) acts on the
hypothalamus/anterior pituitary gland to inhibit
testosterone is part of a negative feedback mechanism that inhibits GnRH release by the hypothalamus and LH release by the pituitary.
Oestradiol (ovary) acts of the
hypothalamus/anterior pituitary gland to stimulate
luteinizing hormone (LH)
This is an example of positive autoregulation.
define Circadian
24 hour cycle
(circa = about; dies = day)
define Ultradian
a cycle shorter than 24 hours
define Infradian
a cycle that is longer than 24 hours
(i.e. 21 day estrous cycle in cows)
hormones can chemically be: (name 5 substances)
amino acids
fatty acids
peptides
proteins
steroids (lipid based)
melatonin is derived from
the essential amino acid, tryptophan
catecholamines (apinephrine and dopamine), and thyroid hormones are derived from?
the non essential amino acid tyrosine
Tyrosine is the parent amino acid for (2)
catecholamines &
thyroid hormones
Catecholamines are made by modifying ?
the side groups of tyrosine
Thyroid hormones are synthesized from
2 tyrosines and iodine atoms
name Lipid-Derived Hormones
steroids such as testosterone and estradiol,
progesterone, cortisol, aldosterone
Most lipid hormones are derived from
cholesterol and thus are structurally similar to it.
Chemically, these hormones are usually
ketones or alcohols; their chemical names will end in “-ol” for alcohols or “-one” for ketones.
e.g. estradiol and testosterone
Typically, endocrinologists classify steroid hormones into five groups of molecules, based primarily on the receptor to which they bind. Name the groups.
Androgens (testosterone)
Estrogens (estradiol)
Glucocorticoids (ie. cortisol)
Mineralocorticoids (aldosterone)
Progestogen/progestins (progesterone)
Following secretion, all steroids
bind to some extent to plasma proteins.
This binding is often low affinity and non-specific (e.g. to albumin), but some steroids are transported by specific binding proteins, which clearly affects their halflife and rate of elimination.
Prostaglandins, prostacyclins, leukotrienes and thromboxanes are derived from
fatty acids
Arachadonic acid is the most abundant precursor for these hormones.
Prostaglandins tyicpically act where in respect to location of release
Prostaglandins are local hormones but
prostaglandin F2α (PGF2α) can also act
as a blood borne hormone.
Many hormones are polypeptides, but most are
proteins.
Explain regulated secretion of peptide hormones.
The cell stores hormone in secretory granules and releases them in “bursts” when stimulated. This is the most commonly used pathway and allows cells to secrete a large amount of hormone over a short period of time.
e.g. GH
Explain Constitutive secretion of peptide hormones.
The cell does not store hormone, but secretes it from secretory vesicles as it is synthesized.
e.g. FSH
2 functions for hormones binding to specific binding proteins
- (i) increase the solubility of hydrophobic hormones
- (ii) protect the hormone from rapid metabolism by proteolytic enzymes in blood
Peptide or protein hormones (pituitary, hypothalamic, and parathyroid hormones; and insulin) are water soluble and circulate mostly how?
in free (unbound) forms.
how do Insulin-like growth factor (IGF) and Growth hormone travel?
IGF has 6 carrier proteins.
Growth hormone has also carrier proteins.
Water-soluble hormones generally have a short half-life because
they are catabolized by circulating enzymes.
For example, insulin has a halflife of 3 to 5 minutes and is catabolized by insulinases.
Lipid-soluble hormones, such as cortisol and adrenal androgens, are transported how?
bound to a carrier or transport protein and
can remain in the blood for hours to days.
what can free hormones do that bound can’t
signal a target cell.
Because an equilibrium exists between the concentrations of free hormones and hormones bound to plasma proteins, a significant change
in the concentration of binding proteins can affect
the concentration of free hormones in the plasma.
The principal steroid binding proteins in
plasma are
albumin,
corticosteroid binding globulin (CBG, transcortin),
sex-hormone binding globulin (SHBG) which
is also known as testosterone-estradiol-binding globulin (TeBG).
The effect of hormone on the tissue is determined by:
- Hormone concentration in blood
- Presence of hormone receptors and post-receptor mechanisms
all hormone receptors can be categorized into one of two types, based on
their location within the cell:
cell surface receptors or
intracellualr receptors
Principle Mechanism of action for cell surface receptors
Generation of second messengers which alter the
activity of other molecules - usually enzymes - within the cell.
Principle Mechanism of action for intraceluular receptors
Alter transcriptional activity of responsive genes.
Group-I hormones are
Fat-soluble hormones (steroid hormones) that are hydrophobic or lipophilic. They are synthesised from cholesterol and thus classified under Group-I hormones.
The Group-I hormones quickly diffuse in the plasma membrane, reach the cytosol where they can bind the intracellular receptor.
The Group-II hormones bind to
the extracellular domain of the cell receptors present on the plasma membrane
an example of a secondary messenger
adenylyl cyclase
What is JAK-STAT
JAK: “just another kinase”
STAT: signal transducers and activators of
transcription.
a family of signal transducer molecules
explain Pseudohypoparathyroidism shortly
impairment in ability to regulate Ca+ & Phos homeostasis.
PTH is produced in normal amounts but is unabe to prodduce effect due to a defect in the signal transduction pathway, adenyl cyclase is not activated.
resistance or unresponsiveness to parathyroid hormone
The time between hormone pulse intervals can range from
minutes to hours
Rceptor recognition and binding is followed by what 3 broad steps:
signal transduction,,
phosphorylation &
intracellular pathway activation
tropic versus trophic
Tropic hormones are released by an endocrine gland and act upon another endocrine gland (e.g. thyrotropin).
Trophic hormones stimulate growth in target tissues (e.g. GH).
Note: All the tropic hormones of the anterior lobe are simultaneously trophic hormones, in whose absence their target glands atrophy.
