Hormonen en Homeostase
HC 1 + 2 – General principles of endocrinology
Physiology: The study of the normal functioning of a living organism and its component parts, including
all its chemical and physical processes
Homeostasis: the state of equilibrium (balance between opposing pressures) in the body with respect
to various functions and tot he chemical compositions of the fluids and tissues. The ability of the body
to maintain a relatively constant internal environment (self regulation)
Disturbances end up in the
buffer zone in the first place.
The high peaks and low lows
are here dampened, so that
we can handle these
disturbances. In order to
have homeostasis we need
processes which dampen the
disturbances from the
environment.
Een organisme moet compenseren voor een verlies in homeostase. Als dit
lukt en compensatie lukt → wellness. Wanneer dit niet lukt → ziekte.
Pathophysiology vs. Physiology.
External:
- Seasons
- Behavior of conspecifics
- Diet/fasting
- Intoxication
- Trauma/infection
Internal:
- Developmental programs
- Failure of cell processes, e.g.
o Abnormal cell growth
o Autoimmmune antibodies
There are a few homeostatic setpoints. These can be fixed like [Ca2+] or [Glucose] in blood and body
temperature in warm-blooded animals. There are also variable setpoints, like ontogenesis and
,temporal cycles (Day/night, Ovarian cycles, seasonal reproduction, Other seasonal events (e.g.
migration, hibernation))
Setpoints is like a balance. When there is an imbalance, something has to happen. A stimulus provokes
a change in variable. This change is being detected by a receptor. This signal is sent along afferent
pathways to a control center. Output is that information is sent along efferent pathway to effector with
the effect to send feedback to influence magnitude of stimulus and returns variable to homeostasis.
The endocrine system and the nervous system jointly maintain homeostasis.
Hormones respond to:
- Changes in internal balance
- Physical and emotional stress
- Environment
o Photoperiod, temperature, food availability, predators, pathogenst etc.
Hormones regulate:
- Internal environment
- Growth and development
- Metabolism
- Reproduction
Traditional definition → Hormone is a compound, produced by a gland not connected to the outside
world, secreted into the blood, with a physiologic or morphogenetic funtion in the body, usuall distant
from the site of production.
But, hormones can also be produced by organs/tissues having a different primary funtion. Also,
compounds, such as Na, glucose, NO and CO2 can act as a signaling molecule, but are not considered
hormones. Besides, we also see hormones being transported through intercellular fluid.
New definition: “Chemical secreted by a cell or group of cells into the blood for transport to a (distant)
target where it acts in very low concentrations (to affect growth, development, homeostasis, or
metabolism)
Endocrinology: study of hormones
,Classical hormones
- Hypothalamus produces releasing/inhibiting hormones
- Pituitary gland: frontal lobe: TSH, GH, ACTH, LH, FSH, PRL. Intermediate lobe: MSH. Neural lobe:
ADH, oxytocin.
- Thyroid gland: thyroid hormone, calcitonin
- Parathyroids: PTH
- Adrenal glands: cortex: aldosterone, cortisol, androgens. Medulla: adrenaline (epinephrin)
- Pancreas: insulin, glucagon
- Ovaries/testes: reproductive hormones.
Non-classical hormones:
- Brain: Neuropeptides (and more)
- Heart: Atrial natriuretic peptide
- Liver: Angiotensinogen Insulin-like growth factor
- Stomach: Gastrin, Ghrelin
- Intestine: CCK, secretin, incretins (e.g. GLP-1, GIP)
- Kidney: Erythropoietin, calciferol (aka 1,25-dihydroxyvitamin D)
- Skin: Vitamin D3
- Adipose: Leptin, adiponectin, …
- Placenta: Estrogen, progesterone, choriongonadotropin and somatomammotropin
- Several tissues: Growth factors, steps of steroid production (e.g. androgen estrogens)
Classification of hormones:
, - Site of production
o Glandular hormones
o Tissue hormones
o Growth factors
o pheromones
- Biochemistry
o Peptides/proteins
o Steroids
o Amino-acids
derivatives
- Receptor type
o Membrane
o Nuclear
Peptide hormone synthesis: mRNA op ribosomen bindt aminozuren aan elkaar tot een peptideketen,
wat ook wel preprohormonen worden genoemd. Vervolgens wordt deze keten het ER lumen in
gestuurd door een signaalsequentie van aminozuren. Enzymen in het ER knippen de signaalsequentie
eraf, waarmee het een prohormoon wordt. Het prohormoon passert van het ER naar het golgi complex.
Secretoire blaasjes met enzymen en prohormonen snoeren af van het Golgi. De enzymen knippen de
prohormen in één of meerdere actieve peptiden plus additionele peptide fragmenten. De secretoire
blaasjes laten hun inhoud vrij via excocytosis in de extracellulaire ruimte. Het hormoon beweegt de
circulatie in voor transport naar zijn target.
Steroid hormone synthesis: meeste steroid hormonen worden in de adrenal cortex of gonaden (ovaries
en testes) gemaakt. Steroid hormones are not stored in the endocrine cell, because of their lipophilic
nature. They are made on demand and diffuse out of the endocrine cell.